Vaccines For Humans

VACCINES
FOR HUMANS
PROJECT SYNOPSES
Research funded by
the European Union
Interested in European research?

Research*eu is our monthly magazine keeping you in touch with main developments (results, programmes, events, etc.).
It is available in English, French, German and Spanish. A free sample copy or free subscription can be obtained from:
European Commission
Directorate-General for Research
Communication Unit
B-1049 Brussels
Fax (32-2) 29-58220
E-mail: [email protected]
Internet: http://ec.europa.eu/research/research-eu
EUROPEAN COMMISSION
Directorate Health
Unit F3 - Infectious Diseases
http://ec.europa.eu/research/health/infectious-diseases/index_en.html
Contact: Ole Olesen
European Commission
Office CDMA 02/158
B-1049 Brussels
Tel. (32-2) 29-53999
Fax (32-2) 29-94561
EUROPEAN COMMISSION
VACCINES
FOR HUMANS
Research funded by
the European Union
2008
Directorate Health
EUROPE DIRECT is a service to help you find answers

to your questions about the European Union
Freephone number (*):
00 800 6 7 8 9 10 11
(*) Certain mobile telephone operators do not allow access to 00 800 numbers
or these calls may be billed
LEGAL NOTICE
Neither the European Commission nor any person acting on behalf of the Commission is responsible for the use which
might be made of the following information.
The views expressed in this publication are the sole responsibility of the author and do not necessarily reflect the views
of the European Commission.
A great deal of additional information on the European Union is available on the Internet.
It can be accessed through the Europa server (http://europa.eu).
Cataloguing data can be found at the end of this publication.
Luxembourg: Office for Official Publications of the European Communities, 2008
ISBN
DOI
978-92-79-09455-2
10.2777/84341
European Communities, 2008

Reproduction is authorised provided the source is acknowledged.
Printed in Belgium
Printed on white chlorine-free paper
Table of contents
Commissioners preface Introduction
14
HUMAN VACCINE RESEARCH IN THE EUROPEAN UNION
15
EUROPEAN VACCINE RESEARCH
Basic Vaccinology
18
Introduction
BASIC VACCINOLOGY
20
MUVAPRED
Mucosal Vaccines for Poverty-Related Diseases
24
EPIVAC
Development of a Multi-Step Improved Epidermis Specific Vaccine Candidate against HIV/AIDS
26
MuNanoVac
Mucosal Nano-Vaccine Candidate for HIV
28 CompuVac
Rational Design and Standardised Evaluation of Genetic Vaccines
30
BacAbs
Assessment of Structural Requirements in Complement-Mediated Bactericidal Events: Towards a Global

Approach to the Selection of New Vaccine Candidates
32
MICROBEARRAY
Genome Scale Analysis of the Immune Response against Pathogenic Micro-Organisms Leading
to Diagnostic and Vaccine Candidates and Development of an Integrated Micro Array Platform for Clinical Use
34 DEC-VAC
Development of a Dendritic Cell-Targeted Vaccine against AIDS
36 DC-VACC
Dendritic Cells as Natural Adjustments for Novel Vaccine Technologies
38 THERAVAC
Optimised delivery system for vaccines targeted to dendritic cells
40
AIDS-CoVAC
Generation of a Coronavirus-Based Multigene AIDS Vaccine and Evaluation in a Preclinical SIV Model
42
HIVAB
Generation of Broadly Cross-Neutralising Antibodies for Innovative Active-Passive

HIV Vaccination Strategies Based on Modified Ig-Gene Transgenic Mice
44
Highly Innovative Strategies for Vaccination to Poverty-Related Diseases
INNOVAC
46
ImmunoGrid
The European Virtual Human Immune System Project
48
VaccTIP
Vaccine Strategies for Combined Targeting of Innate and Adaptive Immune Pathways
50
MVACTOR
Host Immune Activation-Optimised Vaccinia Virus Vectors for Vaccine Development
Diseases Specific Vaccine Research

53
Introduction
DISEASE SPECIFIC VACCINE RESEARCH
56
AVIP
AIDS Vaccine Integrated Project
58 RMVHIV
Recombinant Measles Virus as a Vector for HIV Vaccines
60
AUTO/ALLO CELL-HIV
Development of a Novel Therapeutic HIV-1 Vaccine: Horizontal Gene Transfer

by Using Apoptotic HIV-1 DNA Containing Activated T Cells
62
Pox-gene
A Combined Pox-Virus/Lentiviral Vector System to Treat HIV Infection;

Immunisation and Direct In Vivo Gene Transfer in T-Lymphocytes
64
Allomicrovac
A Combined Microbicidal-Immunising Strategy Against SIV and HIV Infection
66
VIAV
Very Innovative AIDS Vaccine
68
HIV VIROSOMES
Development of a New Vaccine against HIV: Virosomes Incorporating HIV Proteins
70 TIP-VAC
Explaining and Improving Efficacy of Targeted Immunodeficiency Virus-like Particle Vaccines against AIDS
72
EPI-VAC
Identification of Novel Epitopes as HIV-1Vaccines Candidates
74
EMVDA
The European Malaria Vaccine Development Association
76
Preclinical Studies towards an Affordable, Safe and Efficacious Two-Component Paediatric Malaria Vaccine
PRIBOMAL
78 SME-Malaria
SME Led Malaria Vaccine Initiative
80
MALINV
Differential Expression of Malaria Invasion-Associated Proteins in the Porozoite: Novel Vaccination Strategy
82 TB-VAC
An Integrated Project for New Vaccines against Tuberculosis
86 Neotim
Innate and adaptive immunity in clinical and experimental mycobacterial infection in neonates and infants
88
Vaccines4TB
Genome - and HLA- Wide Scanning and Validation of Cytotoxic CD8 T Cell Responses
against Mycobacterium Tuberculosis
90
ImmunoVacTB
A New Approach for Developing a Less Immunosuppressive Vaccine for Tuberculosis
92
FLUVACC
Live Attenuated Replication-Defective Influenza Vaccine
94
FluVac
Dose Sparing and Increased Immunogenicity for Vaccination

against Pandemic Influenza with CoVaccine HT
96
PANFLUVAC
Efficacious Vaccine Formulation System for Prophylactic Control of Influenza Pandemics
98
Intranasal H5vaccine
Protective Efficacy of Intranasal del NS1 (H5N1) Influenza Vaccine
100 CHIMERIC VACCINES

del NS1 Virus as a Vector for Foreign Antigens
102
Universal Vaccine
Novel Antigen -Adjuvant Vehicle as an Effective Influenza Vaccine
104
HEPACIVAC
New Preventative and Therapeutic Hepatitis C Vaccines:From Preclinical to Phase I
106 DISSECT
Development of Intervention Strategies against SARS in a European-Chinese Taskforce
108 SARSVAC
Immunoprevention and Immunotherapy of SARS Infection
110 SARS/FLU VACCINE

Development of a Combined Influenza/SARS Vaccine
112 NOVADUCK
Novel AI DIVA Recombinant Vaccines for Duck
114
AIV VACC DIAGNOSIS
Vaccine, Diagnostic Test Development and Immunology Aspects of Avian nfluenza
116 SCOOTt
Sustainable Control of Onchocerciasis Today and Tomorrow
118 TRANCHI
T Cell Regulation and the Control of Helminth Infections
120
BOVAC
Development of a Prophylactic Vaccine and Diagnostic Markers to Diagnose

and Prevent Lyme Borreliosis Specific to Europe and North America
122 SAVINMUCOPATH
Novel Therapeutic and Prophylactic Strategies to Control Mucosal Infections
by South American Bacterial Strains
124 OMVac
Novel Prevention and Treatment Possibilities for Otitis Media
through the Comprehensive Identification of Antigenic Proteins
126
HEVAR
Herpesvirus-based Vaccines against Rotavirus Infections
128 SUPASALVAC
Salmonella-Free Broilers by Live Vaccine-Induced Innate Resistance to Colonisation
and Invasion and Novel Methods to Eliminate Vaccine and Field Strains
130 TRYPADVAC2
Development of an Anti-Disease Vaccine and Diagnostic Tests for African Trypanosomosis
132 CANCERIMMUNOTHERAPY
Cancer Immunology and Immunotherapy
134 DENDRITOPHAGES
Therapeutic Cancer Vaccines
136
LCVAC
New Vaccination Therapies for Lung Cancer
138
VITAL
Development of Optimised Recombinant Idiotypic Vaccines

for Subset-Specific Immunotherapy of B Cell Lymphomas
140
Alzheimers Disease-Treatment Targeting Truncated A40/42 by Active Immunisation
MimoVax
Clinical Research and capacity Building

144
Introduction
CLINICAL RESEARCH AND CAPACITY BUILDING
146
EDCTP
European and Developing Countries Clinical Trials Partnership
148
EUROPRISE
European Vaccines and Microbicides Enterprise
152 DC-THERA
Dendritic Cells for Novel Immunotherapies
154
ENACT
European Network for the Identification and Validation of Antigens and Biomarkers in Cancer and their
Application in Clinical Cancer Immunotherapy
156
ADVAC-EC
Advanced Vaccinology Training for Scientists from ACC and Developing Countries: From Genomics
to Vaccination Strategies for Communicable Diseases Linked to Poverty
158 NeutNet
Standardisation of HIV Neutralisation Assays to be Used in Vaccine Research and Clinical Trials
160 COINFECT
Malaria and Coinfection: New Insights for Malaria Control
162
EURHAVAC
European Network for Harmonisation of Malaria Vaccine Development
164
PAHPV-1
HPV Pilot Action Indonesia
166 REBAVAC
Novel Opportunities to Develop Vaccines to Control Antibiotic Resistant Bacteria:
from the Trials Back to the Laboratory
Commissioners preface
HUMAN VACCINE RESEARCH

IN THE EUROPEAN UNION
The use of vaccines is saving millions of lives every year,

and the tale of vaccines is one of the greatest success
stories in medical history. Vaccines were responsible for
the eradication of smallpox in 1970, the eminent eradication
of polio and possibly the future eradication of measles.
Vaccines can be thanked for millions of lives saved every
year from diseases such as tetanus, hepatitis, and flu, but
also for economic stability and development in countries
where diseases such as mumps, rubella and diphtheria
were previously responsible for millions of working hours
lost to sickness, disability and care of relatives.
The great success of vaccines in the past and present
should be used as inspiration to intensify research
in this area of life science even further. A number of
important infectious diseases such as HIV/AIDS, malaria
and hepatitis C are thus continuing to escape attempts
to produce effective vaccines against them. Vaccines
against a number of other infectious diseases such as
TB and influenza exist, but are only partially effective and
need dramatic improvement to respond to the real public
health needs. Furthermore, the emerging possibility of
preventing, treating or halting a range of non-infectious
diseases through vaccine approaches is one of the most
exciting frontiers in medical science, and it holds huge
potential to cover unmet medical needs in areas such as
cancer, autoimmune diseases and neurology.
Europe has a long and successful tradition of vaccine
research in both public and private institutions. Europe is
also home to many of the worlds oldest and largest vaccine
manufacturers. Europe is therefore well positioned to take
on new challenges in vaccine research, and exploit the
immense opportunities that are opening up in this field of
science. The Sixth Framework Programme (FP6), which
was adopted by the European Commission (EC) in 2002,
was an important catalyst in this direction and allocated
substantial support to European vaccine research. FP6
made it possible for the first time for the EC to support
large-scale multidisciplinary consortia with a focus on
translational research, while also supporting smaller
projects to explore highly innovative ideas and concepts.
10
The vast majority of vaccine and vaccinology activities

in FP6 was funded through the Health theme, although
important contributions came from the Food theme, the
Information Society theme (IST) and from cross-cutting
activities on international cooperation (INCO), and the
support activities to small and medium-sized enterprises
(COOP). Furthermore, vaccines for zoonotic diseases
were predominantly supported through the Food theme.
This publication compiles the projects on human vaccines
and vaccinology that have been supported through the
Sixth Framework Programme. By doing so, it provides
evidence of a vibrant, visionary and ambitious community
of European vaccine researchers. It also shows how
hundreds of scientists are working across Europe to
discover and develop new vaccines for the world. It goes
without saying that the European Commission will seek to
maintain Europes leading position in this important area
of research by providing continued support to vaccine
research throughout the Seventh Framework Programme
(2007-2013).
Janez Potonik
European Commissioner
in charge of Science and Research
introduction
EUROPEAN VACCINE
RESEARCH
Vaccine research has seen a remarkable renaissance

during the last decade. This has partly been catalysed
by scientific breakthroughs such as the full genome
sequences of several infectious pathogens, and refined
knowledge about the immune system and its response
mechanisms. The other major factor has been a significant
influx of money from public funding bodies, private charity
organisations and commercial enterprises. In the private
sector, recent commercial successes such as the human
papilloma virus (HPV) vaccine have triggered small
and even large pharmaceutical companies to initiate or
renew their interest in vaccines. This trend has been
further supported by the appearance of novel financing
mechanisms such as Product Development Partnerships
(PDPs), and the introduction of market-related incentives
such as the Vaccine Fund, the Advanced Market
Commitment (AMC) and the International Financing
Facility for vaccines.
There are several reasons for the European public sector
to engage actively in vaccine research and to support
the development of new effective vaccines. Firstly,
vaccines are one of the most effective ways to protect
people against infectious diseases and thereby actively
promote better health and quality of life, locally as well
as globally. Secondly, vaccines are one of the most costeffective measures for public health. Safe and effective
prophylactic vaccines are significantly more cost effective
than repeated applications of drugs and other treatments.
Vaccines can thereby release health sector cash, which
can instead be used elsewhere in the health system.
Thirdly, the development of vaccines against extraordinary
pathogens such as HIV may be so technically and
scientifically challenging that it may never occur without

sustained support and active contribution from the public
sector. Addressing very challenging pathogens may, on the
other hand, lead to scientific breakthroughs with a broader
application to technological and economic development.
Last but not least, vaccines against pathogens such as
dengue or malaria, that are mainly (or only) prevalent in
low-income countries, are unlikely to be developed unless
the public sector subsidises and supports research. In this
respect, international public organisations such as the
European Commission have a particularly important role to
play as they can act with a higher emphasis on the global
health agenda rather than national research priorities.
During the course of FP6, the European Commission has
supported a wide variety of vaccine research activities
with relevance for human health. Taken together, more
than EUR 410 million was allocated to research projects
with focus on vaccines or projects with relevance to
vaccines or vaccinology aspects. Broadly speaking, three
different types of vaccine research have been funded
(Fig 1): new, innovative approaches to vaccinology and
vaccine development have been funded with a view to
develop and mature highly innovative technologies and
vaccinology concepts. In this area of activity, the EC has
funded 15 projects with more than EUR 46 million in
total. Most projects, namely 42, were funded in disease
specific vaccine research. This resulted in a total EC
contribution of EUR 136 million. In budgetary terms, the
largest supported area was clinical vaccine research
and capacity building, which received a total of EUR 230
million. It should be noted that this figure includes an
EC contribution of EUR 200 million to the European and
Clinical
Research
and capacity
building
Basic Vaccinology
Disease specific
vaccine research
Number of projects
15
42
10
67
Total EC contribution
(million euros)
47
134
229
410
TOTAL
Fig. 1: Overview of EC funded human vaccine research in FP6

11
Developing Countries Clinical Trials Partnership (EDCTP)

initiative. The EDCTP initiative is an independent legal
entity that supports capacity building and clinical trials of
new vaccines and treatments for HIV/AIDS, malaria and
TB in sub-Saharan Africa. Only a part of the total EDCTP
activities are therefore dedicated to vaccine research and
vaccine related activities, albeit an important and crucial
part. Other activities supported in the area of clinical
research have focused on increasing the knowledge and
efficacy of existing vaccines.
Different magnitudes of projects have been supported
within each category. Large Integrated Projects (IP)
have been used to support multi-disciplinary consortia
with sufficient critical mass to translate basic research
results into applications. Smaller and focused research
activities have been supported using Specific Targeted
Research Projects (STREP). This instrument has typically
been used to develop innovative concepts or discovery
of new vaccine candidates. Networks of Excellence
(NoE) and coordination actions (CA) have been used to
structure and organise the European research community
around common research agendas. Strategic Support
Actions (SSA) have been used to support small, targeted
supporting activities such as conferences, workshops or
training activities.
The vast number of projects were STREPs, which constitute more than two thirds of all projects (Fig. 2). However,
it is the IPs that form the core of the EC funding pipeline.
Due to their large size and critical mass of multidisciplinary
participants, the IPs may act as uptake of new discoveries
from smaller, innovative projects, while delivering matured
project results in the other end for clinical applications or
further downstream development by industry organisations, the EDCTP, or public-private partnerships.
The EC believes that tighter collaboration between
multiple stakeholders is central to the advancement of
health science. A key component of the EC Framework
programme is therefore to promote cooperation between
researchers in different countries, and across sectors and
disciplines. While undertaking major research activities,
these partnerships are also contributing to a long-term restructuring of the European research community.
During FP6, a total of 575 research groups participated
in human vaccine research projects (Fig. 3). The vast
majority was located in EU Member States (84%), but
increasing globalisation in health science means that more
and more participants come from other countries, either
European non Member States (7%) or non European
countries (9%).
EDCTP
IP
STREP
NoE
SSA
10
46
Number of participants
16
163
319
79
27
Total EC contribution
(million euros)
200
103
80
24.5
2.8
Number of projects
Fig. 2: Overview of instruments used for funding vaccine research in FP6
12
COUNTRY NAME
1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 2 2 2 2 2 2 2 3 3 3 3 4 4 4 4 4 4 4 5 5 6 7 10 12 19 28 30 33 34 47 62 74 78 80
NUMBER OF PARTNERS
Fig. 3: Participants in EC funded human vaccine research in FP6 come from a large number of different countries.
13
Significant efforts were also made to build partnerships

between scientists in different sectors. The result has
been that more industry partners have participated in
vaccine research projects in FP6 than in any previous
framework programme. The industry partners include
small and medium-sized enterprises (SMEs) as well as
large and established vaccine companies. In total, more
than 10% of all partners in the EC funded vaccine projects
came from the private industry sector.
At the beginning of 2007, FP6 was followed up by the
introduction of the Seventh Framework Programme
(FP7), in which Health research plays an equally
important role as in FP6, and with an even higher
average annual budget. FP7 runs from 2007 to 2013, and
has a budget allocation of EUR 6 billion to cooperative
Health research, corresponding to an annual average
of approximately EUR 900 million. The objective of this
programme is to support a wide range of top-quality
research activities in transnational cooperation across
Europe and increasingly globally.
Activities in poverty-related diseases (HIV/AIDS, malaria,
TB) remain a key activity in FP7, but the area of infectious
diseases has been strengthened by including two new
dedicated activity areas for Emerging Infectious Epidemics
and Neglected Infectious Diseases. Emerging Infectious
Epidemics will fund research on upcoming threats from
emerging viral infections to European health, while
activities in Neglected Infectious Diseases will address a
range of protozoan, bacterial and helminth infections of
significant importance to global health in resource poor
countries. FP7 will continue to support research in basic
vaccinology in both infectious and non-infectious diseases,
primarily through pillar I of the Health programme, which
is dedicated to Biotechnology, Generic Tools and Medical
Technologies for Human Health. Last but not least,
FP7 will also provide continued support to research in
a range of non-infectious diseases, for example cancer,
neurodegeneration and autoimmune diseases, where
vaccine approaches are becoming increasingly relevant.
14
The European vaccine research in FP6 is pointing

towards the creation of a new, promising patchwork of
collaboration within the vaccine research community
across Europe and beyond. The focus on translational
research in the health theme of FP7 makes it feasible
to accelerate European vaccine research even further,
and translate the most promising results into application.
FP7 is thus well equipped to provide sustained support to
the wide range of successful vaccine research that was
initiated in FP6.
OLE F. OLESEN
Acknowledgements: This publication was compiled by Ole F. Olesen and Rachida Ghalouci with the assistance of colleagues in DG RTD of the
European Commission, and with the invaluable help of friends and collaborators in the European vaccine research community. Special thanks
go to Alain Vanvossel (Head of Infectious Diseases), Anna Lonnroth (Deputy Head of Infectious Diseases) and Bernard Mulligan (Deputy Head
of Genomics and Systems Biology) for sustained support to compile this catalogue. Similarly, our thanks go to Virginie Braconnier and Evelyne
Bastin for secretarial assistance, and to Yiannos Contrafouris for technical and editorial support.
15
Basic Vaccinology
Introduction
BASIC VACCINOLOGY
Vaccine research has come a long way in the past 20 years,

with technological break-throughs that are paving the way
for innovative and more efficacious vaccines against a host
of pathogens and pathologies. The application of modern
biological technologies and advances in our understanding
of genomic knowledge has resulted in new concepts like
reverse vaccinology, DNA vaccines, recombinant subunit
vaccines and non-replicating vectors. Many of these
new concepts are now being applied around the world to
specific diseases and pathogens, and some have already
progressed to advanced clinical trials and new products
such as the meningococcal vaccine and hepatitis B vaccine.
Recent years have also seen significant advances in our
understanding of the control mechanisms of the immune
system, as well as the mechanisms underlying both acquired
and innate immunity. Yet, a further understanding of basic
mechanisms in the immune system is needed to fully exploit
the immense possibilities of modern vaccinology.
Research Area
Project Acronym
MUVAPRED
Topical vaccinology
Genomic Vaccinology
Dendritic cells
Explorative vaccinology
The 15 EC funded projects have addressed a wide

variety of important aspects in basic vaccinology (Table
1), although 3 activity areas have received particular
attention, namely mucosal vaccinology; post-genomic
vaccinology and dendritic cells as vaccine targets.
EC Contribution
Number of Partners
15.250.000
29
EPIVAC
2.400.000
MuNanoVac
1.505.702
CompuVac
7.969.442
15
BacAbs
2.269.999
MICROBEARRAY
1.401.002
DEC VAC
3.400.000
10
DC-VACC
2.000.000
THERAVAC
2.267.000
AIDS-CoVAC
958.000
HIVAB
950.000
INNOVAC
2.000.000
ImmunoGrid
1.950.000
VaccTIP
1.000.000
MVACTOR
1.000.000
Table 1: EC-funded projects in basic vaccinology

18
Many researchers are contributing to this exploration of

the human immune response, which eventually could enable the development of future vaccines against some of
the most challenging pathogens and diseases. The EC
has participated in the global efforts to a better understanding of basic vaccinology by allocating almost EUR
50 million to research in this area. The funding has been
shared between 15 research consortia, all of which are
focused on knowledge and technologies with broader relevance for vaccine development.
Many infectious diseases are caused by pathogens that

enter the human body through mucosal surfaces. This
includes such prominent diseases as HIV/AIDS, TB,
influenza and sexually transmitted diseases. Many of
these diseases could be better confronted if the causing
pathogen could be stopped at the first port of entry to the
human body. This requires a detailed understanding of
the delicate interplay between antigens and adjuvants
during mucosal immunisation as well as an understanding
of the relationship between the systemic and mucosal
immune system. Two EC funded projects are addressing
this, namely the MUVAPRED integrated project, which
explores how an effective and lasting immune response
can be induced at mucosal surfaces, and the MuNanoVac
STREP project, which explores the possibility of using
nanoparticles as a vehicle for mucosal immunisation. A
related project, EPI-VAC, addresses local immunology,
and is focused on transdermal immunisation with DNA
vaccines. Taken together, more than EUR 19 million has
been allocated to research activities on mucosal and/or
local immunology. This corresponds to 40% of the total
EC contribution to basic vaccinology, and confirms the
importance of this area within the EC portfolio of vaccine
research activities.
Another key area of research has been the use of new
genomic data for better selection of new vaccine candidates.
This is the core activity of the Compuvac project, which
gathers 15 partners in a joint effort to develop a platform
for Rational Design and Standardised Evaluation of
Genetic Vaccines. BACABS is a STREP project which
focuses on establishing a standard approach for selection
of vaccine candidates, mainly on the basis of structural
determinants. Together with Microbearray, another project
in this category, these projects have received a total EC
funding of more than EUR 11 million, corresponding to
approximately 25% of the funding to basic vaccinology.
challenging area of vaccinology. The ability to induce a

controlled immune response against endogenous proteins
that are present in abnormal amounts or conformations
could be the key to the development of prophylactic or
therapeutic vaccines for a wide range of diseases such
as AIDS, cancer, autoimmune diseases and degenerative
diseases. Most of the current vaccines work by inducing
an antibody response, but using vaccines against many
types of diseases, infectious as well as non-infectious,
may require a concurrent induction of a cytotoxic T-cell
response. To achieve this, a better understanding of the
role of dendritic cells in the immune system is necessary.
The project DEC-VAC aims to enhance antigen uptake,
and presentation by dendritic cells (DCs) of either protein
vaccines, peptide vaccines, DNA vaccines or viral vector
vaccines, thus providing a broad vaccination platform. The
two STREP projects DC-VACC and Thera-vac explore the
potential future use of dendritic cells as natural adjuvants
and targets for a broad range of vaccines.
Other areas of basic vaccinology have been supported
by the EC through a number of STREP projects.
These projects have explored a wide variety of vaccine
research, ranging from the use of new vectors for vaccine
development (MVACTOR), the development of new
vaccine strategies for both innate and adaptive immune
responses (VaccTip) to the establishment of a virtual
immune system (Immunogrid).
The projects on basic vaccinology are thus covering a
wide range of activities. They are opening new avenues for
vaccine development, and by establishing new methods
and introducing novel technologies they are creating the
toolbox of future vaccine research. Albeit that many of
the projects are highly risky, they are also associated with
a high potential impact on vaccine development that may
be applied across a range of diseases.
The third major area of funding for basic vaccinology is the

potential utilization of dendritic cells for various vaccine
approaches against both infectious and non-communicable
diseases, including cancer. This is an exciting, but also
19
MUVAPRED
Acronym: MUVAPRED
Project number: LSHP-CT-2003-503240
EC contribution: 15 250 000
Mucosal Vaccines
for Poverty-Related
Diseases
Duration: 60 months
Type: IP
Starting date: 1 December 2003
Project website: www.mucosalimmunity.org/
muvapred
BACKGROUND
AIMS
HIV/AIDS and TB have caused an unprecedented global

health crisis, accounting for more than 4 million deaths each
year, with the majority of these in developing countries,
particularly sub-Saharan Africa. Since the start of the HIV
epidemic, 21million people have died and 57 million people
have become infected. Mycobacterium tuberculosis affects
one third of the worlds population and represents the main
cause of death in HIV-infected patients. Furthermore, TB
represents a dramatic problem in eastern Europe because
it is highly drug-resistant. This epidemiological situation
is a major problem for all of Europe, due to the impact
of the spread of clinically relevant strains (World Health
Organization report, 2002).
Human Immunodeficiency Virus and Mycobacterium

tuberculosis enter the human body at mucosal sites. This
Integrated Project aims to develop mucosally delivered
vaccines against HIV and TB, which will induce local
immunity able to neutralise the pathogens at their port of
entry, and systemic immunity able to prevent the systemic
spread of the infection. The possible development of mucosal
vaccines against malaria is also being investigated.
No vaccines have been developed for HIV yet, and the

efficacy of the BCG vaccine currently being used in
different populations and regions ranges from 0% to 80%.
Despite this, vaccination is one of the most cost-effective
interventions; the economic value associated with vaccines
(mainly those for developing countries) is negligible.
Most existing vaccines are still administered by systemic
injection. Although widely accepted, parenteral vaccination
has potential drawbacks. Most of the pathogens invade
their human hosts at the level of the mucosal surfaces,
which represent the very first antimicrobial barrier through
non-specific (anatomical) and specific (immune) defence
mechanisms. Mucosal vaccination would offer several
advantages over the parenteral route of vaccination.
Inducing local microbial-specific immune responses would
block pathogens at the port of entry, thus increasing the
general efficacy of the vaccine. By avoiding the traumatic
procedure of injection, mucosal vaccination would increase
compliance and consequently coverage. It would also
facilitate vaccine delivery, especially in poorer countries,
and would significantly decrease the risk of infectious
agents spreading via contaminated syringes.
20
In the project existing antigens, which are known to be

protective in animal models against HIV and TB, are being
formulated for mucosal delivery and tested in clinical trials.
The antigens used for the initial clinical trials are the latest
generation of the envelope protein of HIV, which, being
deleted from loop 2, unmasks some of the conserved
epitopes and induces broadly neutralising antibodies
against primary isolates of HIV and the fusion protein of
Ag85B and ESAT-6 of TB.
While the first trials are being performed, new systems
to deliver mucosal vaccines and basic mechanisms of
mucosal immune responses and memory in humans are
being studied. This will allow a better understanding of
the clinical results, and optimisation of second-generation
vaccines to be tested in developing countries. The projects
intention is to provide candidate mucosal vaccines against
HIV and TB that could subsequently enter the path
towards licensure through phase II and III clinical trials in
developing countries.
EXPECTED AND OBTAINED RESULTS

MUVAPRED has targeted the clinical demonstration
of safety and immunogenicity in healthy volunteers of
vaccine candidates against HIV and TB infections. The
results will advance safe and powerful mucosal vaccines
in efficacy trials in developing countries.
21
Project Coordinator:
Rino Rappuoli
Rino Rappuoli
Chiron S.r.l.
Via Fiorentina 1
Siena, Italy
Tel: +39-0 57 72 43 414
Email: [email protected]
Partners:
Gordon Dougan
Microbial Pathogenesis
(Team 15: Wellcome Trust Sanger Institute)
Cambridge, England
UK
Jan Holmgren
Gteborg University
Gteborg, Sweden
Nils Lycke
Gteborg University
Gteborg, Sweden
Brigitte Gicquel
Institut Pasteur
Unit de Gntique Mycobacterienne
Paris, France
Nathalie Winter
Institut Pasteur
Unit de Gntique Mycobacterienne
Paris, France
Gianni Pozzi and Donata Medaglini
Universit di Siena
Siena, Italy
Stefan H.E. Kaufmann
Max Planck Institute for Infection Biology
Berlin, Germany
Barbara Ensoli
Istituto Superiore di Sanit
Rome, Italy
Antionio Cassone
Rome, Italy
Antonio Lanzavecchia
Institute for Research in Biomedicine (IRB)
Bellinzona, Switzerland
22
Paul Racz
Bernhard-Nocht-Institute for Tropical Medicine
Hamburg, Germany
Thomas Lehner
Kings College
London, England
UK
Kingston Mills
Trinity College
Immune Regulation Research Laboratory
Dublin, Ireland
Peter Andersen
Statens Serum Institute
Copenhagen, Denmark
Francesco Dieli
Consiglio Nazionale delle Ricerche
Istituto di Biomedicina e Immunologia Molecolare
Palermo, Italy
Alberto Mantovani and Mario Negri
Istituto di Ricerche Farmacologiche
Milan, Italy
Andreas Radbruch
German Arthritis Research Centre
Berlin, Germany
David Lewis
St Georges Hospital Medical School
London, England
UK
Peter Sebo
Academy of Sciences of the Czech Republic
Prague, Czech Republic
Gianfranco Del Prete

University of Florence
Dip. Medicina Interna
Florence, Italy
Oumou Younoussa Sow
Service de Pneumo-Phtisiologie
Conakry, Republic of Guinea
Giampietro Corradin
University of Lausanne
Epalinges, Switzerland
Aldo Tagliabue
Alta S.r.l.
Siena, Italy
Mahavir Singh
LIONEX Diagnostic and Therapeutics GmbH
Braunschweig, Germany
Christoph Heinzen
INOTECH AG
Dottikon, Switzerland
Howard Engers
The Armauer Hansen Research Institute (AHRI)
Addis Ababa, Ethiopia
Gita Ramjee
South African Research Council
Westville, South Africa
Philip Marsh
Health Protection Agency
Salisbury, England
UK
23
EPIVAC
Acronym: EPIVAC
Development of a MultiStep Improved Epidermis

Specific Vaccine Candidate
against HIV/AIDS

Duration: 36 months
Type: STREP
Starting date: 1 January 2007
Project website: www.fitbiotech.com
BACKGROUND
More than 40 million people worldwide are currently

infected with HIV1. Most of those are from developing
countries where there is an urgent need for efficient
vaccine candidates. The HIV virus induces chronic
infection in patients, eventually leading to deterioration of
the immune system and the onset of immune deficiency.
The right vaccine will be capable of inducing cell-mediated
and humoral immunity against the virus and virally infected
cells in different phases of the viral life cycle. This could
be carried out by DNA vaccines if they can be made
more efficient. Different technologies will be used to try
to achieve this including the restricted expression of the
multi-epitope/multivalent HIV antigens in specific cells of
the epidermis; a micro-needle array-based infection device
for reproducible and efficient delivery into the epidermis;
and the adjuvant effect of different cytokines.
The expected results of the project are listed below:
AIMS
EPIVAC aims to generate an effective and affordable DNAbased preventative and therapeutic vaccine against HIV.
The first goal is the development of a reliable, reproducible
and robust delivery system. The plasmids and genes used
in these studies will allow for the quantitative evaluation of
the efficiency and kinetics of delivery of plasmid DNA into
the epidermis and epidermal cells.
The second goal of the project is to analyse the effect on
the nature and extent of the induced immune response
by different HIV1 antigen expression in different cells of
the epidermis.
24
New devices and methodologies for DNA delivery

to the epidermis.
The generation of improved DNA-based vaccines.
The generation of new proprietary HIV antigens
based on the EPIVAC optimised vector.
Ioana Stanescu
FIT Biotech Plc

Biokatu 8, 33520
Tampere, Finland
www.fitbiotech.com
Partners:
Henrik Hellqvist
Silex Microsystems AB
Jrflla 595, Sweden
Evgeny Berik
Estla Ltd
Tartu, Estonia
Charlotte Dalba
EPIXIS SA
Paris, France
David Klatzmann
University of Pierre and Marie Curie
Paris, France
Mart Ustav
Tartu University Institute of Technology
Tartu, Estonia
Roger Le Grand
French Atomic Energy Commission
Paris, France
25
MuNanoVac
Acronym: MuNanoVac
Mucosal Nano-Vaccine
Candidate for HIV

Duration: 36 months
Type: STREP
Project website:
BACKGROUND
There are many infectious diseases for which no vaccines

are available, and there is no candidate that allows
efficient T cell and B cell immune responses. In the case
of HIV-1 mediated infection it is believed that both arms
of the immune response (humoral and cellular) should
be stimulated by any potential vaccine candidate. Recent
data on natural primary HIV-1 infection has established
that the spreading of the virus in the mucosa is essential
for infection to take place. Therefore, every vaccination
strategy should be able to elicit a strong mucosal immunity
at the potential sites of contamination, and prevent
spreading of HIV-1 virions.
MuNanoVac will contribute towards the following:
AIMS
The MuNanoVac project will assess a new vaccine strategy
to prevent HIV-1 infection based on a biodegradable
synthetic colloidal carrier made of polylactic acid (PLA)
nanoparticles covered with absorbed antigens. Such
nanoparticle-based vaccine carriers allow targeting of
dentritic cells or the transportation of the vaccine through
skin or mucosal epithelial barriers. To amplify the mucosal
immune response, the project will investigate the potential
use of immunomodulator molecules co-adsorbed with
HIV antigens onto PLA particles and will compare two
different immunisation routes, mucosal or sub cutaneous,
in different animal models.After selection of the best
route of immunization associated with the more potent
immunomodulatory molecules, two HIV-l antigens,
trimeric gp140 (clade C) and p24 will be formulated onto
PLA particles for assessing its efficacy as an HIV vaccine
in non human primates.
MuNanoVac wants to demonstrate evidence that a
strong and persistent mucosal immune response for a
given antigen can be reached, using biocompatible PLA
nanoparticles as a versatile vaccine vehicle.
26
www.munanovac.eu
bringing new knowledge and innovative

technologies through the HIV vaccine discovery
process;
proposing new vaccine candidates using
biodegradable synthetic colloidal carrier for
combating and preventing HIV/AIDS.
In addition, the projects results will be used as a basis for
developing biodegradable vaccine candidates for other
poverty-related diseases.
Project Coordinators:
Jacqueline Huet
PHUSIS
Saint Ismier, France
Tel: +33-4 76 52 51 60
Bernard Verrier
Centre National de la Recherche Scientifique

Lyon, France
Tel: +33-4 72 72 26 36
Partners:
Robin Shattock
London, England
UK
Teresa Gallart
Hospital Clnic de Barcelona
Barcelona, Spain
Roger Le Grand
Commissariat lEnergie Atomique
Paris, France
Milan Raska
Palack University
Olomouc, Czech Republic
Behazine Combardiere
Universit Pierre et Marie Curie
Paris, France
Ulrike Blume-Peytavi
Charit Universittsmedizin Berlin
Berlin, Germany
27
CompuVac
Acronym: CompuVac
Rational Design and

Standardised Evaluation
of Genetic Vaccines
Project number: LSHB-CT-2004-005246

Duration: 48 months
Type: IP
BACKGROUND
Recombinant viral vectors and virus-like particles are considered the most promising vehicles to deliver antigens in
prophylactic and therapeutic vaccines against infectious
diseases and cancer. Several potential vaccine designs exist but their cost-effective development lacks a standardised
evaluation system.
We have now assembled a unique set of vaccines of different class, from viral vector derived vaccines to inert VLPs,
analysed their efficacy with standardised methodologies,
and compared them with an intelligent database. This has
already allowed us to make significant comparisons between different vaccine types and to initiate novel vaccine
design and vaccination regimen. We are now evaluating
prime-boost immunisation regimen with these vectors. We
believe that this should have a significant impact on vaccine development, and notably for those vaccines requiring
prime/boost immunizations.
AIMS
CompuVacs main objective is to set up a standardised approach for the rational development of genetic vaccines.
The process comprises the development of:
a large panel of vaccine vectors representing
various vector platforms and all expressing the
same model antigens;
standardized methodologies for the evaluation of Tand B-cell responses and of molecular signatures
relevant to safety and efficacy;
a database for data storage and analysis of large
data sets;
intelligent algorithms for the rational development
of prime boost vaccination. One of our final goals
is to generate and make available to the scientific
community a tool box and an interactive
database allowing the comparative assessment of
future vaccines. We also aim to validate these tools
by the rationale development of preventive and/or
therapeutic vaccines against HCV.
A secondary objective is to apply these vectors, tools
and methods to the development of a preventive and/
or therapeutic vaccine against the hepatitis C virus
(HCV) incorporating one or more of the platform vectors
expressing the HCV envelope protein.
28
As end products, the vector platform and gold standard tools,

methods and algorithms will be available to the scientific
and industrial communities as a toolbox and interactive
database whose standardised nature should contribute to
cost-effective development of novel vaccines.
Prof. David Klatzmann
Centre National de la Recherche

Scientifique and Universit Pierre et Marie Curie
Paris, France
Tel: +33-14 21 77 461
E-Mail : [email protected]
Partners:
Dr Anatoly Sharipo
ASLA Biotech Ltd
Riga, Latvia
Prof. Jacek Blazewicz
Poznan University of Technology
Poznan, Poland
Prof. Thomas Brocker
Institute of Immunology - Ludwig-MaximiliansUniversitt Mnchen
Munich, Germany
Dr Franois-Loc Cosset
Institut National de la Sant et
de la Recherche Mdicale
Lyon, France
Dr Stefan Kochanek
Universittsklinikum Ulm
Ulm, Germany
Dr Penelope Mavromara
Hellenic Pasteur Institute

Athens, Greece
Prof. Albertus Osterhaus

Erasmus MC Rotterdam
Rotterdam, Netherlands
Prof. Paul Pumpens
BioMedical Research and Study Center
Riga, Latvia
Dr Kestutis Sasnauskas
Institute of Biotechnology
Vilnius, Lithuania
Prof. Rudolf Martin Zinkernagel
University of Zurich
Zurich, Switzerland
Dr Anne-Lise Williamson
University of Cape Town
Cape Town, South-Africa
Dr Gary Thomas Jennings

Cytos Biotechnology AG
Zurich, Switzerland
Dr Frdric Tangy
Institut Pasteur
Paris, France
Prof. Tina Dalianis

Karolinska Institutet
Stockholm, Sweden
Dr Albert Osterhaus
Rotterdam, The Netherlands.
Dr Charlotte Dalba
Epixis SA
Paris, France
Dr Alberto Epstein
Universit Claude Bernard Lyon 1
Villeurbanne, France
29
BacAbs
Assessment of Structural
Requirements in
Complement-Mediated
Bactericidal Events:
Towards a Global
Approach to the Selection
of New Vaccine Candidates
BACKGROUND
High throughput cloning and expression of large sets
of genomic ORFs (open reading frames) has become a
preferred industrial strategy for genome-wide searches
of new vaccine candidates. For invasive infections in
particular, the aim is to find proteins eliciting antibodies
capable of binding to the bacterial cell surface and, through
interaction with the complement system, effectively kill the
bacteria. However, current data accumulating from reverse
vaccinology studies indicate that only a small fraction of
surface-exposed proteins appears to elicit antibodies with
bactericidal activity.
Using information generated by reverse vaccinology
projects the project will apply a novel multidisciplinary
approach in identifying the structural requirements
for viable bactericidal vaccine candidates, developing
bioinformatics tools to predict compliance with such
structural requirements. Therefore, a systematic analysis
of sequence, structure, dynamics and interactions of
selected protein targets will be undertaken; serogroup-B
Neisseria meningitidis, a pathogen causing septicemia
and meningitis, for which no effective vaccine exists, will
be used as main model system.
AIMS
The aim of the project is to develop a strategy and
tools to identify early in the vaccine development
process those antigens that could induce production of
bactericidal antibodies. To achieve this goal, the project is
investigating the requirements for productive Ag-Ab-C1q
complex formation, and is taking a multidisciplinary and
comparative approach in studying the structural properties
of a number of these complexes. The MenB vaccine
development project of Novartis Vaccines & Diagnostics
is being taken as a model and a source for useful data and
reagent molecules.
30
Acronym: BacAbs
Duration: 36 months
Type: STREP
Project website: www.bacabs.org

Structural information on a set of proteins that are
components of the cell surface of major human
pathogens
Experimental protocols, bioinformatics tools and
databases to assist antigen selection
A framework in which integrated experimental and
in silico methods for the study of macromolecular
recognition can be further developed
A web-based technological platform integrating the
knowledge generated within the project and public
external data relevant to vaccine development
Additional information, including updates on project
results, may be obtained from the Project website:
Xavier Daura
Universitat Autnoma de Barcelona

Bellaterra, Spain
Tel: +34-9 35 81 28 05
E-Mail: [email protected]
Partners:
Guido Grandi
Novartis Vaccines and Diagnostics
Siena, Italy
Anatoly Sharipo
ASLA BIOTECH
Riga, Latvia
Etienne Lhermite
Bio-Xtal
Mundolsheim, France
Giorgio Colombo
Milan, Italy
Martin Zacharias
International University Bremen
Bremen, Germany
Martino Bolognesi
Universit degli Studi di Milano
Milan, Italy
Alexandre M J J Bonvin
Universiteit Utrecht
Utrecht, Netherlands
Jos Manuel Mas Benavente
INFOCIENCIA SL
Barcelona, Spain
31
MICROBEARRAY
Genome Scale Analysis of
the Immune Response against
Pathogenic Micro-Organisms
Leading to Diagnostic
and Vaccine Candidates
and Development of an
Integrated Micro Array
Platform for Clinical Use
Project number: COOP-CT-2004-508399

Duration: 24 months
Type: NoE
Starting date: 21 June 2004
BACKGROUND
The genome sequences of microbial organisms respon

sible for diseases of worldwide medical importance have
either already been sequenced or will be available in the
near future. Technologies for producing large numbers of
proteins have been developed and high-throughput assays,
such as protein microarrays, have been clinically validated
for detecting the presence of antibodies, in serum, directed
against microbial antigens. These achievements provide
the research sector with the opportunity to investigate the
natural immune response against the whole proteome of
a variety of micro-organisms. Powerful combinations of
genomic information, molecular tools and immunological
assays are becoming available to help identify the
antigens that function as targets of protective immunity, or
that could be used as markers for serodiagnosis.
This project significantly expanded the SMEs bank of

Intellectual Property and contributed to expertise within the
RTD sector. It is anticipated that the proposed work in high
throughput protein expression, software analysis, surface
peptides synthesis, protein and peptide surface capture,
and array reader instrumentation will create an integrated
platform of great commercial and research value. Finally,
MICROBEARRAY has contributed to unravelling how the
humoral immune response interacts with the microbial
proteomes, thus filling the gap between genomic data and
development of novel vaccines and diagnostic tools.
AIMS
The project aimed to identify in micro-organisms of great
medical relevance (M. pneumoniae, C. pneumoniae, L.
pneumophila, coronavirus spp and P. falciparum) a large
collection of surface and secreted proteins, as well as
putative endotoxins. This protein repertoire was produced
as recombinant molecules or as sets of overlapping
synthetic peptides, and printed on array slides. The serum
reactivity of groups of individuals with a proven history of
exposure to the selected micro-organisms was analysed
against the arrayed proteins, to identify diagnostic markers
and correlates of protection.
32
Acronym: MICROBEARRAY
Andrea Crisanti
Universita degli Studi di Perugia

Perugia, Italy
Tel +39-0 75 58 57 409
Partners:
Leszek Rychlewski
Bioinformatics Laboratory
Poznan, Poland
Antonio Cassone
Instituto Superiore di Sanita
Rome, Italy
John Attridge
Chelsea Instruments Ltd
London, England
UK
Franck Breitling
Deutsches Krebsforschungszentrum
Stiftung Des Oeffentlichen Rechts
Heidelberg, Germany
Diagnostic Matrices Ltd
London, England
UK
Kevin Bryne
Mikura Ltd
Sussex, England
UK
Vincent Monchois
ProteineXpert
Grenoble, France
Microtest Matrices Ltd
London, England
UK
33
DEC-VAC
Acronym: DEC-VAC
Development of a
Dendritic Cell-Targeted
Vaccine against AIDS

Duration: 48 months
Type: IP
Project website: www.rubr-uni-bochum.de
BACKGROUND
Vaccines targeting dendritic cells (DCs) have been the

topic of intense research on an international basis. The role
of DC in virus-specific cellular immunity in HIV infection
is particularly important, given the lack of neutralising
antibody activity in AIDS patients. It is therefore likely
that a DC-based anti-HIV vaccine could prove particularly
efficacious against HIV/AIDS.
Given the striking positive results in rodent models, this

strategy certainly has the potential to be effective and to
confront the global emergency caused by the spreading
HIV epidemic. Results from this research effort could lead
to the development of a prophylactic or therapeutic HIV/
AIDS vaccine. The DC-targeted vaccine approach could
also be useful for the development of vaccines against
other infectious diseases and cancer.
AIMS
The project aims to develop an innovative anti-HIV vaccine
able to enhance uptake and presentation of antigens by
dendritic cells (DCs). The projects strategy to enhance
antigen uptake and presentation by DCs can be applied
to protein vaccines, peptide vaccines, DNA vaccines and
viral vector vaccines, thus providing a broad vaccination
platform. Providing a novel HIV vaccine strategy for
safety and efficacy studies in humans by the end of the
project is an important aim. Therefore, the scientific and
technological objectives are to determine the following for
DC-targeted protein, DNA, and viral vector vaccines:

the DC targeting efficacy;

the immunogenicity;
the efficacy of different adjuvants;
the protective properties in the HIV-1/MuLV and SIV
macaque model.
Based on these results, the mechanisms of protection are

being investigated.
34
Klaus berla
Ruhr-Universat
Bochum, Germany
Partners:
Ralph Steinman
Rockefeller University
New York, USA
Britta Wahren
Swedish Institute for Infectious Disease Control
Stockholm, Sweden
Christiane Stahl-Hennig
Deutsches Primatenzentrum
Gttingen, Germany
Ralf Ignatius
Abt. Med. Mikrobiologie u. Infektionsimmunologie
Berlin, Germany
Paul Racz
Hamburg, Germany
Mariagrazia Uggucioni
Institute for Research in Biomedicine
Ralf Wagner
Geneart GmbH
Regensburg, Germany
Heribert Stoiber
Innsbruck Medical University
Innsbruck, Austria
Lazare Kaptue
University of Yaounde I
Cameroon, Africa
35
DC-VACC
Acronym: DC-VACC
Dendritic Cells
as Natural Adjustments
for Novel Vaccine
Technologies

Duration: 36 months
Type: STREP
Project website: www.biopolo.it/
BACKGROUND
The immune system of vertebrate animals has evolved
to respond to different types of perturbations, such as
pathogens, whilst limiting self-tissue damage. Initiation of
the immune response is accomplished by unique antigenpresenting cells, called dendritic cells (DCs) that rest until
encountering foreign microorganisms or inflammatory
stimuli. Early-activated DCs trigger innate immune
responses that represent the first line of defence against
invading pathogens. Activated DCs subsequently prime
antigen-specific immune responses, clearing the infection
and giving rise to immunological memory.
AIMS
The projects aims were to:
develop novel vaccine technologies. Early clinical
trials indicated that antigen-pulsed DCs have great
potential for treating cancer. In situ DC targeting
was developed for use as vaccines in infectious
diseases and cancer;
create tools and methodologies for the development
of DC vaccine technology, including construction
of viral and bacterial vectors, modification of RNA,
peptides and proteins, and antibody development
for targeting of the DC receptor repertoire. A
comparison was undertaken for peptides, proteins,
RNA, DNA and antigen modifications that allow
presentation via MHC molecules;
define optimal reagents and protocols for
maturation and activation of mouse and
human DC in vitro for use in vaccination. The
optimisation of protocols for both species was
compared in order to facilitate information from
preclinical models being transferred to clinical
trials for future projects. The aim was to obtain
a clear understanding of how DCs induce proinflammatory versus anti-inflammatory cytokines,
chemokines and their receptors, and how they
activate CD4+ and CD8+ T cells. It was essential
that such activation signals were tested for their
36
ability to process and present antigen to T cells,

leading to a protective Th1 response.

The project developed new adjuvants, targeting molecules
and methodologies for enhancing anti-tumour therapies and
interventions, plus vaccinations for infectious diseases
Anne OGarra
National Institute for Medical Research

London, England,
UK
Tel: +44-2 08 81 62 508
Partners:
Leonardo Biondi
Biopolo Scrl - c/o IFOM
Milan, Italy
Vicenzo Cerundolo
University of Oxford
Oxford, England
UK
Carl Figdor
University Medical Center Nijmegen

Nijmegen, Netherlands
Muriel Moser
Universit Libre de Bruxelles
Gosseliers, Belgium
Paola Ricciardi Castagnoli
University of Milano-Bicocca
Milan, Italy
Gerold Schuler
University Hospital of Erlangen
Erlangen, Germany
Anna Ranghetti
SEKMED S.R.L.
Milan, Italy
Catherine De Greef
Brucells SA
Brussels, Belgium
37
THERAVAC
Acronym: THERAVAC
Optimised delivery system

for vaccines targeted
to dendritic cells

Duration: 54 months
Type: STREP
Starting date: 1 March 2004
BACKGROUND
Novel immunotherapies are urgently required for

cancer and chronic infections as well as for prophylactic
vaccination. In response to this need, optimised delivery
systems for vaccines targeting dendritic cells are being
developed and clinically evaluated in this project. Its
approach relies on two new antigen delivery vectors:
the detoxified adenylate cyclase toxoid (ACT), and
the porcine parvovirus-like particles (PPV-VLP). They
have been shown to target dendritic cells efficiently and
specifically, allowing for a highly effective presentation
of delivered antigens to T cells. These vaccine vectors
enable the induction of strong, specific and protective
immune responses.
The expected results of the project include:
AIMS
The projects aims are as follows:
production of a GMP batch of ACT carrying the
melanoma tyrosinase epitope suitable for a phase
1/2 clinical trial;
the detailed toxicology assessment of this GMP
batch of ACT;
a phase 1/2 clinical trial in melanoma patients of
this GMP batch of ACT carrying the tyrosinase
melanoma CD8+ T cell epitope;
the understanding of the interaction of ACT with
dendritic cells at molecular and atomic details;
the detailed understanding of the mechanism of
PPV-VLP specificity and efficacy;
the engineering of improved vaccine delivery
molecules based on the improved understanding of
their functional mechanism.
38
discovery of a novel mechanism of calcium

mobilisation into myeloid cells by ACT which was
shown to be linked to AC domain translocation
across cytoplasmic membrane of cells;
important progress in understanding the
mechanisms underlying ACT interaction with
CD11b, signalling activity on myeloid cells and the
capacity to deliver the AC domain with antigens into
cells. This was efficiently used to manipulate the
antigen delivery potency of toxoid forms of ACT;
significant development made in the understanding
of how PPV-VLPs interact with dendritic
cells. Importantly, these VLPs were shown to
possess a strong adjuvant activity. The project
has demonstrated that the baculovirus (BV) is
responsible for this adjuvant effect and that it
plays a major role in the strong immunogenicity
of PPV-VLPs produced in the baculovirus-insect
cell expression system. This adjuvant behaviour
of BVs is mediated primarily by IFN/, although
mechanisms independent of type I interferon
signalling are also involved.
Claude Leclerc
Institut Pasteur
25 Rue du Dr Roux
Paris, France
Tel: +33-1 45 68 86 18
Partners:
Anita Lewit-Bentley
CNRS
Cachan, France
Rino Rappuoli
Novartis
Sienna, Italy
Paloma Rueda
INGENASA
Madrid, Spain
Peter Sebo
Institute of Microbiology
Daniel Ladant
Institut Pasteur
Paris, France
Benot Van den Eynde
ICP
Brussels, Belgium
Dorothy Xing
NIBSC
Enfield, England
UK
39
AIDS-CoVAC
Acronym: AIDS-CoVAC
Generation of a
Coronavirus-Based
Multigene AIDS Vaccine
and Evaluation in a
Preclinical SIV Model

EC contribution: 958 000
Duration: 24 months
Type: STREP
Project website: www.lfa-sg.ch
BACKGROUND
HIV infection represents one of the major health threats

in the developing world, with millions of infected people
suffering from immunosuppression-associated diseases,
such as opportunistic infections or infection-associated
cancer. Treatment with multiple highly-efficient anti-HIV
drugs is affordable in more industrialised countries only.
However, less developed countries, mainly in Africa,
require a cost-effective vaccination strategy to prevent the
further spread of the infection.
The following results are anticipated:
Coronaviruses spread via mucosal surfaces and can infect

dendritic cells (DCs). These features and their exceptional
transcription strategy make them extremely promising
candidate vaccine vectors for overcoming known
problems of current HIV vaccine approaches. This project
is pursuing research in the murine coronavirus system,
and seeks to further promote this specific line of research
in Europe in order to pave the way for the generation of
coronavirus-based HIV vaccines in humans.
AIMS
to develop a coronavirus-based multigene vaccine
that specifically targets DCs;
to evaluate the novel approach through preclinical
testing in a simian model;
to expand the understanding of the molecular
biology of coronavirus and DC interaction, and
exploit this knowledge to improve the novel virus
vector system.
40
new devices and modalities for DNA delivery to the

epidermis;
a generation of improved DNA-based vaccines
combining the advantages of GTU vectors for
long-term expression and plasmo-VLP (virus-like
particle) vectors for the presentation of antigens
onto VLPs;
generation of new proprietary HIV antigens based
on the EPIVAC optimised vector.
Burkhard Ludewig
Kantonsspital St Gallen
St Gallen, Switzerland
Partners:
Seighart Sopper
Deutsches Primatenzentrum GmbH
Gttingen, Germany
Maria Foti
Universit degli Studi di Milano-Bicocca
Milan, Italy
41
HIVAB
Generation of Broadly
Cross-Neutralising
Antibodies for Innovative
Active-Passive
HIV Vaccination Strategies
Based on Modified Ig-Gene
Transgenic Mice

Duration: 24 months
Type: STREP
BACKGROUND
Neutralising antibodies could contribute significantly to

antiretroviral treatment and vaccines so as to improve
protection from HIV infection acquired during birth or
through accidental exposure to the virus. Only a few antibodies with broad cross-clade neutralising properties are
available in the field of HIV applied research: b12, 2G12,
2F5 and 4E10. They recognise either epitopes presented
only transiently during infection of cells, or epitopes not
recognisable by unmodified immunoglobulins (2G12).
The project anticipates the following results:
While strong interest has emerged in the development

of immunogens or immunisation technologies capable of
eliciting 2F5-like Abs by immunisation, the neutralising
activity of 2F5 has not been recapitulated by administering
either gp41, gp160, or a variety of immunogens including
the 2F5 core epitope in different contexts. The importance
of residues flanking the recognition sequence in binding
2F5 has been revealed, which could explain the inability
of some, but not all, of the immunogens tested to induce
neutralising Abs.
AIMS
The projects aims were as follows:
to develop transgenic mice with distinct genetic
alterations;
to develop antigens based on synthetic HIV
envelope genes;
to identify and later produce novel neutralising
antibodies following humanisation.
This project used two experimental strategies, separately
and in combination: the first was used to produce mice
with germ line-modified immunoglobulin genes, which
introduce extended mobility into the immunoglobulin protein
backbone; the second used HIV receptor-transgenic mice
for immunisation, to favour receptor mediated transitory
stages of the viral envelope.
42
Acronym: HIVAB
better control of HIV infection in humans;

transfer of results into biotechnological applications;
recognition of immunogens from various sources (to
date, steric constraints have hindered recognition).
Hans Wolf
University of Regensburg
Regensburg, Germany
Partners:
Ralf Wagner
Regensburg, Germany
Thomas Hehlgans
Regensburg, Germany
Simon Jeffs
Imperial College of Science,
Technology and Medicine (ICSTM)
London, England
UK
Renate Kunert
Institute for Applied Microbiology
(IAM/BOKU))
Vienna, Austria
Frank Notka
Geneart GmbH
Regensburg, Germany
Hermann Katinger
Polymun Scientific GmbH
Vienna, Austria
43
INNOVAC
Acronym: INNOVAC
Highly Innovative
Strategies for Vaccination
to Poverty-Related
Diseases

Duration: 36 months
Type: SME-STREP
Starting date: January 2004
Project website: www.rhul.ac.uk/Biological-
Sciences/AcademicStaff/Cutting/
cutting.html
BACKGROUND
Between one and two million people die of malaria and

more than 300 million are infected with it every year,
mainly in Sub-Saharan Africa. Strategies for developing
malaria vaccines have been targeted at specific points in
the parasite life cycle during which the organism appears
particularly susceptible to the hosts immune system.
Preventing infection is now especially important because
resistance to anti-malarial drugs is growing.
The project seeks to achieve the validation of one or

possibly more of the platform technologies in development.
Encouraging results from one or more vaccine candidates
against either malaria or TB could lead to preclinical
studies and long-term, clinical studies in collaboration with
industrial partners.
Tuberculosis (TB) poses a similar threat to malaria in its

ability to cause devastation. This disease, thought almost
extinct only a decade ago, is now making a resurgence,
partly fuelled by the mycobacteriums growing resistance
to drug therapy. Over one third of the worlds population
has been exposed to the TB bacterium and new infections
occur every second throughout the world. One in 10
people carrying the virus will develop the full symptoms.
AIMS
The projects aim was to develop three platform
technologies that were used for developing innovative
methods of vaccination against tuberculosis (TB) and
malaria. The research platforms included:
bacterial spores robust and heat-stable
bioparticles with proven efficacy as mucosal
vaccines;
intracellular and invasive bacteria including E. coli
strains and Mycobacterium bovis (rBCG);
S-layer protein conjugates and S-layer protein
coated liposomes.
The project tested and evaluated vaccination strategies
using recombinant systems, some in their infancy and
others at a more advanced stage of development. This
included construction of vaccine vehicles, their evaluation
in animal models, challenge experiments and safety tests,
where appropriate, in order to bring potential vaccines to
the clinical evaluation stage.
44
Simon M Cutting
Royal Holloway University of London

Egham, England
UK
Tel: +44-0 17 84 44 37 60
Partners:
Rocky Cranenburgh
Cobra Biomanufacturing
Keele, England
UK
Alexander Matis
Nano S Biotechnologie
Vienna, Austria
Riccardo Manganelli
University of Padova,
Padova, Italy
Giovanni Delogu
Universita Cattolica del Sacro Cuore
Rome, Italy
Volker Heussler
Bernhard Nocht Institute for Tropical Medicine
Hamburg, Germany
Nguyen Thu Van
Vabiotech
Hanoi, Vietnam
45
ImmunoGrid
Acronym: ImmunoGrid
The European
Virtual Human Immune
System Project
Project number: IST-2004-028069

Duration: 36 months
Type: STREP
Starting date: 1 February 2006
Project website: www.immunogrid.org/
BACKGROUND
AIMS
The human immune system is composed of a complex

system of specialised cells and organs that work together
to find and kill invaders. It is responsible for distinguishing
the foreign proteins of invading pathogens and for
protecting against alien substances and infections. It can
reject transplanted organs, but it is also susceptible to
attack itself, from HIV in particular.
Leading European experts in computational immunology

are developing a virtual immune system known as the
ImmunoGrid to model the human immune system. The
ImmunoGrid project is developing separate simulators for
different pathological conditions. At present, the simulator
works mainly at cellular level, but the partners are
developing it to simulate whole organs. The complexity of
the immune system, and the fact that the most successful
pathogens each have their own unique way of overcoming
defences, means that a single simulator cannot be
developed for the whole immune system.
Computer simulation will help understand the host
immune response to attacks by pathogenic bacteria and
viruses. It will also enable researchers to assist in the
treatment of cancers of the immune system, such as
leukaemias and lymphomas.
The ImmunoGrid applications will provide tools for
clinicians and vaccine/immunotherapy developers, for
identification of optimal immunisation protocols. The
unique component of the project is that it aims to connect
molecular level interactions (which regulate immune
responses) with system level models (which study
behaviour of the immune system as a whole) a novel
approach to disease prevention and treatment.
46
to construct a database of information regarding all

aspects of the immune system;
to develop new techniques for modelling critical
intermolecular interactions in the immune system;
to test different regimes for vaccine administration
in the treatment of mammary tumours in mice.

The project anticipates the development of a virtual immune
system to aid drug development for cancer and HIV.
Elda Rossi
CINECA
Bologna, Italy
Tel: +39-0 51 61 71 515
Partners:
Vladimir Brusic
University of Queensland
Queensland, Australia
Filippo Castiglione;
Massimo Bernaschi
Rome, Italy
Santo Motta;
Francesco Pappalardo
Universita di Catania
Catania, Italy
PierLuigi Lollini
Alma Mater Studiorum Universita di Bologna
Bologna, Italy
Sren Brunak
Denmark Technical University
Lyngby, Denmark
Marie-Paule Lefranc
Montpellier, France
David Moss; Adrian Sheperd
Birkbeck College
London, England
UK
47
VaccTIP
Acronym: VaccTIP
Vaccine Strategies
for Combined Targeting
of Innate and Adaptive
Immune Pathways

Duration: 24 months
Type: STREP
Starting date: 1 May 2005
Project website: www.mtc.ki.se/groups/liljestrom/
VaccTIP/index.html
BACKGROUND
Most candidate vaccines for HIV-1 are designed to

stimulate cell-mediated immune responses, but results
show that these responses are unlikely to be sufficient
for protection. Current HIV-specific candidate vaccines
are mainly aimed at targeting cellular immunity and have
a limited immunogenicity restricted to a few epitopes.
Therefore, new vaccines that stimulate stronger and
broader T cell responses, as well as neutralising antibodies
need to be developed. Recent advances emphasised the
key role of innate immunity pathways in the stimulation of
effective adaptive immune responses. VaccTIP assessed
different approaches that activated the innate immune
system in order to selectively trigger, enhance and shape
cellular and humoral neutralising responses.
VaccTIP anticipated the development of an effective HIV

vaccine which requires the generation of both humoral
(neutralising antibodies) and cellular immunity. Specific
clinical candidates were not developed in the framework
of the consortium, however, significant steps were made
towards achieving the overall objectives even after the
end-date of the project.
AIMS
The project aimed to:
produce polymeric CD40L (Mega-CD40L) and
bacterial Flagellin as two novel adjuvants targeting
the innate and adaptive immune pathways;
construct novel alphavirus-based vaccine vectors
which stimulate innate immunity and further elevate
humoral and cellular immune responses, and to
bring technology forward in view of future implementation as global vaccines in developing countries;
analyse innate immune reactions both in human
and murine settings;
evaluate the effect on T and B cell responses to
specific antigens in human and murine models;
evaluate the adjuvanticity on recombinant alphaand poxvirus vectors expressing HIV-1 antigens.
48
Peter Liljestrom
Stockholm, Sweden
Tel: +46-8 45 72 550
Partners:
Giuseppe Pantaleo
University of Lausanne
Lausanne, Switzerland
Stphane Demotz
Apoxis SA
Jean-Claude Sirard
Institut de Biologie
INSERM BP447
Lille, France
Mariano Esteban
Centro Nacional de Biotechnologia
Madrid, Spain
49
MVACTOR
Acronym: MVACTOR
Host Immune
Activation-Optimised
Vaccinia Virus Vectors
for Vaccine Development

Duration: 24 months
Type: STREP
Project website: www.pei.de
BACKGROUND
Poxviruses engineered to express foreign genes are
recognised as potent delivery systems for heterologous
antigens and as candidate vaccines against a wide spectrum of human and animal diseases. One of these vectors,
the safety-tested highly attenuated modified vaccinia virus
Ankara (MVA) (a product of European vaccine research),
serves worldwide as the vaccinia virus strain of choice
for clinical investigations in experimental vaccination
against AIDS, tuberculosis, malaria or tumour diseases.
At present the MVACTOR consortium represents the
only European research network with prime expertise in
poxvirus research. Recent work by the project partners
significantly increased the knowledge based on versatile
poxvirus gene functions, so as to regulate virus-host
interactions and to modulate innate and adaptive host cell
immune responses.
With this project, MVA will serve as the basis to develop
a new generation of potent viral vector vaccines with
optimised host immune activating properties. Specifically,
the projects focus is to identify and/or inactivate MVA
gene functions that have immune inhibitory potential (e.g.
counteracting interferons, interleukins, CC chemokine
functions) and potentiate vector vaccine performance by
virion modification and host cytokine co-expression.
AIMS
The project aims on the development of new generation
potent viral vector vaccines with optimised host immuneactivating properties based on the highly attenuated
modified vaccinia virus Ankara (MVA). Specifically, it will
identify and characterise MVA gene functions that have
unknown and/or potentially specific immune inhibitory
capacity. Basing on these results, it will then potentiate
vector vaccine performance by rational genetic engineering
of the MVA vector through:
precise inactivation of viral immune evasion genes;
specific activation of host innate immune
responses;
50
potent presentation of target antigens by APCs;

selective expression of host adjuvant genes.

The project will derive state-of-the-art, second generation,
safe and optimised MVA vectors with superior immunogenicity and enhanced protective capacity for use in future clinical evaluation of new candidate vaccines against
infectious and tumor diseases.
Gerd Sutter
Paul-Ehrlich-Institut
Langen, Germany
Partners:
Geoffrey L Smith
Imperial College of Science,
Technology and Medicine
London, United Kingdom
Mariano Esteban
Consejo Superior de Investigaciones Cientficas
Madrid, Spain
Rafael Blasco
Institute Nacional de Investigacin y Tecnologia
Madrid, Spain
51
Diseases Specific
Vaccine Research
Introduction
Budget Total = 136,029,199
Non-infectious Diseases (19,836,426)
DISEASE SPECIFIC
VACCINE RESEARCH
Funding of translational research has been a priority for the

EC in the course of FP6, and the bulk of vaccine research
activities has been projects that are tightly associated with
a single disease or pathogen. During the 4 years of FP6,
a total of 42 disease specific collaborative projects were
Budget Total = 136,029,199

Non-infectious Diseases (19,836,426)
Poverty Related Diseases (62,659,731)
Neglected Infectious Diseases (15,006,020)
Emerging Epidemics (38,527,022)
POVERTY-RELATED DISEASES (HIV/

AIDS, MALARIA AND TB)
The three major communicable diseases (HIV/AIDS,
malaria and tuberculosis) account for nearly 18% of
the disease burden in the poorest countries and for
over 6 million deaths per year worldwide. Vaccines and
treatments to combat these poverty-related diseases
(PRD) have been slow to emerge for several reasons,
including the huge scientific challenges involved. The
combat against PRD is an established priority within the
European Commission1, and a major component of FP6
1
Poverty Related Diseases (62,659,731)

Neglected Infectious Diseases (15,006,020)
Emerging Epidemics (38,527,022)
funded with a total budget of EUR 136 million. The projects

involved more than 300 research groups from all over
Europe, as well as many non-European countries. The
projects covered diseases that can broadly be classified
into four different groups.
Number of Projects Total = 42

Non-infectious Diseases (5)
Poverty Related Diseases (17)
Neglected Infectious Diseases (8)
Emerging Epidemics (12)
was been earmarked to vaccine research in this area.

Vaccine research has been supported for all three PRDs,
but more than half of all projects were focused on HIV/
AIDS, thereby indicating the huge challenges for vaccine
research in this particular area. For each of the 3 diseases,
a major integrated project has received EC funding
of more than EUR 10 million during a 5 year period to
assemble a critical mass of diverse scientific excellence to
undertake major translational research activities. The AVIP
consortium comprises 20 research groups from Europe
and Africa with an aim to generate novel AIDS vaccine
candidates, based on combinations of HIV regulatory (Tat
COM(2005) 179 of 27.04.2005 FROM THE COMMISSION TO THE COUNCIL AND THE EUROPEAN PARLIAMENT: A European Programme for Action to
Confront HIV/AIDS, Malaria and Tuberculosis through External Action (2007-2011)
53
and/or Rev, and/or Nef) and structural (Env and/or Gag/

Pol) proteins. The largest EC-funded project to identify and
develop malaria vaccines is EMVDA. EMVDA works with
SMEs, European malaria vaccine research centres, the
European Malaria Vaccine Initiative (EMVI) and the African
Malaria Network (AMANET) to select the best malaria
vaccine candidates among a portfolio of new engineered
and improved synthetic antigens. The main EC funding to
TB vaccine development in FP6 was channeled through
the TB-VAC consortium. TB-VAC joined 33 European
institutions from 9 European and 4 African countries, and
also included a major vaccine manufacturer. The project
covers pre-clinical and early clinical development of both
subunit and new, improved BCG vaccines.
EMERGING EPIDEMICS
Influenza pandemics such as the Spanish flu of 1918 to
1919, which killed between 50 and 100 million people
around the world, is a reminder that new viral diseases
can suddenly appear or re-appear with short notice
and dramatic consequences for global public health.
A newer example stems from spring 2003, when a
hitherto unknown infectious disease, SARS (Severe
Acute Respiratory Syndrome), was reported in China,
and quickly spread to Hong Kong, Taiwan, Singapore,
Vietnam and Canada before it was contained. The EC
has acknowledged the importance of vaccine research
in emerging infectious diseases by supporting a number
of activities in this area. The largest number of projects
is focused on pandemic influenza, thereby reflecting the
current shortcomings of available flu vaccines. The main
challenge is that flu virus changes so rapidly that vaccines
formulated against one strain may be ineffective the
following year. The largest EC project to address this is
FluVacc, which is developing an improved technology for
quickly producing new live attenuated influenza vaccines
based on reverse genetics.
The other large integrated project in emerging epidemics
is Hepacivac, which aims to develop prophylactic and
therapeutic vaccine candidates that can elicit a strong
and specific T cell response against the hepatitis C virus.
54
There are around 170 million chronic hepatitis C virus

carriers about 3% of the worlds population. Around 25
000 people are infected every year, mostly young adults
who contract the virus through either intravenous drug use
or sexual contact. No vaccine has yet been developed and
the available antiviral therapy only works in a few patients.
Hepacivac is focusing on the development of two Hepatitis
C vaccine candidates. The first uses gene-based encodes
for the 2000 amino acid-long HCV Non Structural region
(from NS3 to NS5B) and using adenoviral vectors for
delivery. The second consists of the recombinant HCV
glycoproteins gpE1 and gpE2 associated to resemble a
pre-virion envelope structure.
Besides influenza and hepatitis C, vaccine research for possible vaccines against SARS has also been funded by the
EC as part of vaccine research for emerging epidemics.
NEGLECTED INFECTIOUS DISEASES

Neglected infectious diseases (NIDs) receive little attention
from the media and public in comparison with high
profile diseases such as HIV/AIDS, malaria and TB, but
their effect can be just as devastating. NIDs are a highly
diverse group of infectious diseases, including protozoal,
bacterial, viral and helminth infections. They include some
of the most common chronic infections among the worlds
poorest people, and they are responsible for millions of
disabilities and deaths every year.
The EC has been supporting vaccine research in neglected
infectious diseases during successive framework
programmes since the early 1980s. Under FP6, it has
funded a number of projects that are addressing such
diverse topics as vaccines against diarrhoeal diseases
caused by rotavirus (HEVAR), lyme disease (BOVAC)
and potential vaccine approaches for helminth infections
(TRANCHI). The EC funded vaccine projects for neglected
infectious diseases are mostly STREP projects with an
EC contribution between EUR 1 million and EUR 2 million
for a project period of two years or less. However, as they
are addressing infectious diseases that are otherwise
neglected, many of the projects are expected to have an
impact in terms of societal value that supersedes their

financial magnitude.
NON-INFECTIOUS DISEASES
The possibility of creating vaccines for a host of noninfectious diseases such as cancer, neurodegenerative
diseases and autoimmune diseases provides one of the
most exciting fields for current vaccine research. It holds
the potential to meet a huge unmet medical need for
some diseases, while for other diseases it may provide
a future alternative to traditional treatments that often are
costly, only partially effective and sometimes associated
with several adverse effects. With the exception of a
vaccine project against Alzheimers disease (MIMOVAX),
EC efforts in this area have been concentrated on cancer
vaccines. The projects address identification of specific
tumour antigens that are present in cancer cells, such
as in leukaemia, and thereby provide potential immune
targets for which immunogenic vaccines may possibly be
designed. Other projects are targeting some of the major
cancer types, such as melanoma, carcinoma, and lung
cancer. This includes the CANCERIMMUNOTHERAPY
consortium, which comprises 22 partners that have
received a total EC contribution of EUR 12 million to
develop a safe and efficient therapeutic vaccine against
cancers such as melanoma. This will initially be done by
comparing the effect of various types of vaccines, such as
peptides and RNA with different types of immunological
adjuvants and DCs. The field of vaccines for non-infectious
diseases is highly promising, but it should be kept in mind
that there are still many roadblocks to be overcome. Some
of the basic discoveries and necessary technologies may
not yet be sufficiently matured. As such, some of the EC
funded activities in basic vaccinology will undoubtedly
also benefit the future advancement of vaccines for noninfectious diseases.
55
AVIP
Acronym: AVIP
AIDS Vaccine
Integrated Project

Duration: 72 months
Type: IP
Project website: www.avip-eu.org/
BACKGROUND
Vaccines based on viral structural products (Env/Gag/
Pol) alone have failed to prevent infection by Human
Immunodeficiency Virus (HIV)/Simian Immunodeficiency
Virus (SIV). New strategies have recently been developed
aimed at blocking virus replication and onset of HIV/SIV
in the absence of sterilising immunity. Control of virus
replication may modify the virus-host interaction, favoring
the host immune response, providing protection from
disease progression and reducing virus transmission
to healthy individuals. This strategy, useful for both
preventive and therapeutic interventions, should include
both nonstructural and structural viral products, since
vaccines targeting viral structural products (Env/Gag/Pol),
as well as viral regulatory gene products (Tat/Rev/Nef),
should be superior at inducing immune responses to both
early and late viral products.
AIMS
The aims of the project are:
to generate novel HIV-1 vaccine candidates to be
tested in phase I preventive and therapeutic trials in
Europe within the five-year programme. To achieve
this goal, four novel vaccines have been selected
from a larger pool based on two criteria: the
combination of HIV regulatory (Tat and/or Rev, and/
or Nef) with structural (Env and/or Gag/Pol) genes/
products, and the advanced stage of development
of single components, including efficacy studies in
monkeys and new murine efficacy models;
to conduct parallel preventive and therapeutic
phase I trials in Europe with the four novel
combined vaccines;
to perform feasibility studies and technology
transfer in Developing Countries (DCs) for phase II/
III trials;
to carry out training in EU and in DCs through the
AVIP International School;
to ensure community involvement both in EU and
DCs.
56
PRD-AIDS

Development of vaccines based on the combination
of regulatory and structural genes.
Demonstration of the safety of the immunogenicity
of the vaccine candidates through preclinical
studies (mice and monkeys). For some of them
(TatV2Env and HIV-1 multigene approach)
the protective efficacy was also successfully
demonstrated in preclinical efficacy animal models
(mice and monkeys).
Clinical trials (preventative or therapeutic) for some
vaccine candidates (HIV Tat clade B, HIV V2 Env
clade B, MVA-HIV Nef clade B, multi-HIV antigens/
epitopes clade B, HIV multigene clade B) have
been already performed or started in the past year.
New phase I and II clinical trials (Multi-HIV antigens/
epitopes multiclade vaccine; HIV multigene clade A,
B, C vaccine; Tat clade B combined with HIV V2
Env clade C vaccine) are expected to start during
the year 2008. Recently, two new partners joined
AVIP Consortium, the Ndlela vaccine site (p18)
in South Africa and the NRL-Mbabane vaccine
site (P19) in Swaziland. Cooperation with DCs for
building up the capacity of potential vaccine clinical
sites and upgrading local infrastructure is in place.
Standardisation of techniques and procedures are
ensuring reproducibility of all results.
Training in all AVIP activities, both in the EU and
in DCs is ongoing. The main instrument for the
training activity is the AVIP International School,
which has been created by joining existing centres
in the EU and South Africa. Many of the assays
and other aspects of the phase I trials will be used
in future phase II and III trials in South Africa and
Swaziland and the participation of South African
and Swazi researchers will promote continuity in the
development of the vaccines.
Exploitation of synergies with national and
international ongoing programmes, such as the
Italian Concerted Action on HIV/AIDS Vaccine
development (ICAV) and the Swedish International
Development Cooperation Agency (SAREC/
SIDA). The project also has bilateral programmes

with Europe and DC, such as the HIV Incidence
Study (HIVIS-INCO-FP6), the Very Innovative
AIDS Vaccine (VIAV-STREP-FP6), the Mucosal
Vaccine Approaches for Poverty Related Diseases
(MUVAPRED-IP-FP6), the European Vaccines and
Microbicides Enterprise (EUROPRISE-NoE-FP6),
the Standardization of HIV Neutralization Assays
to be Used in Vaccine Research and Clinical Trials
(NEUNET-SSA-FP6).
Mauro Magnani
University of Urbino
Urbino, Italy
Ioana Stanescu
FIT Biotech Oyj Plc
Tampere, Finland
Volker Erfle
Helmholtz Center Munich
Neuherberg, Germany
Rino Rappuoli / Susan Barnett
Novartis Vaccines and Diagnostics Srl
Siena, Italy
Dr Barbara Ensoli
Director National AIDS Center

Viale Regina Elena 299 C.A.P. 00161
Rome, Italy
Tel: +39-0 64 99 03 209
Partners:
Britta Wahren
Microbiology and Tumorbiology Center, Karolinska Institute
Stockholm, Sweden
Frances Gotch
Imperial College, Chelsea and Westminster Hospital
London, England
UK
Eftyhia Vardas
Perinatal HIV Research Unit of the Wits Health Consortium
Sowetho, South Africa
Richard Glashoff
University of Stellenbosch Medical School
Tygerberg, South Africa
Roger Le Grand
SNV/DRM/SDV/CEA Laboratoire dImmuno-Pathologie
Experimentale (LIPE)
Fontenay-Aux-Roses, France
Riccardo Gavioli
University of Ferrara
Ferrara, Italy
Carlos A Guzman
Helmholtz-Zentrum fr Infektionsforschung GmbH
PRD-AIDS
57
RMVHIV
Acronym: RMVHIV
Recombinant Measles
Virus as a Vector
for HIV Vaccines

Duration: 49 months
Type: IP
BACKGROUND
This project aims at demonstrating the safety and
immunogenicity of a novel recombinant measles virus
(MV) vector for use as an AIDS vaccine. The vector is
replication competent in vivo and is derived from a widely
used measles vaccine strain (Schwarz), which is known
to induce very long-lasting immunity. This novel vector
potentially offers a unique combination of safety and
potency. The recombinant HIV MV vectors will express
three relatively conserved HIV proteins (i.e. Gag, Pol, Nef)
from HIV clade B and A strains. A Good Manufacturing
Practices (GMP) compatible production process for the
recombinant MV vector will be developed and a GMP lot
will be produced for two clinical studies.
The first study will evaluate the safety profile of the
MV vector, while the second study will also assess the
immunogenicity in MV-immune volunteers. With these
two clinical studies, the project will specifically address
potential shedding of the recombinant vector into the
environment and the potential negative impact of preexisting MV immunity.
The measles vaccine, a live attenuated strain of MV, is
one of the safest human vaccines available and has been
given to billions of children since the 1960s. However,
because of the inadequate distribution of the vaccine in
developing countries, there are still 45 million cases of
measles and 800 000 child deaths per year worldwide.
The Pasteur Institute has developed an MV vector based
on the Schwarz strain, the safest and most widely used
vaccine strain. The consortium is proposing to construct
recombinant MV vectors that express the HIV-1 clade B
and A Gag, Pol, and Nef proteins. These proteins possess
highly conserved regions that have been shown to be
the target of CD8-positive cells, and thereby constitute a
promising antigenic composition for an HIV vaccine. It has
been demonstrated that CD8-positive cells from individuals
infected with virus strains from different clades are highly
cross-reactive with respect to the Gag, Pol, and Nef
proteins. By assuming a similar cross-reactivity for vaccine-
58
PRD-AIDS
induced immune responses, RMVHIV is based initially on

HIV clade B antigens. The choice of clade B antigens will
also allow for subsequent combination vaccine regimen
using GSKs clade B adjuvanted protein vaccine.
AIMS
The objective of RMVHIV is the demonstration of safety
and immunogenicity of a recombinant HIV MV vector
in adult HIV-uninfected volunteers. This includes the
identification of a suitable dose of recombinant MV, the
demonstration of an acceptable reactogenicity profile,
and the characterisation of potential virus shedding.
Furthermore, the vaccine will have to induce significant
levels of HIV-specific CD8-positive cells in volunteers with
pre-existing immunity, and ideally also measurable CD4positive cell and antibody responses.

The project has defined a mostly sequential development
path. The first stage is the construction and characterisation
of recombinant MV expressing HIV clade B Gag, Pol,
and Nef proteins. The characterisation includes the
evaluation of immunogenicity in mice, established growth
characteristics in a production cell line and analysis of
genetic stability. Based on these results, a corresponding
HIV clade A MV vector will be developed and compared to
the clade B vector in a monkey immunogenicity study.
The consortium will assess several parameters that are
relevant for the development of a production process that
is compatible with GMP manufacture. When a suitable
HIV clade B MV vector is selected and a process has been
established, a GMP clinical lot production will be initiated
and the resulting material subjected to a formal QC release.
The GMP material will also serve for toxicology studies in
macaques in order to assess the reactogenicity, toxicity,
biodistribution and shedding of the recombinant MV. The
analysis of the GMP lots, the data from the toxicology
study, and other supportive data will be compiled in a
dossier for submission to regulatory authorities.
Gerald Voss
Gerald Voss
GlaxoSmithKline Biologicals
Rixensart, Belgium
Tel: +32-2 65 68 243
Partners:
Frdric Tangy
Institut Pasteur
Paris, France
Geert Leroux-Roels
Gent Universiteit
Ghent, Belgium
Odile Launay
Centre Cochin-Pasteur dEssais Vaccinaux,
Hpital Cochin
Paris, France
David Lewis
St Georges, University of London
London, England
UK
Neil Almond
National Biological Standards Board
Potters Bar, England
UK
PRD-AIDS
59
AUTO/ALLO CELL-HIV
Development of a Novel
Therapeutic HIV-1 Vaccine:
Horizontal Gene Transfer
by Using Apoptotic
HIV-1 DNA Containing
Activated T Cells
Acronym: AUTO/ALLO CELL-HIV

Duration: 36 months
Type: STREP
Project website: www.avaris.se/
BACKGROUND
HIV/AIDS has now killed more than 20 million people

worldwide and over 40 million are living with the virus. It is
continuing to spread and its worse casualties are in Africa
where 2 million people are dying of it every year and 11
000 contract it every day. Progress has been made on
HIV/AIDS research, but a suitable vaccine has not yet
been found. Novel therapies and a successful prophylactic
vaccine are urgently needed.
The study expects to obtain safety measurements and

proof of concept in macaques. In addition, GMP compliant
production protocols will be developed. If feasibility and
efficacy in a therapeutic HIV trial can be shown, it will open
up the possibility of applying the concept to a preventive
HIV vaccine.
AIMS
The project has discovered that genes can be horizontally
transferred to neighbouring cells by the uptake of
apoptotic cells, which also allows transfer of proteins
leading to cross-presentation of antigens. The aim is to
develop a therapeutic HIV vaccine using apoptotic cells
as the antigen delivery system. In order to achieve this the
project is performing the following actions:
carrying out safety and immunogenicity studies in
macaques;
optimising the techniques for production of
AutoCell/AlloCell in a good management practice
(GMP) certified Cell Therapy Centre;
producing individualised prototype AutoCell/AlloCell
compositions;
launching a phase I/II clinical trial.
Anti-retroviral treatment leads to reconstitution of immune
responses to many pathogens, but it does so without
the emergence of HIV-specific responses. Anti-retroviral
treatment also allows patients to respond to immunisation
using recall antigens and neo-antigens. Hence, it may be
feasible to induce a novel adaptive HIV-1-specific immune
response by therapeutic vaccination, which would also
allow the patient to stop anti-retroviral medication.
60
PRD-AIDS
Anna-Lena Spetz
Stockholm, Sweden
Partners:
Gerrit Koopman
Biomedical Primate Research Center
Rijswijk, Netherlands
Eva-Maria Fenyo
Lund University
Luc Perrin
Geneva University Hospital/Geneva Medical School
Geneva, Switzerland
Jan Andersson
Karolinska University Hospital Huddinge

Stockholm, Sweden
Brigitte Autran
INSERM U543
Paris, France
PRD-AIDS
61
Pox-gene
A Combined Pox-Virus/
Lentiviral Vector System
to Treat HIV Infection;
Immunisation and Direct
In Vivo Gene Transfer
in T-Lymphocytes
Acronym: Pox-gene
Duration: 36 months
Type: STREP
Project website: www.bprc.nl
BACKGROUND
Despite its successes, it is clear that highly active

anti-retroviral therapy (HAART) cannot eradicate HIV
infection and that virus rebounds as soon as treatment
is interrupted. In addition, HIV infection in humans
induces chronic changes in the phenotype and function
of CD4 and CD8 T-cells as well as dendritic cells, which
are only partly restored after the initiation of HAART. In
order to alleviate the permanent dependency on HAART,
alternative therapies must be developed to restore normal
immune function. Attenuated pox-viruses are currently
under evaluation as prophylactic or therapeutic vaccines
against AIDS.
The expected results for this project are:
This project exploits attenuated pox-viruses to develop

a treatment that reinforces patients immune response
to HIV and simultaneously renders their T cells resistant
to infection.
AIMS
The project aims to develop a combined vaccination/
gene therapy protocol for the treatment of HIV infection.
Currently available technology for genetically modifying
MVA pox-viruses was exploited to create a vector that
expresses both HIV-1 proteins and an HIV inhibitory
lentiviral construct. Target cells infected with MVA therefore
express not only HIV-1 proteins capable of stimulating
antigen specific T cells, thereby boosting anti-HIV-1
immune responses, but will also release lentiviral particles
capable of transducing antigen stimulated T cells with an
anti-viral gene that protects them from HIV-1 infection.
62
PRD-AIDS
the development of pox-gene vectors effective for

antigen specific stimulation and transduction of T
cells;
the development of gene constructs that encode
secreted HIV inhibitory peptides.
Gerrit Koopman
Biomedical Primate Research Centre

Partners:
Dorothee von Laer

Georg-Speyer-Haus Infektions biologie
Frankfurt, Germany
Gerd Sutter
Paul Ehrlich Institut
Langen, Germany
Balbino Alarcn
Consejo Superior de Investigaciones Cientificas
Madrid, Spain
Giuseppina Li Pira
Advanced Biotechnology Centre
Genoa, Italy
Karen Willard-Gallo
Brussels, Belgium
PRD-AIDS
63
Allomicrovac
Acronym: Allomicrovac
A Combined
Microbicidal-Immunising
Strategy Against SIV
and HIV Infection

Duration: 24 months
Type: STREP
BACKGROUND
There are two known natural HIV-1 resistance states:

alloimmunity and homozygous CCR5 mutation. The
protein HSP70 is also found within the virion membrane
of HIV-1 and functions as a chaperone during intracellular
transport. HSP70 expression is significantly increased in
lymphocytes from HIV-1 infected subjects.
It is expected that in a proportion of macaques treated with

the trimolecular construct infection will be prevented at the
mucosal site of viral entry. As the construct is immunogenic,
repeated applications will induce immune responses and
memory to the vaccine components; this may prevent
subsequent viral challenge. Thus, the microbicidal agent
may also function as a preventive vaccine.
There is a striking resistance to HIV-1 infection in

homozygous 32 CCR5 mutation, found in about 1 % of
caucasians. These individuals lack cell-surface expression
of CCR5 generate a large amount of CC chemokines
(CCL-3, CCL-4 and CCL-5) and may develop antibodies
to CCR5, but they do not suffer from ill health. This project
used the principle of potentiation, where a reagent enhances
sensitisation to an antigen with regard to alloimmune,
CCR5 and HSP70 responses.
AIMS
The project aims to utilise one cohort of macaques for
three HIV-1/SIV preventive methodologies in microbicide,
preventive and therapeutic immunisation. Macaques
that are not infected are to be evaluated for preventive
immunity; infected animals are utilised for therapeutic
immunisation two months after infection.
Emphasis is on determining whether a trimolecular
construct of MHC antigens combined with microbial
HSP70 and extracellular CCR5 peptides can be utilised
in microbicidal, preventive and therapeutic immunisation.
Combining a short term microbicide with a long term
preventive vaccine will deal with the problem of repeated
applications of microbicides before sexual intercourse.
64
PRD-AIDS
By early 2008, the HSP70-CCR5 construct for immunization was produced, consisting of dextramers of macaque
MHC A1, A4 and A8 alleles and dextramers linked to
HSP70 and CCR5 N terminal and loop 1 and 2 peptides.
The final vaccine constructs was assembled in the molar
ratio of 1 mol Dextran / 10 mol MHC / 8 mol HSP70CCR5tripeptide. Two groups of macaques were treated vaginally
by the dextramers MHC-HSP70-CCR5 peptide construct
at 2-weekly intervals, followed 30min. later by 50TCID of
SIVmac251. A 3rd group of macaques was treated with
saline prior to treatment with SIVmac251 and a 4th was
a naive control group. The macaques are monitored for
innate immune factors, vaginal and serum antibodies, CC
chemokines, cytokines and T cell functions. The investigation should be completed by the end of the year, when
the results will be analysed and published.
Thomas Lehner
Guys Hospital
London, England
UK
Telephone: +44 207 188 3072
Partners:
Gunnel Biberfeld
Karolinska Institute
Solna, Sweden
Jrgen Schller,
DakoCytomation,
Glostrup, Denmark
Mahavir Singh
Lionex Diagnostics and Therapeutics
Rigmor Thorstensson
Swedish Institute
for Infectious Disease Control
Solna, Sweden
Robert Vaughan,
Guys Hospital
London, England
UK
Yufei Wang,
Guys Hospital
London, England
UK
PRD-AIDS
65
VIAV
Acronym: VIAV
Very Innovative
AIDS Vaccine

Duration: 24 months
Type: STREP
Project website: www.iss.it
BACKGROUND
There are indications that the HIV Tat protein increase HIV
cell absorption, infectivity and tropisms by interacting with
components of the HIV membrane and envelope protein
(Env). Because the interaction between Tat and Env is
believed to increase the generation of complex-specific,
neutralisation-sensitive epitopes and/or the stabilisation
of cryptic and/or transiently exposed Env epitopes, a
vaccine based on Tat-Env complexes was considered
likely to generate protective immune responses against
vulnerable viral targets.
The project identified novel HIV/AIDS vaccine immunogens

and formulations for inducing broad immunity against
HIV. Tat Env complexes were characterised and used to
immunise small animals. Neutralising antibody responses
were also characterised and novel neutralisation-sensitive
complex-induced epitopes identified.
AIMS
The intention of this project was to develop a highly innovative Tat-Env complex-based vaccine capable of inducing
cross-clade neutralising antibodies against novel, neutralisation sensitive Env epitopes to prevent HIV infection and/
or AIDS progression. This was achieved using new antigen
design as a result of novel virological, immunological and
modelling data from the VIAV consortium.
66
PRD-AIDS
Flavia Ferrantelli

Rome, Italy
Tel +39-0 64 99 03 209
Partners:
Banci Lucia
Consorzio Interuniversitario
Risonanze Magnetiche di Metalloproteine
Florence, Italy
Eva Maria Fenyo
Lunds Universitet
Lund, Sweden
Dag Helland
Universitetet i Bergen
Bergen, Norway
Elisa Gargiulo
DIATHEVA
Fano, Italy
PRD-AIDS
67
HIV VIROSOMES
Development of
a New Vaccine
against HIV:
Virosomes
Incorporating
HIV Proteins

Duration: 36 months
Type: STREP
BACKGROUND
Presently, only few broadly neutralizing antibodies against

HIV-1 are known, two of those binding to sequences
located within the membrane proximal external region
(MPER) of the HIV-1 transmembrane glycoprotein gp41
(2F5 and 4E10). Numerous efforts have been undertaken
to elicit 2F5- and 4E10-like antibodies, none has brought
a major breakthrough. There is evidence that the lipid
environment is required for full epitope recognition,
which can be achieved by the use of liposomes. The
ability of liposomal vaccines to raise humoral as well as
cellular immune responses is desirable for an effective
immunization against HIV-1. However, major drawbacks
concerning the use of liposomes have been the
cumbersome production methods with limited possibilities
to control size distribution and antigen incorporation rates,
denaturation of sensitive proteins, lack of scalability,
high costs and difficulties to comply with regulatory
requirements for human application.
To allow a fast-track development of the proposed

vaccines the following tasks were pursued during the
three project years:
AIMS
The objective of the project was to develop a preventive
HIV vaccine using a focused straight-forward approach.
The aim was to incorporate native proteins derived from
primary HIV strains into liposomes generated by a novel
large scale liposomal technology. Alternatively, recombinant
HIV proteins should be used. This project included:
a. stabilisation of the native structure and
conformation of native and recombinant HIV
envelope proteins in liposomes
b. selection of candidate vaccines in small animal
immunisation studies
c. establishment of immunogenicity, and eventually,
efficacy in the rhesus macaque model
d. establishment of a GMP compliant process suitable
for production of clinical material
68
Acronym: HIV VIROSOMES
PRD-AIDS
Generation of recombinant and primary virosomes

(containing recombinant gp41 antigen or primary
proteins)
Characterisation of virosomes
Safety testing of liposomal preparations
Small animal immunisation studies
Non-human primate studies
Establishment of medium/large scale virosome
production process
Gabriela Stiegler
Polymun Scientific Immunbiologische

Forschung GmbH
Nussdorfer Laende 11
1190 Vienna
Austria
Tel: +43-1-36006-6208
Fax: +43-1-3697615
Partners:
Biomedical Primate Research Centre (BPRC)
Department of Virology
The Netherlands
European Molecular Biology Laboratory (EMBL)
Grenoble Outstation
France
Institute of Applied Microbiology (IAM)
University of Natural Resources
and Applied Life Sciences
Austria
Polymun Scientific Immunbiologische
Forschung GmbH
Austria
PRD-AIDS
69
TIP-VAC
Acronym: TIP-VAC
Explaining and
Improving Efficacy of
Targeted Immunodeficiency
Virus-like Particle
Vaccines against AIDS

Duration: 24 months
Type: STREP
Project website: www.ruhr-uni-bochum.de
BACKGROUND
Work on live attenuated immunodeficiency viruses in

non-human primate models showed that a vaccine can
provide protection from progression to AIDS. A number
of effector mechanisms, including neutralising antibodies
and CD8+ cytotoxic T lymphocytes, are likely to contribute
to protection. A common feature of vaccination with
recombinant viral proteins and whole inactivated viruses
is injection of exogenous antigens, which predominantly
leads to MHC-II restricted cellular immune responses and
production of antibodies. Expression of antigens by cells of
the vaccinees should lead to the presentation of antigens
on MHC-I and MHC-II molecules. Therefore, DNA and
viral vector vaccines have been studied extensively and
depending on the stringency of the challenge system,
various degrees of protection have been observed. Instead
of using viral vector systems to induce MHC-I and MHCII-restricted immune responses, a heterologous surface
protein was incorporated into immunodeficiency virus-like
particles, which should increase uptake and presentation
of the exogenous viral antigens on MHC-I and MHCII molecules. This might explain evidence for protection
from disease progression in monkeys immunised with
these targeted virus-like particles.
The partners had expected to confirm vaccine efficacy in

a larger number of animals, however the VLP vaccine that
was tested did not result in a significant show of efficacy
during a short vaccination regimen.
AIMS
The aims of the project were to:
determine the efficacy of the VLPs in a larger number of
animals;
understand better the requirements for and the
mechanisms of protection;
further improve the targeted VLPs.
The project developed a targeted immunodeficiency viruslike particle vaccine (VLP), which has a heterologous
viral surface protein incorporated in the membrane of the
particle. This should increase uptake and presentation
of VLPs by dendritic cells. A pilot vaccination experiment
in the SIV/macaque model provided strong protection
against challenge with a pathogenic SIV.
70
PRD-AIDS
Furthermore, studies showed that CD8+ T cell responses

were not sufficient to control viral replication. Overall,
the project showed that VLP priming (and boosting with
adenoviral vectors) could facilitate the induction of protective
mechanisms such as the neutralizing antibody responses.
Klaus berla
Ruhr-University
Bochum, Germany
Tel: +49-2 34 32 23 189
Partners:
Paul Racz
Hamburg. Germany
Ralph Steinman
Henry G Kunkel
The Rockefeller University
New York, USA
Heribert Stoiber
Medical University Innsbruck
Innsbruck, Austria
Ralf Ignatius
Charit University Medicine Berlin
Berlin, Germany
Mariagrazia Uguccioni
Deutsches Primatenzentrum (DPZ) GmbH
Gttingen, Germany
PRD-AIDS
71
EPI-VAC
Acronym: EPI-VAC
Identification of Novel
Epitopes as HIV-1
Vaccines Candidates

Duration: 24 months
Type: STREP
Starting date: 1 August 2005
Project website: www.dbbm.unina.it
BACKGROUND
Despite the need for an effective HIV-1 vaccine, truly

prophylactic candidates are not currently available. The
current HIV-vaccine candidates tested to date, preclinically
or clinically, have all failed to protect from primary infection
and have afforded limited protection. The identification
of immunogens eliciting broadly neutralising antibodies
has hampered the efforts of researchers seeking to
develop a truly prophylactic HIV-1 vaccine. This lack of
significant cross-protection has fuelled concerns as to
whether classical Env-based vaccines can afford enough
protection against field isolates.
EPIVACs results were as follows:
AIMS
This project aimed to select epitopes that mimic
neutralisation-sensitive domains of HIV-1 envelope and
may function as candidate HIV-1 vaccines and. It carried
out the following strategies to meet its objective:
screening of random peptide libraries with novel
MAbs that neutralise primary HIV-1 isolates
assigned to distinct clades;
designing 30 to 40 amino acid peptides that mimic
discontinuous regions of gp120 and gp41 that are
sensitive to neutralisation by antibodies and are
conserved among HIV strains of distinct clades.
In order to meet the challenge, EPI-VAC developed pools
of innovative immunogens that mimic conserved regions
of the viral envelope and are shared by a substantial
percentage of primary viral isolates assigned to distinct
clades from disease progression, if volunteers are
exposed to heterologous isolates (1-3).
72
PRD-AIDS
development of novel vaccine candidates;

optimisation of vaccine delivery;
immunological evaluation of vaccine candidates in
rodents.
Giuseppe Scala
University of Naples Federico II

Naples, Italy
Tel: +39-3 40 77 60 115
Partners:
Vincenzo Pavone
University of Naples Federico II
Naples, Italy
David Davis
Foundation Biomedical
Primate Research Center
Gabriela Stiegler
Polymun Scientific
Immunbiologische Forschung GmbH HIV Research
Vienna, Austria
Boris Ferko
University of Applied Life Sciences
and Natural Resources
Institute of Applied Microbiology
Vienna, Austria
PRD-AIDS
73
EMVDA
Acronym: EMVDA
The European Malaria

Vaccine Development
Association

Duration: 60 months
Type: IP
Project website: www.emvda.org
BACKGROUND
There is considerable optimism that a malaria vaccine can
be developed. This is based on the fact that acquisition
of immunity induced by natural infection does eventually
prevent mortality and provide protection against clinical
disease. There has been interest in the development of
malaria vaccines for over 30 years, with the initial research
emphasis on attenuated or killed whole organisms,
and more recently on subunit-based approaches. The
malaria parasite is a complex organism with an elaborate
lifecycle; as a consequence much effort has been devoted
to identifying molecules that stimulate host immunity
and identifying protective components of that immune
response. In parallel, research on delivery technologies
has sought to develop ways to evoke protective immune
responses by active immunisation.
Three stages of the malaria parasite lifecycle are targeted
for vaccine development: the pre-erythrocytic, the asexual
and the sexual blood stages. This project is very largely
focused on the asexual blood stage that is responsible for
the disease. This is the area in which European laboratories
are probably most globally competitive, and it allows them to
focus relatively limited resources to the greatest advantage.
The projects strategy includes the development of new
engineered and improved synthetic antigens, for example
with amino acid sequences from two or more antigens or
with modifications to improve immunogenicity.
AIMS
The goal of the project is to systematically develop and
test malaria vaccines by comparative and continuous
evaluation of candidates. The best malaria vaccine
candidates are being selected through collaborations
with two SMEs, eight European malaria vaccine research
centres, the European Malaria Vaccine Initiative (EMVI)
and the African Malaria Network (AMANET). These
vaccines will be developed further within a process that
includes antigen validation, as well as the creation of a
vaccine development rationale and early proof-of-principle
clinical trials.
74
PRD-Malaria
To develop a vaccine for malaria a scientific and technological structure supported by effective management
has to be established in order to move candidate malaria parasite antigens through five stages of preclinical
and clinical testing. Individual candidates are at different
stages of development. Stringent go/no-go criteria are
being used to assess and compare competing antigens,
and delivery systems to focus resources on to the most
credible vaccine candidates. Emphasis and resources
are being focused on moving candidate vaccines into
clinical trials.

EMVDA anticipates the development of a vaccine to reduce
the burden of malaria.
Dr Odile Leroy
European Malaria Vaccine Initiative

c/o Statens Serum Institut
Artillerivej 5
Copenhagen
Tel: +45-3 26 8 3798/8288
Website: www.emvi.org
Partners:
Michael Theisen
Statens Serum Institut
Copenhagen, Denmark
Reinhard Glck
CSO Etna Biotech
Bern, Switzerland
Rinaldo Zurbriggen
Pevion Biotech
Bern, Switzerland
Adrian Hill
The Wellcome Trust Centre for Human Genetics
Oxford, England
UK
Anthony Holder
National Institute for Medical Research (NIMR)
London, England
UK
Roma Chilengi
African Malaria Network Trust (AMANET)
Tanzania, Africa
Gerd Pluschke
Swiss Tropical Institute
Basel, Switzerland
Klavs Berzins
The Wenner-Gren Institute, Stockholm University
Stockholm, Sweden
Franois Spertini
Centre Hospitalier Universitaire Vaudois
Peter Kremsner
Eberhard-Karls Universitt Tbingen
Tbingen, Germany
Alan Thomas
David Cavanagh
University of Edinburgh
Edinburgh, Scotland
UK
Robert Sauerwein
University Hospital Faculty of Medical Sciences
PRD-Malaria
75
PRIBOMAL
Preclinical Studies
towards an Affordable,
Safe and Efficacious
Two-Component
Paediatric Malaria
Vaccine
Acronym: PRIBOMAL
Duration: 36 months
Type: STREP
Project website: www.crucell.com
BACKGROUND
About 1 to 2 million people die of malaria every year,

mostly in sub-Saharan Africa. Predominant among the
victims are pregnant women and children. Nearly 90% of
these child malaria deaths are in children younger than 5
years. A safe, affordable paediatric malaria vaccine that
provides long lasting protection against malaria urgently
needs to be designed. This project is generating and
testing an innovative malaria vaccine consisting of a prime,
to be administered at birth, of a novel recombinant Bacille
Calmette-Gurin (BCG) vector carrying preferentially
multiple antigens derived from the Plasmodium falciparum
parasite - the cause of malaria. The priming vaccine will be
followed by a booster vaccination 14 weeks after birth.
The project will deliver an effective paediatric malaria

vaccine candidate ready for development and clinical
trials. Extensive knowledge will be gained regarding
immunological features of different vaccination schedules,
in combination with information on their protective ability.
This information will help design future malaria vaccines.
AIMS
The consortium aims to show in preclinical studies
the safety and efficacy of a novel and affordable twocomponent paediatric malaria vaccine.
76
PRD-Malaria
Jaap Goudsmit
Crucell Holland
Leiden, Netherlands
Tel: +31-0 71 52 48 755
Partners:
Stefan Kaufmann
Max Planck Institute for Infection Biology
Berlin, Germany
Marita Troye-Blomberg
Stockholm University
Stockholm, Sweden
Tom Van der Poll

University of Amsterdam
Amsterdam, Netherlands
Robert Sauerwein
Radboud University
Nijmegen Medical Centre
Henriette Skovgaard Andersen
ACE BioSciences
Odense, Denmark
Clemens Kocken
PRD-Malaria
77
SME-Malaria
Acronym: SME-Malaria
SME Led Malaria

Vaccine Initiative

Duration: 36 months
Type: STREP
Project website: www.malariastrep.eu
BACKGROUND
The attenuated MeV vaccine on which this projects

vectors are based is used worldwide, with excellent safety
and efficacy records. As the vaccine is easy to produce
economically, the vector is of great interest for the
development of multivalent vaccines for poor countries,
such as in sub-Saharan Africa. The genetics of MeV and
the technology for rescue of recombinant MeVs is well
established and the long-lasting immunogenicity induced
both in transgenic mice susceptible to MeV infection and
in macaques using several vectored transgenes up to 5
kb in length, has been documented.
SME-Malaria expects that at least one of the candidate

antigens will prove efficacious and safe following preclinical
studies; it will then be produced under GLP conditions.
The most promising P. falciparum antigen-vector combinations will be used in monkey immunisation studies (these
animals can be efficiently infected with MeV) to determine
various aspects of potential safety, as well as humoral and
cellular immunity.
This project is investigating new malaria vaccine candidates with the objective of taking at least one through to
Good Laboratory Practices (GLP) pilot scale up. The most
promising candidates will undergo in vitro and in vivo testing, lead optimisation, and safety and toxicology testing
according to GLP standards.
The two selected antigens, MSP-1 and AMA-1, are leading vaccine candidates associated with the surface of
merozoite, the parasite form that invades uninfected erythrocytes. Both were originally identified as targets of antibody-based immunity directed against asexual blood stage
parasite multiplication. It has subsequently become clear
that both antigens are also expressed during the development of liver stage schizonts (the prelude to blood stage
development). They represent potential targets for cellular
immunity-based mechanisms of immunity and protection.
AIMS
The project aims to obtain at least one malaria vaccine
candidate stably expressed in MeV that induces humoral
and cellular immune responses.
78
PRD-Malaria
Reinhard Glck
Etna Biotech SpA

Catania, Italy
Tel: +41-3 19 80 65 00
Partners
Hermann Bujard
University of Heidelberg
Heidelberg, Germany
David Arnot
Edinburgh University
Edinburgh, Scotland
UK
Yves Barbier
Texcell
Evry, France
Alan Thomas
PRD-Malaria
79
MALINV
Acronym: MALINV
Differential Expression
of Malaria InvasionAssociated Proteins
in the Porozoite: Novel
Vaccination Strategy

Duration: 24 months
Type: STREP
Project website: www.cochin.inserm.fr/
BACKGROUND
In humans, sterile immunity against malaria was only
obtained after exposure to irradiated sporozoites
inoculated by mosquitoes. Recently, antigens by invasion
blood stage parasites have been shown to be expressed by
sporozoites, which leads to the hypothesis that they might
also be involved in sporozoite invasion of hepatocytes.
The three antigens investigated to date may not be
responsible for induction of optimal protective responses.
This would account for the difficulties encountered in
reproducing this sterile long-lasting immunity by current
sub-unit vaccines. It would clearly be desirable to
investigate other pre-erythrocytic antigens.
AIMS
The projects aims were:
a. to list all potential genes within the ebl and rh
families in P. falciparum, P.
b. berghei and P. yoelii. Real-time polymerase chain
reaction (RT-PCR) was performed for each gene on
ribonucleic acid (RNA) purified from all the stages
of these parasites, and the expression profile in
sporozoites determined;
c. to obtain recombinant proteins, peptides and
immunological reagents specific to each gene
product expressed in sporozoites;
d. to characterise the proteins expressed in the
sporozoite using reagents obtained in item 2, above;
e. to obtain transgenic parasite lines in which
sporozoite-expressed genes identified in item 1 are
individually disrupted or knocked out, and to purify
the corresponding sporozoites;
f. to employ the reagents from item 2, to determine the
functional role of each protein in sporozoite invasion;
g. to employ the sporozoites obtained in item 4, to
assess the functional role of each protein during the
lifecycle;
h. to employ the reagents from item 2 and item 4, to
conduct immunisation studies;
i. to conduct a detailed analysis of immune responses
80
PRD-Malaria
resulting from item 7, and derive surrogate markers

of protection.

MALINV characterised the new invasion-associated
sporozoite antigens from three species of Plasmodium
and assessed their role in hepatocyte invasion, to develop
immunogens for vaccination studies and assess their
efficacy against a sporozoite challenge.
Laurent Rnia
Hpital Cochin
Paris, France
Tel: +33-1 40 51 65 07
Partners:
Dominique Mazier
Hpital Piti-Salptrire
Paris, France
Robert Sauerwein
University Medical Centre
Maria M Mota
Instituto Gulbenkian de Ciencia
Oeiras, Portugal
Alan Cowman
Walter and Eliza Hall Institute of Medical Research
Melbourne, Australia
PRD-Malaria
81
TB-VAC
Acronym: TB-VAC
An Integrated Project
for New Vaccines
against Tuberculosis

Duration: 60 months
Type: Article 169
Project website: www.tb-vac.org
BACKGROUND
Tuberculosis (TB) causes about two million deaths a

year, with around 98% occurring in developing countries.
Within these countries, the HIV pandemic has had a major
impact on TB, resulting in an additional one million deaths
per year. With the rise in drug-resistant strains of TB, the
disease may once again become a major threat to Europe.
No effective vaccine is available yet.
TB-VAC expects to deliver the following results via two

tracks:
In recent years, several promising new vaccine strategies

have been developed. This project aimed to integrate
European efforts towards the development of novel
tuberculosis vaccine candidates and forward these
vaccines to small-scale phase 1 human clinical trials
in Europe and Africa. Under the coordination of the
Animal Sciences Group in Lelystad, Netherlands, the
project joined 33 leading European institutions from nine
European and four African countries, including two major
vaccine producers.
Optimised production of new and selected vaccines

by combining the best delivery system/adjuvant
available with the best antigen or antigens known.
Definition of robust correlates of protective immunity
against M. tuberculosis and surrogate markers of
TB disease for monitoring and developing effective
TB vaccines.
Evaluation of the efficacy of various selected
vaccine candidates and their associated responses
to mycobacteria and various mycobacterial
components.
AIMS
The main aims of the project are:
the discovery and development of new tuberculosis vaccine
candidates effective in the young adult population;
the development of tests that predict vaccine
efficacy in humans;
the clinical evaluation of lead candidates in small
initial trials in Europe and Africa;
capacity building in developing countries for clinical
evaluation of vaccines;
liaising with other consortia to coordinate specific
activities;
liaising with the European and Developing
Countries Clinical Trials Partnership (EDCTP) to
enable further large clinical trials in Africa.
82
PRD-TB
Track 1: Optimisation of existing vaccine candidates

towards phase I trials:
- Strategic development:
These results should allow the selection of a second

generation of improved vaccines for clinical assessments
in the downstream development component.
- Downstream development:
Production in Europe of promising candidate
vaccines according to international quality
requirements for production.
Establishment of a complete pre-clinical file
to satisfy national and European regulatory
authorities.
Establishment of vertical product development
teams for the most promising candidate-vaccines
to ensure full communication and continued
professional efforts from the upstream vaccine
development down to clinical trials
Phase 1 clinical trials designed and conducted
in three European centres in areas of low TB
endemicity and, later, in three centres of excellence
in endemic areas in Africa.
The results of these studies allowed the selection of

vaccines that could be further clinically developed in
phase 2 trials (for example via the EDCTP).
Track 2: New vaccines/antigen discovery:
Optimisation of live vaccines previously identified
with an efficacy better than BCG.
Discovery of new immuno-modulatory ligands for
improved vaccine efficacy.
New candidate sub-unit antigens with a major focus
given to dormancy/latency-associated antigens, the
latter group being of particular interest.
Selected vaccine antigens (those with efficacies
as good as BCG) will be optimised (particularly by
combining selected antigens) and evaluated for
efficacy in Track 1.
PRD-TB
83
Jelle Thole
Animal Sciences Group
Lelystad, Netherlands
Tel: +31-3 20 23 85 08
S H E Kaufmann
MaxPlanck Institute for Infection Biology
Munich, Germany
F Poccia
National Institute for Infectious Diseases
Rome, Italy
Partners:
PRD-TB
H Wagner / R Lang
Technical University of Munich
Munich, Germany
Paul Lambert
University of Geneva
Geneva, Switzerland
84
S Stenger
University of Erlangen
Erlangen, Germany
F Mascart
Brussels, Belgium
F Dieli
University of Palermo
Palermo, Italy
P. Mettens
GSK Biologicals
Rixensart, Belgium
S Mboup
Hpital le Dantec
Dakar, Senegal
P Andersen
Copenhagen, Denmark
C Martin
Universidad de Zaragoza
Zaragoza, Spain
H. Engers
Armauer Hansen Research Institute
Addis Ababa, Ethiopia
F Sallusto
M Daff / G Puzo / F Altare

Paris, France
C A Siegrist
University of Geneva
Geneva, Switzerland
C Locht / J J Fournie / M Bonneville

Institut National de la Sant et de la Recherche Mdicale
Paris, France
G De Libero
University Hospital of Basel
Basel, Switzerland
J Westermann
University of Lbeck
Lbeck, Germany
F Spertini
Centre Hospital Universitaire Vaudois
B Gicquel / S Cole
Institut Pasteur
Paris, France
T Ottenhoff
Leiden University Medical Centre
Leiden, Netherlands
A Thomas / F Verreck
Biomedical Primate Research Center
R Brookes
MRC Gambia
Banjul, Gambia
M Ota
University of Birmingham
Birmingham, England
UK
Oxford, England
UK
H Dockrell
London School of Hygiene and Tropical Medicine
London, England
UK
A Rawkins
Health Protection Agency Porton Down
Salisbury, England
UK
G. D Hussey
University of Cape Town
Cape Town, South Africa
S Stenger
Universitatsklinikum Ulm
Ulm, Germany
Y Perrie
Aston University
Birmingham, England
UK
E Bell
Manchester University Medical School
Manchester, England
UK
B D Robertson
Imperial College of Science
London, England
UK
K B Walker
National Institute for Biological Standards and Control
Potters Bar, Herts, England
UK
AVS Hill/ H McShane
PRD-TB
85
Neotim
Acronym: Neotim
Innate and adaptive

immunity in clinical
and experimental
mycobacterial infection
in neonates and infants

Duration: 36 months
Type: STREP
Starting date: 1 November 2005
Project website: www.euprojekt.su.se/index.php/
kb_1/io_1307/io.html
BACKGROUND
It is estimated that over two million people worldwide

die each year from tuberculosis (TB), a major infectious
disease that most commonly attacks the lungs. Most
frequently TB is a disease that affects adults, but the
proportion of paediatric TB is expanding. Due to its
chronic nature, the disease is still prevalent in childhood,
including the neonatal period. A significantly increased
pool of knowledge is required in regards to the immune
protection of neonates and children against Mycobacterium
tuberculosis. New insight may allow for combined targeting
of innate and adaptive immune systems highly relevant
in the rational design of vaccines.
The Neotim consortium expects the results to provide

a conclusive assessment of the role and regulation of
the neonatal/infant immune system in determining the
outcome of mycobacterial infections. The data obtained
during the project will also determine whether the use
of selected mycobacterial antigens, together with innate
immunomodulatory molecules, will offer significant protection against human tuberculosis.
AIMS
The Neotim project aims to compare neonates/infants
and adults in terms of protective responses generated
during mycobacterial infections or vaccination with novel
mycobacterial antigens in murine experimental systems
and in humanised mice (reconstituted with human
lymphoid and myeloid cellular populations). The following
activities are being conducted:
comparing innate and adaptive immune responses,
with an emphasis on dendritic cells and T-cells;
investigating neonatal and adult mice during
mycobacterial infection and following inoculation
of a novel and promising candidate vaccine,
methylated HBHA;
investigating such responses using mice
reconstituted de novo with human lymphoid and
myeloid hemopoietic-derived cell lineages (allowing,
for the first time, an experimental dissection of
human immunity to mycobacteria); monitoring and
comparing the immune responses of naturally
infected humans in the corresponding age groups;
investigating the human molecular basis of hypersusceptibility to live BCG in rare neonates with
disseminated BCG disease in order to discover
novel mycobacterial susceptibility genes, which will
then be tested in the humanised mouse model.
86
PRD-TB
Prof. Martin Rottenberg
Microbiology and Tumor Biology Center,

Stockholm, Sweden
Tel: +46-8 24 86 711
Partners:
Carmen Fernandez
Stockholm University
Stockholm, Sweden
Foo Yew Liew

University of Glasgow
Glasgow, Scotland
UK
Jean Laurent Casanova
University of Paris Ren Descartes

Paris, France
Enrico Proietti
Rome, Italy
Camille Locht
Institut Pasteur de Lille
Lille, France
Franoise Mascart
Brussels, Belgium
Mahavir Singh
LIONEX Gmb
PRD-TB
87
Vaccines4TB
Genome - and HLAWide Scanning and

Validation of Cytotoxic
CD8 T Cell Responses
against Mycobacterium
Tuberculosis
Acronym: Vaccines4TB
Duration: 24 months
Type: STREP
Project website: www.biocompetence.eu/index.php/
kb_1/io_3555/io.html
BACKGROUND
Each year, 54 million people are infected with Mycobacterium

(M.) tuberculosis, 6.8 million develop clinical disease, and
2.4 million people die of tuberculosis (TB). Among infectious
diseases, TB is responsible for the greatest number of
deaths (five percent of all deaths worldwide). As such,
vaccinations against TB are urgently required.
The project expected to find new CTL epitopes. More

specifically, it anticipated:
A growing body of evidence from animal studies indicates

that CD8 T cells are involved in the control of latent M.
tuberculosis infection. However, relatively little has been
published on the functional role of mycobacteria-specific
CD8 T cells in humans, nor on the actual mycobacterial
antigens and epitopes targeted by these killer cells.
AIMS
The specific aims of the project were to:
evaluate the CD8 cytotoxic T cell (CTL) response
repertoire in the human population;
test if expression libraries representing the whole
M. tuberculosis genome can be used for CTL
antigen discovery;
test that the use of immuno-bioinformatics is a fast
and rational approach to CTL epitope identification.
88
PRD-TB
identifying proteins likely to be good antigens, using

expression cloning of M. tuberculosis antigens and
M. tuberculosisderived epitopes seen by patient
CTLs;
predicting which peptides are potential CTL
epitopes within all M. tuberculosis proteins for all
major human HLA supertypes, and select a fraction
of these for actual synthesis and test;
measuring binding to HLA molecules for the
predicted peptides;
measuring CTL responses against predicted
epitopes in M. tuberculosis infected persons
and BCG vaccinated individuals using either: (1)
target cells transfected with the M. tuberculosis
expression library and relevant HLA molecules or
(2) target cells pulsed with identified peptides.
Ole Lund
Technical University of Denmark,

Centre for Biological Sequence
Analysis
Building 208
Lyngby, Denmark
Tel: +45-4 52 52 425
Website: www.cbs.dtu.dk
Partners:
Sren Buus
Institute for Medical Microbiology and Immunology Panum
Copenhagen, Denmark
Tom H M Ottenhoff
Leiden University Medical Center
Leiden, Netherlands
Ugur Sahin
Pharmaceuticals AG, Germany
Mainz, Germany
PRD-TB
89
ImmunoVacTB
Acronym: ImmunoVacTB
A New Approach
for Developing a Less
Immunosuppressive
Vaccine for Tuberculosis

Duration: 24 months
Type: STREP
Starting date: June 2007
BACKGROUND
Infections due to Mycobacterium tuberculosis cause over

two million deaths each year. A major problem in combating
tuberculosis is the insufficient efficacy of the current
vaccine, M. bovis BCG. This is due to the fact that BCG
induces the Th2 cytokine IL-4 and the immunosuppressive
cytokine IL-10, apart from the protective Th1 cytokines
Il-12 and IFN. Current data suggest that two
mycobacterial glycolipids lipoarabinomannan (LAM)
and phenolic glycolipid (PGL) play an important role in
this immunosuppression.
The following results are expected:
AIMS
The project aims to find a new strategy to overcome
these known problems of inefficacy, and will design less
immunosuppressive BCG strains, lacking PGL and/or
(parts of) the mannose cap. Immuno VacTB will isolate
BCG strains that lack the LAM mannose cap (or parts
thereof). This will be done in BCG with an intact as well
as with an interrupted pks15/1 gene. These recombinant
single or double mutant BCG strains will be evaluated
in vitro and in vivo for their ability to induce cytokine
production and to protect against tuberculosis in a murine
infection model.
The project will construct novel BCG strains that lack (part
of) the mannose cap of lipoarabinomanan and/or cannot
produce phenolic glycolipid. These strains will be an interesting platform from which to introduce M. tuberculosis
genes encoding important antigens, or non-mycobacterial
genes that enhance an immunoprotective response.
90
PRD-TB
construction of BCG mutants that cannot synthesise

(part of) the mannose cap of LAM and/or PGL;
determination of the structure of LAM and PGL in
the mutants;
determination of the effects of the mutations on
cytokine production by human DCs and T cells as
well as murine macrophages in vitro (the same
experiments will be performed with purified LAM);
determination of the effect of the mutations on
protection against murine tuberculosis in vivo.
It is hoped that new and improved insights will
also be gained into how the immune system is
manipulated by mycobacterial glycolipids, with
the aim of developing an improved M. bovis BCG
vaccine.
As of april 2008: the capless LAM mutant, the PGL mutant
and the double mutant have been constructed in BCG.
The in vivo testing of these strains by the Porto group is
under way.
Bernard A M van der Zeijst
Netherlands Vaccine Insitute
Bilthoven, Netherlands
Tel: +31-3 02 74 41 64
Partners:
B J Appelmelk
VU University Medical Center
Rui Appelberg
Institute for Molecular and Cell Biology
Porto, Portugal
Germain Puzo
Institut de Pharmacologie et Biologie Structurale
Toulouse, France
PRD-TB
91
FLUVACC
Acronym: FLUVACC
Live Attenuated
Replication-Defective
Influenza Vaccine

Duration: 60 months
Type: IP
Starting date: 1 September 2005
Project website: www.greenhillsbiotech.com/
eu_projects.html
BACKGROUND
Industrial production of influenza vaccine still relies on

traditional techniques. Essentially, chicken eggs are used
as mini vaccine factories. They are injected with live
influenza virus, and incubated for several days so that the
virus can multiply. The egg is then opened, and the virus
is harvested, purified and inactivated. Unfortunately, highly
pathogenic avian viruses do not grow well in eggs as they
tend to kill the embryo. There are many other problems
associated with egg-based production. Since the whole
process is time-intensive and hard to scale up, it may be
difficult for supply to meet demand during a pandemic. In
addition, the combination of vaccine with egg proteins can
lead to allergic reactions in some people. FLUVACC aims to
shift vaccine production away from the traditional methods,
with the generation of live attenuated-replication deficient
vaccines that can be produced in cell culture. Instead of
using egg-produced viral proteins, the live attenuated
vaccines developed by the FLUVACC consortium contain
whole replication deficient viruses that generate a strong
immune response, but that are non-pathogenic.
The FLUVACC vaccine will contribute to the efforts to

prevent and control influenza. The proposed vaccine will
reduce mortality and morbidity rates, lost workdays and
hospitalisations.
AIMS
The aim of this project is to develop a novel vaccine
against influenza. This vaccine is a novel component of
European systemic efforts to prevent and control influenza,
based on a replication deficient virus that is generated by
a specialised technique known as reverse genetics. The
vaccine will be produced in cell culture.
Another important aim is to improve core technology for live
attenuated vaccine production, using a technique called
reverse genetics. The project has developed a master
strain that is lacking the NS1 gene which is essential
for productive viral replication. Candidate vaccines for
emerging influenza subtypes can be quickly produced by
inserting their genes into this master strain so that they
express the immunogenic surface proteins, but remain
replication-deficient. This master strain was adapted to
grow to high titers in tissue culture, making it possible to
produce large quantities in the case of a pandemic.
92
EE-FLU
Joachim Seipelt
AVIR Green Hills Biotechnology AG

Vienna, Austria
Tel: +43-1 42 77 61 610
Partners:
Bert Klebl
GPC Biotech AG
Munich, Germany
Ale trancar
BIA Separations d.o.o.
Ljubljana, Slovenia
Martin lais
BioTest Ltd
Konrovice, Czech Republic
Oleg I Kiselev
Russian Academy of Medical Sciences
St Petersburg, Russia
Michael Bergmann
Vienna University Medical School
Vienna, Austria
Thorsten Wolff
Robert Koch Institute
Berlin, Germany
Maria Weidinger-Moser
Weikom & Network Communications Agency
Vienna, Austria
EE-FLU
93
FluVac
Dose Sparing
and Increased
Immunogenicity
for Vaccination
against Pandemic
Influenza with
CoVaccine HT

Duration: 48 months
Type: STREP
Starting date: 1 October 2007
Project website: www.fluvac-project.eu.
BACKGROUND
The risk of a new influenza pandemic is emphasised

by a WHO report documenting several hundred recent
cases of human infection with a new virus strain and an
approximately 50 % mortality rate. On a global scale,
the impact of an influenza pandemic can be enormous,
and a pandemic outbreak could have serious social and
economic consequences on human life, as well as place
a large burden on healthcare systems. High costs of antiinfluenza drugs and their limited availability has revealed
an urgent need for an affordable vaccine for the prevention
and control of an outbreak.
The FluVac project and subsequent development and

registration of the vaccine will have great benefits for the
health of the European population. It will also contribute to
the development of a novel generation of adjuvants and of
improved vaccines to combat infectious diseases.
AIMS
This project is aiming at a novel influenza vaccine
formulation by combining CoVaccine HT and H5N1.
Feasibility studies with the adjuvant have indicated that
CoVaccine HT is a promising candidate for emergency
vaccines to establish high levels of immunity and to
compensate for the limited availability of antigen. The
ultimate goal is to prove the safety and efficacy of a
CoVaccine HT adjuvanted pandemic whole H5N1 virus
vaccine in humans, and to gain insight in its performance
in animal models.
Another objective is to exploit cell culture technology
for antigen production, as this method is more flexible,
independent of supply of animal-derived materials and
more consistent.
It will also target the delivery of a prototype emergency
vaccine to control or prevent a pandemic. In preclinical
and clinical studies, the project will test optimal doses
of inactivated, cell culture-derived whole influenza virus
(H5N1) and CoVaccine HT as adjuvant. The novel
adjuvant CoVaccine HT has been shown to elicit high
humoral and cellular responses against different types
of antigens (including the inactivated influenza virus) in
different animal species. It is considered to be a promising
candidate for a pandemic influenza vaccine.
94
Acronym: FluVac
EE-FLU
Luuk A.Th. Hilgers
Nobilon International B.V.
Boxmeer, Netherlands
Tel: +31-0 48 55 87 276
Project Manager:
Jacco G M Heldens
Nobilon International B.V.
Partners:
James Glover
Protherics plc
The Heath Business and Technical Park
Runcorn, England
UK
Ingileif Jnsdttir
University of Iceland
Reykjavik, Iceland
John S Oxford
Retroscreen Virology Ltd
London, England
UK
Guus Rimmelzwaan
Erasmus Medical Center
EE-FLU
95
PANFLUVAC
Acronym: PANFLUVAC
Efficacious Vaccine
Formulation System
for Prophylactic
Control of Influenza
Pandemics

Duration: 48 months
Type: STREP
Project website: www.panfluvac.org
BACKGROUND
Influenza epidemics remain a burden for both human

health and national economies, as witnessed by the recent
advance of the pathogenic avian H5N1 influenza virus.
For a truly efficacious vaccine, one must consider the
route of virus entry into the host (the respiratory tract), and
host requirements for protective immune defences. While
parenterally-administered inactivated influenza vaccine
is the best prophylactic control measure, parenteral
vaccination does not ensure induction of local immunity in
the respiratory tract the route by which the virus infects
humans and from where it transmits to other individuals.
Inducing mucosal immunity by vaccination would enhance
control of both disease and transmission.
The expected results are:
AIMS
PANFLUVAC aims to produce an efficacious vaccine
formulation to meet immediate and future needs for
controlling influenza epidemics and pandemics. The
project is constructing vaccine delivery systems for
intranasal and parenteral vaccines. New H5N1 vaccines
are to be based on well-established virosome technology
- which has proven its worth for efficacious interpandemic
vaccines - as well as whole virus vaccines. This will permit
a comparison of the intranasal virosomal vaccine with the
whole virus vaccine.
96
EE-FLU
a formulated H5N1 pandemic vaccine developed

from existing technologies and
for preclinical evaluation;
virosomal and whole virion vaccines (existing
technologies) compared in preclinical
evaluations;
evaluated intranasal and parenteral administration;
a pandemic influenza vaccine to meet the current
need for required vaccines in the face of
imminent pandemic influenza threat;
the efficacy of the formulated H5N1 pandemic
vaccine generated from existing technologies
assessed by phase I clinical trial evaluation;
studies in vaccinated subjects in order to generate
a knowledge platform on immunological correlates
and correlates of protection challenged;
an erudite link formulated, joining preclinical and
clinical evaluations;
a dossier prepared on proposed H5N1 vaccines
formulated with novel adjuvants.
Kenneth McCullough
Institute of Virology and Immunoprophylaxis (IVI)

Mittelhusern, Switzerland
Tel: +41-3 18 48 9 361
Partners:
Ronald Kompier
Crucell NV
Leiden, Netherlands
John Wood
Hertfordshire, England
UK
John Oxford
London, England
UK
Lars R. Haaheim
University of Bergen
Bergen, Norway
Maria Zambon
Central Public Health Laboratory
London, England
UK
Isabella Donatelli
Rome, Italy
Carlos Guzman
Hemholtz Centre for Infection Research
Vronique Gobry
SCIPROM
St Sulpice, Switzerland
EE-FLU
97
Intranasal H5vaccine
Acronym: Intranasal H5vaccine
Project number: P5B-CT-2007-044512
Protective Efficacy of
Intranasal del NS1
(H5N1) Influenza Vaccine

Duration: 36 months
Type: STREP
eu_projects.html
BACKGROUND
Avian influenza is now posing a threat to mankind.

Between 2003 and 2006 the WHO reported 161 cases
of avian influenza A of the H5N1 strain in humans; of
these 86 were fatal. At the moment is not clear how the
virus is transferring to humans. Old human influenza
viruses of the H1N1 or H2N2 subtypes could also return
in humans and sooner or later there will almost certainly
be an influenza pandemic unless new and more efficient
vaccines are developed.
The project aims to define an intranasal H5N1 pandemic

vaccine with enhanced capacity to elicit a strong, longlasting local and systemic immune response in humans.
AIMS
The Intranasal H5vaccine project is developing a novel vaccine against avian influenza. It is assessing immunological
properties; conducting preclinical experiments and establishing novel, sensitive methods for the assessment of the
antibody response against viral proteins. These assays will
allow for the selection of an optimal vaccine candidate that
will be subsequently evaluated in clinical trials.
The project will also test the protective properties of the
vaccine against homologous and heterologous influenza
strains in ferret challenge experiments, using different H5
strains. In order to close the gap between the ferret model
and human studies, the project will use the macaque
model to evaluate the immune response. These preclinical
studies will allow the selection of the most potent vaccine
candidate, which will be produced according to cGMP
(current Good Manufacturing Practice) guidelines on Vero
cells. After a toxicological evaluation of the vaccine, clinical
phase I/II studies will be performed. A human challenge
study using the attenuated H5 virus will be carried out,
if permitted by the authorities. Alternatively, for proof of
principle of the del NS technology, an H1-del NS1 vaccine
will be produced and used in an H1 challenge study.
98
EE-FLU
Joachim Seipelt

Vienna, Austria
Tel: +49 38 35 17 250
Partners:
Ivana urov
BioTest Ltd
Volker Wacheck
Vienna, Austria
Jindrich Cinatl
Clinics of J W Goethe-University
Frankfurt, Germany
Nicolai Bovin
Shemyakin Institute of Bioorganic Chemistry
Moscow, Russia
John Oxford
London, England
UK
EE-FLU
99
CHIMERIC VACCINES
Acronym: CHIMERIC VACCINES
del NS1 Virus as

a Vector for
Foreign Antigens

Duration: 30 months
Type: SMEs Cooperative Research Project
eu_projects.html
BACKGROUND
Influenza viruses are species-specific and only rarely

cross the species barrier. Of the hundreds of strains of
avian influenza A viruses, only four are known to have
caused human infections: H5N1, H7N3, H7N7 and H9N2.
These mostly cause mild symptoms, but the exception is
the highly pathogenic H5N1 virus, which has crossed the
species barrier to infect humans in recent years, leading
to the outbreak of avian influenza that began in December
2003. A novel vaccine needs to be developed to provide
protection against avian and seasonal influenza.
Results of this project have shed light on important aspects

in the development of novel vaccination strategies and will
help to further develop the concept of a chimeric vaccine. In
addition, important information regarding immunogenicity
and safety is being generated, and a process for the
production of purified viruses established.
AIMS
This project developed a novel approach for a vaccine.
The technology was based on the insertion of selected
epitopes into a genetically modified influenza virus that is
apathogenic. To achieve these results, the project identified
both a stable vector and promising antigens. Antigen
selection was based on bioinformatics methods that were
substantiated by experimental validation. The properties
of the backbone vector in terms of safety and stability
were assessed in preclinical experiments and gave highly
satisfactory results. To bring the proposed chimeric vaccine
into clinical trials, a production process in small scale was
established, using a novel purification technology.
100
EE-FLU
Joachim Seipelt
Avir Green Hills Biotechnology AG

Vienna, Austria
Partners:
Emergentec Biodevelopment GmbH
Vienna, Austria
BioTest Ltd
Ljubljana, Slovenia
Frankfurt, Germany
Vienna, Austria
State Institution Research
Institute of Influenza
St Petersburg, Russia
EE-FLU
101
Universal Vaccine
Acronym: Universal Vaccine
Novel Antigen -Adjuvant

Vehicle as an Effective
Influenza Vaccine

Duration: 24 months
Type: SMEs Cooperative Research Project
Project website: www.universalvaccine.org
BACKGROUND
One of the biggest problems in trying to develop reliable

influenza vaccines is that flu viruses tend to mutate
frequently. Influenza vaccines work by stimulating
the bodys immunity against the haemagglutinin and
neuraminidase proteins on the viruss surface. But there
is a third protein - M2 - that until now has not been the
focus of much attention. The extracellular domain of this
protein, M2e, has been remarkably conserved in the amino
acid sequence since the human influenza virus was first
isolated in 1933. Scientists are focusing on this protein as
a possible breakthrough for a universal vaccine. If it could
stimulate an adequate immune response, it might be
possible to develop a broadspectrum vaccine against all
influenza A subtypes. Previous research has shown that
when the extracellular domain of M2 (M2e) is linked to
appropriate carrier particles, such as the hepatitis B virus
core, it becomes highly immunogenic.
The expected result was the development of an efficacious,

innovative, safe and easily-administered nasal vaccine for
humans that provides lifelong protection against influenza.
AIMS
The project aimed to:
utilise the M2e peptide as antigenic determinant;
develop a powerful, new, safe and easilyadministered nasal vaccine for humans that
provides lifelong protection against influenza;
covalently fuse the M2e-peptide with the CTA1-DD
adjuvant, creating a strongly immunogenic influenza
vaccine suitable for mucosal delivery;
further improve vaccine efficacy by incorporating
the fusion protein in proprietary liposomes;
increase the in vivo maintenance of the antigen
by using blocked or constrained peptides or
peptidomimetics;
determine the in vivo mechanism of action of the
mucosal influenza vaccine;
demonstrate the safety and efficacy of the vaccine
in animal challenge models.
102
EE-FLU
Anna Ramne
Biovitrum AB
Gteborg, Sweden
Tel: +46-0 31 74 91 118
Partners:
Hans Langedijk
Pepscan Systems BV
Roger New
Royal Veterinary College
London, England
UK
Doriano Cingolani
Eurogentec SA
Seraing, Belgium
Walter Fiers/Xavier Saelens
Flanders Interuniversity/Ghent University
Ghent, Belgium
Nils Lycke
Gteborg University (UGOT)
Gteborg, Sweden
EE-FLU
103
HEPACIVAC
Acronym: HEPACIVAC
New Preventative
and Therapeutic
Hepatitis C Vaccines:
From Preclinical
to Phase I

Duration: 60 months
Type: IP
Project website: www.altaweb.eu/hepacivac
BACKGROUND
AIMS
Liver disease caused by the hepatitis C virus (HCV) infection

affects an estimated 123 million people worldwide. No vaccine
is available and the best antiviral therapy, a combination of
interferon alpha and ribavirin, is only effective in a minority of
patients. A growing body of data suggests that virus-specific
T cell responses are associated with clearance of HCV in
acutely infected humans and chimpanzees.
The long-term objective of the HCV vaccine programme

is to develop both prophylactic and therapeutic vaccines
that elicit antiviral CD4+ and CD8+ responses, capable of
doing one of the following:
The first vaccine candidate is gene based, encodes for the

2 000 amino acid-long HCV Non Structural region (from
NS3 to NS5B) and utilises adenoviral vectors for delivery.
These vectors have been shown to elicit potent CD4+ and
CD8+ T cell responses in rodents and primates. Recently,
a proof-of-concept vaccination and heterologous challenge
experiment in chimpanzees showed that potent, broad
and long-lived T cell responses to HCV were elicited in
vaccinated animals. The gene-based vaccine protected
against acute and chronic disease, induced by a challenge
with a high dose of a heterologous HCV strain. The
second vaccine candidate consisted of recombinant HCV
glycoproteins, gpE1 and gpE2, which were associated to
resemble a pre-virion envelope structure.
Protection against homologous and heterologous challenge,
mediated by CD4+ T cell response and antibodies, was
observed in experiments with chimpanzees. The findings
showed that both vaccine candidates have the potential to
protect humans from a large number of viral strains. The
complementary action of these vaccines might be extremely
instrumental in making a vaccine against HCV, which is
able to stimulate several components of the immune
system and to elicit efficacious immune responses, both in
preventative and therapeutic vaccination settings.
104
EE-Hepatitis
reducing the rate of incidence and/or persistence of

HCV infection following exposure (for a prophylactic
vaccine);
increasing the rate of clearance of HCV infection as
a monotherapy, and/or in combination with current
therapy or novel antiviral therapy (for a therapeutic
vaccine).

The HEPACIVAC project will provide the opportunity to
analyse immune correlates of protection from HCV infection
in detail, as well as to standardise immunogenicity assays
and to establish benchmark references for future preclinical
and clinical studies of HCV candidate vaccines.
Riccardo Cortese
Krystina Bienkowska-Szewczyk
University of Gdansk
Gdask, Poland
The Egyptian Company for Diagnostics

Giza, Egypt
CeInge Biotechnologie avanzate s.c.a.r.l.

Naples, Italy
Scientific Coordinator:
Sayed F Abdelwahab
Sergio Abrignani
Novartis Vaccine & Diagnostics
Siena, Italy
Cristiana Tozzi
ALTA S.r.l.
Siena, Italy
Adrian Hill
Oxford, England
UK
Partners:
Alfredo Nicosia
Istituto di Ricerche di Biologia Molecolare P. Angeletti
Rome, Italy
Ferruccio Bonino
Fondazione IRCCS Ospedale

Maggiore Mangiagalli e Regina Elena
Milan, Italy
Albert D M E Osterhaus
Erasmus Medical Centre
Geert Leroux Roels
University of Ghent
Ghent, Belgium
Jane McKeating
University of Birmingham
Birmingham, England
UK
Stefan Zeuzem
University of Saarland
Saarland, Germany
EE-Hepatitis
105
DISSECT
Acronym: DISSECT
Development
of Intervention
Strategies against
SARS in a EuropeanChinese Taskforce
Project number: SP22-CT-2004-511060

Duration: 36 months
Type: STREP
Project website: www.cnb.uam.es/~webcoron/
EUprojectdissect/
BACKGROUND
Severe Acute Respiratory Syndrome (SARS) was
initially detected in Guangdong province, China. It has
been proven that the etiological agent of SARS is a new
coronavirus (CoV) with the acronym SARS-CoV.
The recent outbreak constitutes an important challenge to
the capabilities of EU Member States, and confirms that
new communicable disease outbreaks require a specific
focus. Actions should attempt to address longer term
research commitments, define appropriate sustainable
priorities and encourage collaboration with partners
from SARS-affected areas in third countries. There is
an urgent need to develop strategies for preventive
therapy for healthcare workers, who could eventually be
vaccinated, and then for other target groups who should
be vaccinated.
The emergence of SARS has created serious economic
and societal problems in China, reducing human and
commercial interaction. The project created a EuropeanChinese task force to combat SARS, and create essential
links between two parts of the world.
AIMS
This project encompasses all the complementary aspects
necessary for the development of intervention strategies,
including vaccination, immunotherapy, and antivirals
to protect against SARS. In addition, techniques and
materials will be generated to develop diagnostic kits that
will lead to the identification of infected individuals at very
early steps of the disease, and to differentiate between
vaccinated and naturally infected people. The first focus
of the project is vaccine development. Accordingly, a set
of complementary strategies is proposed to guarantee the
success. These strategies include classical vaccines
(such as whole inactivated virus), subunit vaccines,
and state of the art-recombinant technology derived
vaccines. The second focus of the project is on the state
of the art-therapeutic approaches, ranging from the use of
monoclonal antibodies to specific antivirals. For achieving
106
EE-SARS
the primary objectives of this project, the availability of

an adequate preclinical setting for SARS-CoV research,
including animal models, as well as the access to relevant
clinical samples are absolute preconditions. These all met
in this project, as a result of the expertise of the individual
groups involved. To develop this comprehensive project,
laboratories from the European Union and China are
collaborating. The laboratories from EU member states
(Spain, UK and The Netherlands) have a long-term
experience (more than twenty years) in coronavirus
pathology, immunology and molecular biology. The
groups from China have key knowledge on the onset and
evolution of SARS, high technology, and have generated
large collections of biological materials: viruses, sera,
tissues, clinical and epidemiological data.

A. PRODUCTION OF SARS-CoV ANTIGENS IN
DIFFERENT EXPRESSION SYSTEMS. Significant
progress has been done on the expression of viral proteins
(including S, S1, S2, M, E, N, 3a, 6, and 7a) in different
systems (bacteria, mammalian cells, baculoviruses,
yeast and plants). Several SARS-CoV antigens providing
protection against SARS-CoV have been produced in
different expression systems.
B. PRODUCTION OF A RECOMBINANT VACCINE FOR
SARS-CoV. The construction of a recombinant vaccine
for SARS-CoV has been one of the most successful
outcomes of the project. The efficacy of this vaccine has
been shown in two animal model systems, hamsters and
transgenic mice.
C. A SARS-CoV replicon that is self-amplified with
high efficiency has been constructed. This replicon will
be very useful to screen anti-virals without the need to use
infectious virus.
D. Development of an inactivated SARS-CoV vaccine.
The attenuated rSARS-CoV engineered is an excellent
starting point for the production of a chemically inactivated
vaccine. This development has important practical
applications, as inactivated vaccines are safer and could

be applied immediately in the event of a reemergence of
SARS-CoV
E. Role of accessory 3a, 6 and 8 proteins in virus host
interaction. Following the discovery and characterization
of 3a protein O-glycosylation, which was meanwhile
published, it was established that this protein interacts
with the viral M protein, though this interaction is weak.
The evolution and processing of ORF 8 has been studied.
Protein 6 has been involved in replication.
F. DEVELOPMENT OF ANIMAL MODEL SYSTEMS TO
EVALUATE PROTECTION AGAINST SARS. Both ferret
and macaque have been developed as animal models
for SARS-CoV, and these models have been refined and
characterized.
G. DEVELOPMENT OF SARS-CoV DIAGNOSTIC SYSTEMS. An APEX microarray system to diagnose respiratory viruses, including SARS-CoV has been developed.
Partners:
Juan Antonia Garcia

Centro Nacional de Biotecnologia, CSIC
Madrid, Spain
Qi Xie
Institute of Genetics and Developmental Biology
Beijing, China
Peter J. M. Rottier
Utrecht University
Utrecht, Netherlands
Albert DME Osterhaus
Erasmus University Rotterdam
Anlong Xu
Sun Yat-sen University
Guangzhou, China
Zhihong Hu
Wuhan Institute of Virology
Wuhan, China
Pilar Perez Brea
Centro Nacional de Microbiologia
Madrid, Spain
Juan Plana-Durn
Fort Dodge Veterinaria SA
Girona, Spain
Luis Enjuanes
Han van den Bosch

Intervet UK Ltd
Milton Keynes, England
UK
Centro Nacional de Biotecnologia, CSIC

Madrid, Spain
Tel: +34-9 15 85 45 55
EE-SARS
107
SARSVAC
Acronym: SARSVAC
Immunoprevention
and Immunotherapy
of SARS Infection
Project number: SP22-CT-2004-511065

Duration: 36 months
Type: STREP
Project website: www.novartis.it
BACKGROUND
The SARS (Severe Acute Respiratory Syndrome) epidemic

of 2003 swept across 30 countries, affected a reported
8 422 people, 916 of whom died, and almost completely
paralysed Asias economy. Aggressive quarantine
measures and rising summer temperatures successfully
terminated the first eruption of SARS, allowing doctors
and scientists to consolidate what they learned about the
disease and plan for possible future outbreaks.
In 2004, project partners filed for patent protection for an

innovative killed-virus vaccine that can protect against
SARS coronavirus infections. Commercial availability
is expected in 2014. The project also succeeded in
developing human monoclonal antibodies against SARS
CoV, which can be utilised for passive immunotherapy.
Antibody material has been stored, suitable for animal
and structural studies. Furthermore, project partners
collaborated with the US-based NIH for the development
of a recombinant vaccine based on SARS virus-like
particles (VLP) which are non-infectious but can stimulate
the production of antibodies and immune T-cells.
This project was prepared in response to urgent medical

and societal needs for immunopreventive (vaccination)
and immunotherapeutic measures for SARS. An integrated
strategy for developing effective vaccines and for
establishing effective therapeutic treatment was developed.
The strategy for vaccine development followed two parallel
approaches: i) the preparation of a classical inactivated
vaccine (as already done for other coronaviruses), ii)
the definition of potential antigens and T/B protective
epitopes through the study of SARS-CoV derived viruslike particles (VLP), pivotal to the understanding of
SARS-CoV morphogenesis and virion maturation. The
immunotherapeutic strategy relied on development and
validation of neutralising human antibodies to SARSCoV. Under this project, academia experts in immunology,
vaccinology, and molecular biology joined forces with
industrial vaccine production experts, in order to develop
preventive and therapeutic measures for SARS.
AIMS
The project aimed to produce an efficacious vaccine
formulation to meet immediate and future needs
for protection against SARS infections as well as
immunotherapeutic measures for SARS.
108
EE-SARS
Mariagrazia Pizza
Novartis Vaccines and Diagnostics S.r.l.

Siena, Italy
Tel: +39-0 57 72 43 545
Partners:
Stephan Becker
Philipps-Universitat Marburg
Marburg, Germany
Antonio Lanzavecchia
Istituto di Ricerca in Biomedicina
Peiying Ouyang Peiying
Fudan University
Shanghai, China
EE-SARS
109
SARS/FLU VACCINE
Acronym: SARS/FLU VACCINE
Development of a
Combined Influenza/
SARS Vaccine

Duration: 36 months
Type: STREP
eu_projects.html
BACKGROUND
In 2002, an atypical pneumonia, characterised by progressive respiratory failure, emerged in southern China. The
causative agent was rapidly identified as a new coronavirus designated as Severe Acute Respiratory Syndromeassociated virus SARS-CoV. The disease swept rapidly to
neighbouring regions and led to several international cases, including Canada. By the end of the epidemic, in July
2003, about 8 000 SARS cases and almost 800 deaths
due to SARS were recorded worldwide. Since then, the
world is in an inter-epidemic period, as no new cases have
been reported.
It is hoped that the project will result in a SARS/flu

vaccine that has the potential to induce protective immune
responses against SARS-CoV and the influenza virus with
one immunisation.
AIMS
The aim of the project was to test constructs for
immunogenicity. The ones that provoke the best immune
response without compromising safety in animal testing
will be selected for a full preclinical testing programme.
110
EE-SARS+FLU
Thomas Muster

Vienna, Austria
Tel: +43-1 31 99 670
Partners:
Jindrich Cinatl
Frankfurt, Germany
Ale trancar
Ljubljana, Slovenia
Bernd Mayer
Emergentec Biodevelopment GmbH
Vienna, Austria
Ivana urov
BioTest Ltd
Joachim Seipelt
University of Vienna Medical School
Vienna, Austria
EE-SARS+FLU
111
NOVADUCK
Acronym: NOVADUCK
Novel AI DIVA
Recombinant Vaccines
for Duck
Project number: SSPE-CT-2006-044217

Duration: 36 months
Type: STREP
Project website: www.novaduck.eu
BACKGROUND
AIMS
The ongoing outbreak of highly pathogenic avian

influenza (HPAI) caused by the H5N1 virus has caused
widespread concern as H5N1 can occasionally cross
the species barrier to infect humans. Ducks play a major
role in the epidemiology of avian influenza (AI) because
wild waterfowl, including ducks, constitute the natural
reservoir of all subtypes of influenza A virus. Experimental
infection of ducks with recent isolates indicates a longer
shedding period and a selection for lower virulence
variant, suggesting that duck has become the Trojan
horse of Asian H5N1 Avian Influenza (AI) (Hulse-Post et
al., 2005).
The NOVADUCK project aims to develop and evaluate

new highly protective and cost-effective avian influenza
live vaccines for ducks based on live vectors and in line
with the DIVA strategy. More specifically, it is:
Although biosecurity is the first line of defence against

HPAI, strategic use of vaccination is clearly recognised
as a tool to help eradicate HPAI in an infected country.
Most studies evaluating the efficacy of AI vaccines
have been performed in chickens; duck studies have
been relatively rare. Existing inactivated AI vaccines are
less immunogenic in ducks than in chickens and must
generally be administered twice to be fully efficient. At
present there is no commercially available DIVA test
to monitor AI infection in birds injected with this type of
vaccine. Therefore, highly efficient, cost-effective, DIVAcompatible AI vaccines for ducks are still greatly needed.
In this specific context, live vector-based vaccines hold
the greatest promise and are one of the most effective
options. Indeed, some live recombinant vector-based AI
vaccines have shown excellent results in chickens, but they
are not necessarily adapted for use in ducks. Expected
advantages of this type of vaccine include administration
at a younger age, mass administration, rapid onset of
immunity, and compatibility with the DIVA strategy.
The NOVADUCK project is designed to demonstrate and
exploit the potential of live vector vaccines to develop
a new generation of highly efficient and cost-effective
AI vaccines for ducks and therefore could contribute to
reduce AI from the ecosystem.
112
EE-Avian FLU
identifying the optimal AI immunogenic sequence

(s) to be inserted into the selected live vectors;
generating and optimising three types of live
recombinant vector-based vaccines;
developing reliable and cost-effective duckspecific immunological tools to measure the
immune response induced by the different vaccine
candidates and to detect infection in a vaccinated
duck (DIVA strategy);
assessing the safety and immunogenicity of the
new vectored vaccine candidates and comparing
it with those of existing vaccines to select the best
vaccine candidate(s);
setting up a challenge model in ducks for vaccine
evaluation of efficacy;
measuring the efficacy of the most immunogenic
vectored vaccine candidates against recent HPAI
H5N1 and comparing it with existing vaccines;
studying the effect of vaccination on genetic/
antigenic drift;
selecting the best candidate(s) to be developed
based on its (their) immunogenic and protective
properties as well as its (their) estimated cost of
production and administration mode flexibility (e.g.
individual versus mass administration).

The project is expected to obtain the following results:
Identification of the best viral vector vaccine for
ducks; the immunogenicity of three poxvirus-based
vectors was studied; a second type of vector has
been developed and will be soon assessed in
ducks; the development of a third vector is ongoing;
identification of the optimal AI immunogenic
sequence to be inserted into a vector; a first DNA
vaccination study performed in ducks allowed the
selection of a highly immunogenic AI gene ; a new
study will compare the immunogenicity of additional
AI genes including a gene mix allowing the
generation of retrovirus-based virus-like particles;
development of new tools to evaluate the duck
immune response; reagents and techniques are
currently being developed to evaluate the humoral,
cellular and mucosal immune response induced
by AI vector vaccines in ducks; in particular, DIVA
tests and their compatibility with these vector-based
vaccines are being evaluated;
development of a reproducible AI challenge model
in ducks for vector vaccine efficacy studies;
definition of the minimal level of protection that
should be expected for an acceptable AI duck
vaccine standard for evaluation of efficacy of duck
AI vaccine;
production of data on the effect of vaccination of
ducks on genetic/antigenic drift of the challenge virus;
Dr Michel Bublot
Merial SAS
254 Rue Marcel Mrieux
69007 Lyon, France
Tel:+33 4 72 72 59 73
www.novaduck.eu
Partners:
Dr Vronique Jestin
Agence Franaise de Scurit Sanitaire
des Aliments (AFSSA)
Ploufragan, France
Dr Thierry van den Berg
Veterinary and Agrochemical Research Centre (VAR)
Brussels, Belgium
Dr Csaba Dren
Veterinary Medical and
Research Institute of the HAS (VMRI)
Budapest, Hungary
Dr Vilmos Palfi
Central Veterinary Institute
Budapest, Hungary
Dr Jill Banks
Veterinary Laboratory Agency
Kent, England, UK
Fabienne Mathieu
Biosource Europe
Nivelles, Belgium
Dr Charlotte Dalba
Epixis S A
Paris, France
EE-Avian FLU
113
AIV VACC DIAGNOSIS

Acronym: AIV VACC DIAGNOSIS
Vaccine, Diagnostic
Test Development and
Immunology Aspects
of Avian nfluenza
Project number: SSPE-CT-2007-044141

Duration: 36 months
Type: SSA
Project website: www.aiv-vacc-diagnosis.com
BACKGROUND
The highly pathogenic H5N1 avian influenza currently

circulating in Asia, and recently in northern and western
Africa and Europe, has led to the deaths of more than 150
million birds and 150 humans. Due to the seriousness of
this threat some countries are taking steps to vaccinate
their entire poultry population. Currently a consensus is
emerging that vaccination of birds at risk could be a critical
part of a control strategy in averting a human pandemic.
This project is expected to deliver the first mass

applicable live vaccine against highly pathogenic H5N1
avian influenza. The vaccine would offer major technical
advantages, including production aspects, over the
currently existing vaccines.
Although very useful in the fight against avian influenza, all

currently available influenza vaccines have considerable
shortcomings. Several vaccines developed over the
past two decades to protect poultry against the highly
pathogenic H5 or H7 are based on inactivated whole virus
vaccines. Apart from the challenge of setting up a robust
diagnostic test for differentiating vaccinated from infected
animals, these vaccines have to be administered by labour
intensive and expensive parenteral injections.
AIMS
The primary aim of this project is to develop better
avian influenza vaccines through live or vector vaccines
that could be mass applicable through spray, drinking
water or eye drops. These vector vaccines would offer
considerable advantages - mass applicable, less labour
intensive and animal friendly application, protection by
local and systemic immunity and less interference with
eventual maternal antibodies, more complete protection
through cellular and humoral immunity, faster onset of
immunity when used in face of an outbreak and cheaper
production methods.
114
EE-Avian FLU
The development of molecular biological tools will allow in

the future a quicker response to changes in antigenicity of
the field-virus. The construction of gene cassettes that will
allow fast integration of the H region of future genetically
and antigenically different influenza strains in the ND
vector will allow a much faster response for construction
of updated vaccine strains.
Dr Danny Goovaerts
Intervet International bv
Wim de Krverstraat 35
P.O. Box 31
Tel: +31-4 85 58 77 27
Partners:
Dr Thomas Mettenleiter
Friedrich-Loeffler-Institut
Federal Research Institute for Animal Health
Greifswald-Insel Riems, Germany
Dr Christian Schelp
Bommeli Diagnostics
Leibefeld-Bern, Switzerland
EE-Avian FLU
115
SCOOTt
Acronym: SCOOTT
Sustainable Control
of Onchocerciasis
Today and Tomorrow
Project number: INCO-CT-2006-032321

EC contribution: 2.8 million
Duration: 48 months
Type: STREP
BACKGROUND
Onchocerciasis (river blindness) is caused by the filarial

nematode Onchocerca volvulus, which is transmitted
through the bite of blackflies. Currently it afflicts 37 million
people, 95% of whom live in West and Central Africa.
Control relies on mass treatment with ivermectin. However,
this neither kills adult worms nor permanently stops
microfilarial production. Furthermore, there is emerging
resistance, and in areas where loiasis (Loa loa) is also
endemic ivermectin cannot be used for mass treatment
because of the risk of allergic reactions. An alternative
may be tetracyclines whose activity is directed against
Wolbachia, an endosymbiont bacteria that has been
discovered in Onchocerca spp. L loa does not possess
Wolbachia, so tetracyclines would provide a safe therapy
in loiasis-endemic areas.
It is hoped that the project will:
Experiments performed with the O. ochnegi cattle

model and Litomosoides sigmodontis mouse models
have demonstrated the feasibility of vaccination against
filarial parasites. These models, with the human studies,
have identified the key effector mechanism of protective
immunity. Work is now focused on identification of the
protective [vaccine] antigens.
AIMS
The aims of the project are to improve sustainable control
of onchocerciasis through:
refinement of existing chemotherapeutic regimes
by use of doxycycline to complement ivermectin
treatment and further screening of existing drugs;
assessment of immunological sequelae of
ivermectin intervention and their implications for
improved control strategies;
identification of new targets, including vaccine
candidates, and approaches for integrated control.
116
NID-Helminth
establish processes for effective communitydirected treatment of onchocerciasis with

doxycycline;
determine efficacy and feasibility of using
doxycycline for treatment of onchocerciasis;
determine the impact of ivermectin and doxycycline
treatment on immune responses of humans and in two
animal models (O ochengi in cattle and Litomosoides
sigmodontis in mice);
identify mechanisms of protective immunity in two animal
models (O ochengi in cattle and Litomosoides sigmodontis
in mice);
assess the impact of drug treatment on protective
immune responses in the two animal models;
identify vaccine antigen candidates.
Prof. David W Taylor
Centre for Infectious Diseases

University of Edinburgh,
Edinburgh, Scotland
UK
Tel +44-0 13 16 50 79 96
Email: [email protected],
Prof. Hartwig Schulz-Key

Eberhard Karls Universitaet
Tuebingen, Germany
Prof. Odile Bain / Dr Coralie Martin
Museum National dHistoire Naturelle Ecologie

& Gestion de la Biodiversite
Paris, France
Partners:
Prof. Judith E Allen

University of Edinburgh
Edinburgh, Scotland
UK
Dr Samuel Wanji
Research Foundation in Tropical Diseases
Buea, Cameroon
Dr Vincent N Tanya
Instituit de Recherche Agricole pour le Developpement
Ngaoundr, Cameroon
Prof. Ohene Adjei
School of Medical Sciences
Kumasi, Ghana
Dr Meba Banla
Universite de Lome
Sokode, Togo
Prof. Alexander J Trees / Dr Ben Makepeace
Incorporated Liverpool School of Tropical Medicine
Liverpool, England
UK
Prof. Achim Hoerauf
Institute for Medical Microbiology Immunology
and Parasitology
Bonn, Germany
NID-Helminth
117
TRANCHI
Acronym: TRANCHI
T Cell Regulation
and the Control of
Helminth Infections

Duration: 36 months
Type: STREP
Project website: http://tranchi.org
BACKGROUND
Helminth infections are among the most neglected

communicable diseases afflicting developing countries.
Pharmacological treatments are compromised by
rapid re-infection, variable compliance and emerging
resistance. Vaccination has not yet succeeded in evoking
strong resistance. The critical question in helminth control
remains why the immune system fails to clear parasites,
which may be due to the presence of a newly-identified
cell type, the Regulatory T cells (Treg).
The projects results are expected to include:

a database containing all clinical and parasitological data
required.
AIMS
The project will establish whether Regulatory T cells,
lymphocytes with immunosuppressive properties, are
active in chronic helminth infections, and if so, whether
targeting such cells may offer an immunological cure to the
major tropical diseases of filariasis and schistosomiasis. It
will achieve these by carrying out the following:
profiling the type and functions of Tregs in filariasis
and schistosomiasis infected humans;
comparing Treg activity in patient groups of differing
infection status/levels of pathology;
establishing if polymorphisms for regulatory genes
are linked to Treg profiles in humans;
demonstrating the role of Tregs in helminthassociated hyporesponsiveness;
testing whether neutralisation of Tregs restores
immune responsiveness in human cells;
testing whether neutralisation of Tregs restores
immunity to infection in animal models;
characterising human Treg gene expression and T
cell receptor usage;
assessing community and health system issues for
new immunological interventions.
118
NID-Helminth
an understanding of the relationship between Treg

activity and infection status, intensity and pathology
in filariasis and schistosomiasis.
testing the hypothesis that Tregs maintain helminth
infection in animal model systems.
a mini-gene array for expression analysis of genes
associated specifically with Tregs.
simple, accurate and high throughput genotyping
that is user friendly.
molecular gene expression profile of Treg cells.
TCR usage and antigen specificity of Treg cells.
a comprehensive analysis of the extent and
patterns of polymorphisms in regulatory genes in
Indian, Indonesian and African populations.
appraisal of perceptions and attitudes towards new
immunological interventions.
Prof. Rick Maizels
University of Edinburgh, Ashworth Laboratories

Institute of Immunology and Infection Research
West Mains Road
Edinburgh, Scotland
UK
Tel +44-1 31 65 05 511/456
E-mail [email protected]
Partners:
Prof. Maria Yazdanbakhsh

Leiden, Netherlands
Prof. Peter Kremsner

Eberhard Karls Universitt Tbingen
Tbingen, Germany
Dr Taniawati Supali
University of Indonesia - Faculty of Medicine
Jakarta, Indonesia
Dr Balachandran Ravindran
Institute of Life Sciences
Bhubaneswar, India
Dr Rahmah Noordin
Universiti Sains Malaysia
Penang, Malaysia
Dr Elie Mavoungou
Hopital Albert Schweitzer - Medical Research Unit
Lambarn, Gabon
NID-Helminth
119
BOVAC
Development of a
Prophylactic Vaccine
and Diagnostic Markers
to Diagnose and Prevent
Lyme Borreliosis
Specific to Europe and
North America

Duration: 30 months
Type: STREP
Project website: www.bovac.org
BACKGROUND
Lyme disease or borreliosis (LB) is the commonest tickborne disease in Europe. It can be transmitted to humans
when they are bitten by ticks carrying species of the
Borrelia bacterium. Infection is often diagnosed by a rash
(Erythema migrans) that spreads out from the site of the
tick bite. If caught early, the disease can be prevented with
oral antibiotics. However, if left untreated, the bacteria can
spread through the bloodstream, access various tissues
and cause severe diseases including meningitis, arthritis
and carditis. Official incidence rates in Europe range
from 0.3 to 150 cases per year per 100 000 population.
However, few countries have made LB a notifiable
disease, so these rates are only an approximation. Many
experts believe that actual rates of LB infection could be
up to seven times higher.
The key objective of the project was the development of

vaccine candidates effective against LB. The consortium
identified more than 100 novel antigens using the
ANTIGENome technology and identified first candidates
in an animal model of LB infection. Furthermore, the
epidemiologic studies revealed novel insights into the
infestation of ticks by LB and other pathogens on a
country-wide level. The obtained results build a strong
basis for the further development of an LB vaccine.
No vaccine exists for the European version of the disease,

despite the fact that in some countries the disease has had
a significant socioeconomic impact. Innovative technology
was applied in this project by several jEuropean SMEs and
universities, to identify and isolate antigens common to
all Borrelia species causing borreliosis. The project used
state-of-the-art molecular biology techniques, namely
the ANTIGENome technology, to identify and isolate
prospective antigens.
AIMS
The aim of the project was to select novel vaccine
candidates suitable to develop a vaccine to prevent
LB. The consortium was also interested in using the
identified antigens to evaluate their use in developing
novel diagnostic tools for LB as well as assessing the
importance of LB in Austria and the Czech Republic by a
thorough epidemiology study.
120
Acronym: BOVAC
NID-Lyme disease
Dr Andreas Meinke
Intercell AG
Campus Vienna Biocenter 5
Vienna, Austria
Tel: +43-1 20 62 02 10
www.intercell.com
Partners:
Dr Martin lais
BioTest S.R.O.
Prof. Gerold Stanek

Medical University of Vienna
Vienna, Austria
Dr. Jutta Huber
MWG Biotech AG
Ebersberg, Germany
Prof. Bohumir Kri
National Institute of Public Health
Prof. Sven Bergstrom
Ume University
Ume, Sweden
NID-Lyme disease
121
SAVINMUCOPATH
Acronym: SAVINMUCOPATH
Novel Therapeutic
and Prophylactic
Strategies to Control
Mucosal Infections
by South American
Bacterial Strains

Duration: 36
Type: STREP
eu_projects.html
BACKGROUND
Enteric and respiratory diseases cause many thousands

of deaths worldwide. Bacteria that invade the enteric
and respiratory mucosa are the focus of this project and
in particular Streptococcus pneumoniae, Salmonella
enteritidis and Bordetella pertussis which are associated
with serious rates of morbidity and mortality, especially
in young children and low socio-economic status people.
These infectious strains are unique to Latin America and
the scientific community has neglected development of
specific therapies and vaccines.
The expected result is identification of molecules from

the selected bacteria that activate specifically protective
mucosal innate immunity to block the infections at the
port of entry of bacteria and stimulate antigen-specific
responses through mucosa. The project also hopes to
define the signature of innate protection against the
selected pathogens.
AIMS
The main aims of the project are to gain understanding
of the host-pathogen interaction and to develop novel
mucosa-specific therapeutics and vaccines to control
bacterial infections. Innate defences are up-regulated
at mucosal sites upon detection of conserved microbial
molecules and contribute both to the immediate barrier
function to mucosal colonisation and the long lived
antigen-specific mucosal immune responses. These
molecules thus have early immunostimulatory activities
and adjuvant properties on mucosa. The projects strategy
is to take advantage of these natural mechanisms to
improve clearance and immunoprophylaxis against the
selected life-threatening pathogens.
Bacterial strains are being studied in experimental animal
mucosal infection models in order to (i) characterise the
innate mechanisms of early elimination of pathogens and
the concomitant mechanisms of induction of mucosal
adaptive immunity, (ii) define the proof of concept that
conserved microbial molecules can activate mucosal
immunity, and (iii) identify novel mucosa-specific pathogen
molecules with biological activities on mucosal innate and
adaptive immunity using purified bacterial components
and screening on cell and animal models.
122
NID-Respiratory
Dr Jean-Claude Sirard
INSERM U801
Institut Pasteur de Lille - Institut de Biologie
Equipe dImmunit Anti-Microbienne des Muqueuses
1 Rue du Pr Calmette
Lille, France
Tel: +33-3 20 87 10 76
E-mail : [email protected]
Partners:
Martin Rumbo
Laboratorio de Investigaciones
en el Sistema Inmune (LISIN)
La Plata, Argentina
Daniela Hozbor
Instituto de Bioqumica
y Biologa Molecular (IBBM)
La Plata, Argentina
Tracy Hussell
Kennedy Institute of Rheumatology - Imperial College
London, England
UK
Wolf-Dietrich Hardt
ETHZ, Institute of Microbiology
Zurich, Switzerland
Jos Alejandro Chabalgoity
Instituto de Higiene
Montevideo, Uruguay
Alexis Kalergis
Pontificia Universidad Catolica de Chile
Santiago, Chile
Patricia Lopez Biscayart / Augusto Pich Otero
BIOL Instituto Biolgico Argentino
Buenos Aires, Argentina
NID-Respiratory
123
OMVac
Novel Prevention
and Treatment
Possibilities for
Otitis Media through
the Comprehensive
Identification of
Antigenic Proteins
Project number: LHSB-CT-2006-037653

Duration: 36 months
Type: STREP
BACKGROUND
Otitis Media (OM) is one of the most prevalent childhood

diseases and the most common reason for the prescription
of antibiotics. Approximately 80% of all children experience
an episode of acute OM by three years of age. Recurrent
OM affects up to 40% of children and may persist for
periods of weeks to months, causing symptoms ranging
from hearing loss and tinnitus to anorexia or conjunctivitis.
The main causative agents are the bacterial pathogens
Streptococcus pneumoniae, Haemophilus influenzae
(NTHi) and Moraxella catarrhalis, which colonise the
middle ear, often after a primary viral infection. Considering
the high direct and indirect costs of OM, there is an urgent
need for an alternative and effective therapy.
The project expects the following results:
AIMS
The main objective of this project is the identification of
novel vaccine candidates from NTHi and M. catarrhalis
to develop a prophylactic vaccine against OM. Bacterial
surface display libraries will be constructed and screened
with human sera from exposed individuals to define the
ANTIGENome of both pathogens. Following thorough
in vitro validation selected antigens will be evaluated in
experimental animal models of OM.
The project is also addressing the comprehensive
characterisation of natural immune responses against
proteineacous antigens of the major three bacterial
pathogens causing OM. Moreover, the function of
protective antigens during pathogenesis and biofilm
formation will be investigated.
124
Acronym: OMVac
NID-Otitis media
comprehensive identification of antigens from

M. catarrhalis and NTHi, by using Intercells
ANTIGENome technology and complementary
proteomic approaches;
in vitro and in vivo validation of identified antigens
to select the most promising vaccine candidates;
characterisation of protective antigens with respect
to their role in pathogenesis of M.catarrhalis and
NTHi (including biofilm formation);
definition of natural immune responses against the
identified antigens from M. catarrhalis, NTHi and
S. pneumoniae, using the available sera and Ig
preparations.
Andreas Meinke
Intercell AG
Campus Vienna, Biocenter 6
Vienna, Austria
Tel: +43-1 20 62 02 10
Partners:
Andreas J. Kungl
University of Graz
Graz, Austria
Wolfgang Zimmermann
AGOWA GmbH
Berlin, Germany
va Bn
Semmelweis University
Budapest, Hungary
John Hays
Erasmus MC
Peter W.M. Hermans
Radboud University Nijmegen Medical Centre
Birgitta Henriques-Normark
Solna, Sweden
NID-Otitis media
125
HEVAR
Acronym: HEVAR
Herpesvirus-based
Vaccines against
Rotavirus Infections

Duration: 36 months
Type: STREP
BACKGROUND
Diarrhoea caused approximately two million deaths per

year worldwide in the last decade and was responsible
for an estimated 20% of mortality in children aged less
than four years in developing countries. Rotaviruses are
the most common cause of severe dehydrating diarrhoea
in young children in these countries, accounting for 20%
to 60% of hospitalised cases. Rotavirus infection and
disease cannot be controlled by hygiene and sanitation
measures. There is an urgent need for the development
and deployment of an effective prophylactic anti-rotavirus
vaccine that would have universal application as part of
childhood immunisation programmes.
The main deliverables of HEVAR will be a set of toolboxes

containing a large collection of HSV-1-based and DNAbased vectors expressing mouse rotavirus antigens that
will be already evaluated in mice. These toolboxes will
also contain a set of vectors expressing human rotavirus
antigens from strains with epidemiological significance
in South America. All these tools will be accessible to
any academic team wishing to use them for vaccine
development or research on rotaviruses. Knowledge of
the complex technologies required to locally generate,
produce and evaluate the HSV-1-based gene transfer
vectors will therefore be transferred from European groups
to South American partners.
AIMS
The projects aim is to contribute to a better understanding
of the immune biology of rotavirus infections using a novel
generation of gene transfer vectors, as a first step towards
the development of innovative genetic vaccines to fight
against these pathogens. To this end, HEVAR will develop
herpes simplex virus type 1 (HSV-1)-based vectors for the
generation and analysis of rotavirus-specific expression
and display model vaccines. This approach is based
on the possibility of engineering HSV-1-based vectors
expressing and/or displaying rotavirus antigens, either
individually or in combination, alone or together with
immune-modulator genes.
126
NID-Diarrhoea
Dr Alberto Epstein
Universit Claude Bernard Lyon 1

43 Bd du 11 Novembre 1918
Villeurbanne, France
Tel: +33-4 72 43 13 25
E-mail: [email protected] fr
www.univ-lyon fr
Partners:
Prof. Roberto Manservigi

Universita Degli Studi Di Ferrara
Ferrara, Italy
Dr Cornel Fraefel
Zurich, Switzerland
Prof. Thomas Brocker
Ludwig-Maximilians-Universitaet-Muenchen
Muenchen, Germany
Prof. Juan Arbiza

Universidad De La Republica
Montevideo, Uruguay
Dr Jose Paulo Gagliardi Leite
Fundaao Oswaldo Cruz
Rio De Janeiro, Brazil
Prof. Graciela Almallo De Glikmann
Universidad Nacional De Quilmes
Buenos Aires, Argentina
Prof. Juan Daniel Claus
Universidad Nacional Del Litoral
Santa Fe, Argentina
NID-Diarrhoea
127
SUPASALVAC
Salmonella-Free Broilers
by Live Vaccine-Induced
Innate Resistance
to Colonisation
and Invasion and Novel
Methods to Eliminate
Vaccine and Field Strains
Project number: FOOD-CT-2004-505523

Duration: 42 months
Type: STREP
BACKGROUND
The European poultry industry urgently needs a costeffective way of dealing with salmonella in broilers (young
chickens) in order to produce quality-assured, pathogenfree meat at a competitive price. The immune system
of broilers is insufficiently developed when they are
slaughtered (before six weeks) and, as a consequence,
they frequently succumb to infection by pathogenic
salmonella. Strategies are required for the biological
control of the food borne infection in broilers, including
further investigation of promising designer vaccines for
newly hatched chicks.
The results of the SUPASALVAC are expected to pave the

way to producing a highly effective live vaccine designed
for young chicks (based on the best inhibiting strains) with
the genes to promote chick immunity.
AIMS
This project aims to use biotechnology to enhance the
effects of live salmonella vaccines. The activities include
the following:
testing strains of salmonella to see which are best
at inhibiting colonisation by similar strains;
discovering which genes are involved in inhibition;
identifying the genes that draw chick immune cells
to the gut in response to the live vaccine;
identifying the role of intestinal defensin peptides in
controlling colonisation.
The project will also investigate other methods of preventing
colonisation of chick intestines by salmonella, exploring
dietary additives or methods of inhibiting bacterial genes
active during colonisation. Furthermore, bacteria-killing
viruses (known as bacteriophages) will be used to target
particular bacteria. The project is developing phages to
destroy salmonella, both in broilers and in carcasses.
128
Acronym: SUPASALVAC
NID-Diarrhoea
Dr Paul Barrow
Institute for Animal Health
Compton Laboratory
Newbury
Berkshire RG20 7NN
England, UK
Tel: +44-1 63 55 78 411
Dr V Allen
University of Bristol
Bristol, England
UK
Dr M Schellekens
EBI BV
Den Haag, Netherlands
Partners:
Prof. R Ducatelle
Universiteit Gent
Gent, Belgium
Dr U Methner
Federal Research Center for Virus Diseases of Animals
Tbingen, Germany
Dr I Rychlik
Veterinary Research Institute
Brno, Czech Republic
Prof. B Nagy
Veterinary Medical Research Institute
Budapest, Hungary
Dr I Schroder
Lohmann Animal Health
Cuxhaven, Germany
Dr A C Lalmanach
Institut National de la Recherche Agronomique
Paris, France
Dr J Wagenaar
Institut voor Dierhouderij en Diergezondheid
NID-Diarrhoea
129
TRYPADVAC2
Acronym: TRYPADVAC2
Development of an
Anti-Disease Vaccine
and Diagnostic Tests for
African Trypanosomosis

Duration: 36 months
Type: STREP
Project website: www.trypadvac2.eventos.usb.ve/
BACKGROUND
Trypanosomosis, or African sleeping sickness, is a disease
that affects both humans and livestock. Today nearly a third
of Africa is affected by Trypanosomosis which is caused by a
parasite transmitted by the bite of the tsetse fly. The disease
is having a detrimental effect on the development of African
rural communities as it restricts the keeping of farm animals
which affects supplies of meat and milk and also limits the
development of mixed arable and livestock farming.
Previous studies of trypanosome infections have focused
on congopain, an immunosuppressive cysteine protease
(CP) of Trypanosoma congolense. As the effects of
immunisation with congopain are limited, association with
other antigens is required.
Recent developments in the field of proteomics and
progress in the genome mapping of trypanosomes have
provided tools for the study of new pathogenic pathways.
In order to improve diagnosis of the disease, procedures
for antibody detection will be developed and/or validated.
They are based on recombinant technology, which
circumvent problems associated with the current use of
parasite extracts. Recombinant and synthetic peptides
from CPs and heat shock proteins, both previously
identified as major antigens, as well as newly described
molecules, will be assessed for their diagnostic potential.
Techniques for detection of parasite antigens in the host
tissues will be re-examined using recently developed
monoclonal antibodies.
AIMS
The aim of the project is to contribute to the eradication
of Trypanosomosis in humans and livestock through
limitation of trypanosome-associated pathology and
accurate diagnostics of trypanosome infections. It is also
proposed to develop immunisation strategies against
pathogenic factors of trypanosomes.
The current proposals will include screening and
characterisation of other pathogenic molecules,
130
NID-Trypanosome
especially those responsible for anaemia. A number of

other trypanosome proteases - CPs, serine and metalloproteases - require characterisation as to their biological
roles in the parasite and the host. Trypanosomes
also contain protease inhibitors, some of which have
immunomodulatory effects. They may thus be manipulated,
directly or in association with their partner enzymes, to
modulate the disease.

The expected result is a vaccine against Trypanosomosis.
Dr Alain Boulange
Centre de Cooperation International

en Recherche Agronomique
pour le Developpement
42 Rue Scheffer
Paris, France
Tel: +27-3 32 60 61 33
Partners:
Prof. J Mottram
Wellcome Centre for Molecular Parasitology
Glasgow, Scotland
UK
Prof. G Lubega
University of Makerere
Kampala, Uganda
Dr L Neves
University of Eduardo Mondlane

Maputo, Mozambique
Dr P Jacquier
Diamed AG
Cressier-sur-Morat, Switzerland
Prof. V Rosario
Institute of Hygiene and Tropical Medicine
Lisbon, Portugal
Prof. M Gonzatti
Simon Bolivar University

Caracas, Venezuela
Prof. P Buscher
Prince Leopold Institute of Tropical Medicine
Antwerp, Belgium
Prof. T Coetzer
University of Kwazulu-Natal
Westville, South Africa
Prof. S Magez
Flanders University Institute of Biology
Ghent, Belgium
Prof. T Baltz
Paris, France
Dr S Thevenon
Centre International de Recherche
Developpement sur lElevage en Zone Subhumide
Bobo Dioulasso, Burkina Faso
NID-Trypanosome
131
CANCERIMMUNOTHERAPY
Acronym: CANCERIMMUNOTHERAPY
Project number: LSHC-CT-2006-518234
Cancer Immunology
and Immunotherapy

Duration: 48 months
Type: IP
Project website: www.cancerimmunotherapy.eu/
BACKGROUND
Cancer is a major life-threatening disease and the second
greatest cause of mortality in Europe after cardiovascular
diseases. Classical cancer treatment still relies on surgery,
chemotherapy and radiotherapy. Despite clear progress in
some cancer types, cancer therapy in general often fails
to prevent progression to metastatic disease. In addition,
these approaches are very toxic in themselves, imposing
a heavy burden of side effects on the patient. There is
clearly a need for new therapeutic approaches that would
be more efficient and less toxic.
AIMS
The first part of the project consists of vaccination clinical
trials for the comparison of various vaccines, such as
peptides and RNA, with different types of immunological
adjuvants and dendritic cells. Safety and clinical efficacy
are the primary endpoints of these trials. A huge effort is
being made to monitor the anti-vaccine T cell responses,
as examining the correlation between immunological
and clinical responses to the vaccines is crucial to
understanding which factor(s) limit tumour regression. A
second part of the project, tightly connected to the clinical
trials since it uses biological material from the vaccinated
patients, consists of optimising tumour vaccines and
combating immune evasion.
Prospective mechanisms of tumour escape will be analysed and correlated with the clinical results. Improved
modalities of vaccination will be tested and new target
antigens will be identified. All these results will help the
project partners to design improved vaccines. Finally, considering the complexity of mechanisms that may lead to
or prevent tumour regression in vaccinated patients, the
project proposes exploring more fundamental aspects of
the anti-tumour immune response. This includes the crosspresentation of tumour antigens by dendritic cells, recruitment of cells of the innate immune system, involvement of
suppressor T cells, and development of murine models of
inducible tumours. If new concepts emerge from this work,
they will also help in the design of better vaccines.
132
Non-inf-cancer
The preliminary observation that vaccination with tumour

antigens can be associated with tumour regressions, and
in a few cases with sustained remissions, is encouraging,
as it indicates that the vaccines tested so far have an
anti-tumoural activity. Considering that vaccine-induced
immune responses and tumour regressions seem to be
correlated, and that the immune responses that have
been detected so far appear to be quantitatively weak,
it is reasonable to hypothesise that vaccines with a
greater immunogenicity, such as those the partners are
investigating, will also have a greater clinical efficacy.
The project will build a close interaction between the
research laboratory and the clinic, as this will allow new
ideas to emerge from observations made in either of these
two fields, and to be rapidly integrated into new projects.

The project hopes to develop a therapeutic cancer vaccine
with defined tumour antigens that will provide a clinical
benefit in at least 40% of patients. This 40% threshold
of vaccinated patients showing an objective tumour
response, in the absence of unacceptable toxicity, would
definitely qualify immunotherapy as a standard cancer
treatment. Further improvements could come from refining
the vaccinations, and from combining tumour vaccines
with other modalities of cancer treatment.
Thierry Boon
de Duve Institute
Brussels, Belgium
Partners:
Hans-Georg Rammensee
Eberhard-Karls-Universitt Tbingen
Tbingen, Germany
Sebastian Amigorena
Institut Curie
Paris, France
Marc Bonneville
Institut Nationale de la Sant
et de la Recherche Mdicale
Paris, France
Pedro Romero
Ludwig Institute for Cancer Research
Epalinges, Switzerland
Cornelis Melief
Leiden, Netherlands
Chiara Castelli
Fondazione Istituto Nazionale Tumori
Milan, Italy
Gerold Schuler
Friedrich Alexander Universitt Erlangen-Nrnberg
Erlangen, Germany
Thomas Wlfel
Johannes Gutenberg-Universitt Mainz
Mainz, Germany
Eric Tartour
Universit Ren Descartes
Paris, France
Vincenzo Cerundolo
The Chancellor, Masters and Scholars
of the University of Oxford
Oxford, England
UK
Muriel Moser
Brussels, Belgium
Alexander Eggermont
Kris Thielemans
Vrije Universiteit Brussel
Brussels, Belgium
Carl Figdor
Stichting Katholieke Universiteit
Hlne Sicard
Innate Pharma SA
Marseille, France
Federico Garrido
Fundacion Virgen de las Nieves
Granada, Spain
Vincenzo Russo
Fondazione Centro San Raffaele del Monte Tabor
Milan, Italy
Gnter Hmmerling
Deutsches Krebsforschungszentrum
Heidelberg, Germany
Brigitte Dreno
Centre Hspitalier Universitaire de Nantes
Nantes, France
Ulrich Keilholz
Charite Universitatsmedizin Berlin
Berlin, Germany
Jochen Probst
CureVac - the RNA people
Tbingen, Germany
Non-inf-cancer
133
DENDRITOPHAGES
Acronym: DENDRITOPHAGES
Therapeutic Cancer
Vaccines

Duration: 36 months
Type: STREP
Starting date: 1 April 2004
Project website: www.idm-biotech.com/
BACKGROUND
The ultimate goal of anticancer therapeutic vaccines is to

prevent metastasis development and tumour progression,
as well as to provide long-term protection. Previous
studies have shown no side effects associated with this
type of dendritic autologous cellular drug, and immune
and clinical responses were achieved in some patients
who were resistant to conventional therapies.
Results showed an immune response following

vaccination, plus signs of clinical responses in some of
the patients. One patient showed complete regression
of metastases four months after last vaccination, and
another one showed stabilisation of the disease. The
project team compared several technologies for obtaining
DCs and chose to develop the most appropriate. Initial
clinical results were confirmed via a randomised clinical
study conducted in malignant melanoma stage 4 patients,
immunised with DCs pulsed ex vivo with three melanoma
cell lines lysates. Of the 49 patients, 14 initiated T cell
immune response against the antigens presented and 10
patients had the disease stabilised; most of these immune
responses and stabilisations were in the group of patients
having received 6 vaccinations. Studies are continuing in
colorectal and prostate cancer.
AIMS
The project aimed to demonstrate the immune and clinical
efficacy, reproducibility and feasibility of anticancer cell
vaccine by sequential steps: (i) the best dendritic cell (DC)
vaccination strategy via preclinical studies was selected;
(ii) the immune response was monitored in correlation to
the clinical response after identifying the most relevant
immuno-monitoring techniques, demonstrating the
immunological efficacy of DC immunotherapy in prostate
cancer, which was performed after loading ex vivo DCs
with proteic antigen; (iii) a clinical trial was carried out
to evaluate the cell drug on patients with progressing
prostate cancer. The patients blood monocytes were
transformed into effector monocyte-derived DCs, which
fight the disease. The therapeutic cell drug comprised
DCs loaded with cancer-specific antigens, activating the
patients immune system after re-injection.
134
Non-inf-cancer
Jacques Bartholeyns
IDM SA Immuno-Designed Molecules

Paris, France
Tel: +33-1 40 09 04 11
Partners:
Andreas Mackensen
Regensburg, Germany
Miles Prince
Centre for Blood Cell Therapies
Victoria, Australia
Reinhard Glueck
Universit di Catania
Catania, Italy
Thomas Felzmann
Childrens Cancer Research Institute
Vienna, Austria
Filippo Belardelli
Rome, Italy
Non-inf-cancer
135
LCVAC
Acronym: LCVAC
New Vaccination
Therapies for
Lung Cancer

Duration: 24 months
Type: Co-operative Research Projects
Starting date: October 2004
Project website: www.lcvac.org/
BACKGROUND
Lung cancer is the leading cause of cancer related mortality

worldwide. In contrast to many other types of cancer,
no significant improvements in treatment modalities of
lung cancer have been achieved in the last decade. The
major obstacles to its successful treatment include late
diagnosis, heterogeneity of the tumors, highly metastatic
behaviour, resistance to chemotherapy, and the failure to
surgically remove all cancer cells.
Within the LCVAC consortium an important progress was

made regarding the discovery and validation of new lung
cancer specific antigens. Using differential expression
studies and proteome analysis, the NCAM-MUM splice
variant was shown to be a SCLC specific antigen and
expression of the cytokeratin (CK) panel CK6/CK16 was
found to be specific for the squamous cell carcinoma
subtype of NSCLC. Both NCAM MUM and CK6/CK16 are
promising markers to be used for lung cancer diagnosis
and therapeutics. For NCAM MUM recombinant protein
production procedures as well as QA/QC technologies
evaluating the immunogenic potential have been
developed within the scope of this project. NCAM
MUM was shown to be immunogenic, inducing a clear
cellular and humoral immune response in Balb/c mice
immunized with the recombinant protein. Vaccination
approaches were optimized and the infiltration of cells at
the inocculum site was described in detail. Based on the
cellular infiltration at the site of injection, alum absorbed
multiple cytokine adjuvant was shown to be the best
practice for recombinant protein immunisations. DNA
immunization alone was shown to induce only a limited
antibody response and no cellular immune response,
whereas boosting with NCAM MUM recombinant protein
induced a significant humoral and a MUM specific cellular
immune response. The major results of this project are
summarized in 3 scientific publications that are currently
prepared for submission in peer-reviewed journals.
Regarding the IPR, two patents are filed. We conclude that
despite the fact that we have not been able to generate
lung cancer cell lines for the development of an allogenic
cellular lung cancer vaccine, we made important progress
in the discovery and validation of new lung cancer specific
antigens that are very promising for lung cancer diagnosis
and treatment.
A vaccine is essentially a form of purified antigen or

mixture of antigens, together with immune-stimulating
agents (adjuvants), administered to induce an effective
immune response. Unfortunately, effective antigens
specific to lung cancer cells are currently unknown. Also,
lung cancers can be very heterogeneous and contain
variations in lung cancer cell types increasing the difficulty
of developing effective vaccines. The challenge is to find
specific antigens,vaccine formulations and vaccination
approaches in order to stimulate an effective immune
response against the different lung cancer types.
AIMS
LCVACs aims were:
to identify and characterise novel lung cancer
specific antigens using proteome analysis;
to develop an effective and safe vaccination
protocol for antigens and tumor cells;
to characterise and generate human lung cancer
cell lines to be used for an allogeneic cellular
cancer vaccine.
136
Non-inf-cancer
Ren Vleugels
MUbio Products B.V.

Oxfordlaan 70
6229 EV Maastricht, Netherlands
Tel: +31-4 33 88 58 05
Partners:
CIRES cell & immune research services GmbH

Dortmund, D-44227 Germany
Onyvax Ltd
St. Georges Hospital Medical School
London,
UK
Medical Proteome Center
Ruhr-Universitt Bochum
Bochum Germany
Universiteit Maastricht
Department of Molecular Cell Biology
The Netherlands
Non-inf-cancer
137
VITAL
Development of
Optimised Recombinant
Idiotypic Vaccines
for Subset-Specific
Immunotherapy of
B Cell Lymphomas
Acronym: VITAL
Duration: 36 months
Type: STREP
Project website: www.cro.sanita.fvg.it/progetti/
vital/index.htm
BACKGROUND
While therapeutic vaccines targeting B cell non-Hodgkin

lymphoma (NHL) idiotype (Id) are proving their strength
against these malignancies, their extensive use is impeded
by the fact that they are patient-specific. This results in
their complex and pricey individualised production. This
project is using the molecular features of Id proteins of
distinct B cell lymphomas/leukaemias to develop premade, recombinant Id proteins to vaccinate subgroups
of lympho-proliferative disorders expressing molecularly
correlated idiotypes.
It is expected that novel diagnostic and therapeutic

tools will become available on both the European and
international markets.
AIMS
A database is being built of Id sequences expressed by
various B-NHL so as to identify subgroups of tumours
expressing molecularly correlated Id proteins. VITAL will
also do the following:
characterise the selected Id proteins for their
immunogenicity and for the ability to induce crossreactive immune responses against related Id
proteins;
identify B and T cell epitopes;
develop dedicated assays for immunomonitoring;
produce optimised versions of selected Id vaccines
(by using new strategies and validated in animal
models);
assess and validate new adjuvants and delivery
systems for improved Id vaccine formulations and
administration;
generate and filter, based on GMP standards,
the most promising Id proteins, which will then be
included in new vaccine formulations for crossreactive immunotherapy trials;
perform preclinical characterisation of the
immunogenicity of selected natural Id proteins that
can induce immune responses against lymphoma
cells expressing molecularly correlated Id proteins.
138
Non-inf-cancer
Riccardo Dolcetti
Centro di Riferimento Oncologico IRCCS

National Cancer Institute
Aviano, Italy
Tel: +39-0 43 46 59 670
Partners:
Bjarne Bogen
University of Oslo
and Rikshospitalet University Hospital
Oslo, Norway
Maria Masucci
Stockholm, Sweden
Antonio Rosato
University of Padova
Padova, Italy
Hans Petrus Maria Langedijk

Pepscan Systems BV
Nikolai Schwabe
ProImmune Limited
Oxford, England
UK
Maria Luisa Nolli
Areta International S.r.l.
Gerenzano (Varese), Italy
Non-inf-cancer
139
MimoVax
Acronym: MimoVax
Alzheimers DiseaseTreatment Targeting

Truncated ASS40/42 by
Active Immunisation

EC contribution: 2.4 M
Duration: 36 months
Type: STREP
Project website: www.mimovax.eu
BACKGROUND
There are 12 million cases of Alzheimers disease
worldwide and 3.5 million people in Europe are afflicted
with it. It is believed that these figures will double in
the next 20 years as the European population ages.
Alzheimers mostly affects people over 65 years of age
and it is the most common form of dementia. There is
currently no cure for the progressive neuro degeneration
it causes. More research is urgently needed into its
cause both for social and economic reasons. This project
is focusing on the use of immune reactions to fight
Alzheimers, which is caused by deposits of amyloidbeta () peptides which form into clumps (known as
plaques). They develop when parts of a human protein
detach from the cell membrane of nerve cells and stick
together. The project is focusing on developing a vaccine
that breaks down these cell clumps.
AIMS
The aim of MimoVax is to find a vaccine that will cure
Alzheimers. To do this the following objectives will
be carried out:
novel monoclonal antibodies directed against neoepitopes on N-terminally truncated derivatives of
A will be generated and their specificities will be
evaluated;
mimotope peptides will be identified by screening
peptide libraries followed by testing their suitability
by assessing their in vivo immunogenicity in mice;
mimotope-based vaccines will be formulated
and evaluated for efficacy in animal models of
Alzheimers;
in vivo imaging systems will be set up to analyse
anti-A antibody distribution and turnover in mice
as well as effects of the novel Alzheimers vaccine
on plaque deposition in living transgenic animals;
SOPs for manufacturing GMP material will be
determined;
vaccine conjugate formulation for subsequent
analysis of toxicity and for the phase I clinical trial
140
Non-Inf-Alzheimer
will be defined based on the experience from in vivo

data obtained during the project;
analysis of toxicity will be performed in mice
according to standard toxicology protocols for
vaccines to exclude detrimental side effects of the
newly developed vaccines;
a clinical phase I will be performed to analyse
safety of the newly developed Alzheimers vaccine
in human patients.

The project expects to develop a safe Alzheimers vaccine
which can prevent or reverse neuro degeneration.
Dr Frank Mattner
AFFiRiS GmbH
Campus Vienna Biocenter 2
Viehmarktgasse 2A
Vienna, Austria
Tel: +43-1 79 81 57 51 5
Partners:
Manfred Windisch
JSW
Graz, Austria
Antn Alvarez
EuroEspes
Coruna, Spain
Fritz Andreae
piCHEM
Graz, Austria
Richard Dodel
Philipps University Marburg
Marburg, Germany
Alexander Drzezga
Technical University Munich
Munich, Germany
Iris Grnert
Biolution
Vienna, Austria
Non-Inf-Alzheimer
141
Clinical Research
and capacity Building
Introduction
CLINICAL RESEARCH AND

CAPACITY BUILDING
Many factors account for the revived global interest in

vaccines including economic reasons and new scientific
breakthroughs, but maybe the most important aspect is an
increased realisation of public health potential. It makes
sense to use vaccines to quell epidemics and pandemics,
as mass vaccination is more tolerable and more costefficient than long-term care for patients with infectious
diseases. Vaccination can thus contribute enormously to
public health if implemented efficiently at the individual
level. The actual implementation of new vaccines and
improved use of existing vaccines is therefore a critical
aspect to exploit vaccines maximally. This also includes
training of researchers and health personnel in better
understanding of vaccines and vaccinology.
The largest single initiative funded in health research in
FP6 was the European and Developing Countries Clinical
Trials Partnership (EDCTP). The EDCTP is dedicated to
support capacity building and performance of phase II and
III clinical trials in Africa for new treatments and vaccines
against HIV/AIDS, malaria and tuberculosis. The EDCTP
was established under article 169 of the European Treaty
and upon a decision of the European Parliament and
Council in June 2003. The EC has allocated EUR 200
million to the EDCTP, which was established in autumn
2003 as a separate legal entity in The Hague in the
Netherlands. It aims is to integrate European scientists
with sub-Saharan African countries in order to build clinical
research capacity and to develop new treatments and
vaccines against the three big infectious diseases. While
the EDCTP will undertake a wide range of activities, a
significant part will be directly linked to supporting clinical
trials for new vaccine candidates or to building clinical
capacity in Africa for future vaccine research.
The other major activity in clinical vaccine research is a
better integration of clinical vaccine research in Europe in
the HIV/AIDS field. The aim of the EUROPRISE network
of excellence is to better synergise European research on
new preventive technologies for HIV/AIDS, including both
microbicides and vaccine research. The EUROPRISE
network includes about 15 European research projects
funded by both the European Commission and the Gates
144
Foundation, representing more than 132 institutions from

22 countries.
Another NoE, DC-THERA, is focused on the clinical
application of vaccines based on dendritic cells. This
network will integrate the activities of 26 groups of
scientists, clinicians and SMEs into an ambitious Joint
Activity Programme to translate genomic, proteomic and
bioinformatic information into useful endpoints for clinical
trials of DC-based therapies for cancer and HIV.
Besides the above projects, this area also comprises a
number of other activities which focus on networking of
activities, harmonization of clinical activities or human
capacity building through training of scientists. Although
many of these activities have a relatively small budget, they
have an important role in filling the gaps in many research
activities or in building bridges in the scientific community.
1.
2.
3.
4.
5.
6.
7.
8.
9.
DC THERA. Clinical trials on dentritic

cell research for cancer/HIV
INCO PAHPV. Clinical trials on HPV
(Human Papilloma Virus)
INCO COINFECT. Clinical trials on
malaria control
ADVAC-EC. Clinical trials on
Communicable Diseases Linked to
Poverty
NEUTNET. Clinical trials on
standardisation of HIV neutralisation
assays to be used in vaccine research
EURHAVAC. Clinical trials in malaria
vaccine development
REBAVAC. Clinical trials in developing
vaccines to control antibiotic resistant
bacteria
EUROPRISE. Clinical trials in European
vaccines and microbicides enterprise
EDCTP capacity building and clinical
trials
Fig. 4: Vaccines clinical trials information

145
EDCTP
Acronym: EDCTP
European and
Developing Countries
Clinical Trials
Partnership
Project number: F169-CT-2003-980429

EC contribution: 400 million
Duration: 84 months
Type: Article 169
Project website: www.edctp.org
BACKGROUND
Disease prevention in Africa is a top priority, not only in
order to help prevent millions of unnecessary deaths,
but also to begin to free the continent from its perpetual
disease-poverty-disease cycle, so it can begin to grow
economically. The principal diseases devastating Africa
are HIV/AIDS (human immunodeficiency virus/acquired
immune deficiency syndrome), malaria and tuberculosis
(TB), which are currently killing about 5 million people
every year. About 2 million of these die from HIV/AIDS,
for which there is as yet no cure. AIDS also forms a
deadly partnership with TB, which is the leading cause
of mortality in people who are HIV positive. Malaria kills
about 1 million people in Africa every year and 500 million
are infected annually.
These diseases put a huge economic burden on African
families. People on very low wages incur huge debts
and use up to a quarter of their annual income to pay for
treatment for sick relations. If they are unable to save,
they can never escape the poverty-disease trap. The high
economic toll of the main diseases is also contributing
to a decline in per capita income in many sub-Saharan
African countries. When large numbers of the population
are unable to continue working because of severe illness,
harvests are not gathered, factories are less productive
and children are put to work to replace sick adults, again
perpetuating the poverty cycle.
Reducing the disease burden in Africa will take years of
dedicated hard work and cooperation between European
and African scientists and medical specialists. Proper
organisation is also of key importance. Malaria and TB are
both preventable and curable, but need long-term courses
of treatment that must be followed strictly. However, this
procedure is not always implemented and many patients do
not complete their designated treatments. For there to be a
serious reduction in curable diseases such as malaria and
TB, health centres must be established with fully trained
staff who keep registers of patients receiving treatment.
If the disease burden is to be lightened in Africa, longterm and coordinated programmes of action must be
146
undertaken. To this effect, the EC Research Directorate

General has set up a clinical trials programme funded
under the Sixth Framework Programme, at EUR 400
million over 5 years. Experts from 14 EU countries plus
Switzerland and Norway are working alongside African
scientists and medical experts to launch the European
and Developing Countries Clinical Trials Partnership
(EDCTP), to help facilitate and develop clinical trials for
new drugs and vaccines against HIV/AIDS, malaria and
TB. The EC is taking an overarching role in the project,
coordinating and bringing together expertise from all the
participating countries.
AIMS
The Commission has funded research on HIV/AIDS, TB
and malaria for many years. Over EUR 100 million was
spent on research under the Fifth Framework Programme,
for example, but now is the time for a more coordinated
and integrated approach. Increasing the health of the
populations of AIDS-stricken countries, thereby enabling
them to break out of the poverty-disease cycle, and
consequently creating more robust economic and social
conditions are the overall aims of the project. These will
be developed through networking and coordination of both
European and African programmes and activities carried
out in developing countries.
This is truly a joint programme, with European and African
experts and institutes working together. African scientists
and doctors are on the programmes steering committee
and will take a vital part in the process, from the opening
phases until the clinical trials stage. The drugs to be tested
in the clinical trials will be selected taking into account the
needs and the financial means of the recipients in terms of
ease of use and affordability, and trials will be carried out
in full accordance with ethical best practice.
Pharmaceutical companies provide over 60% of drugs
used in developing countries, and many drug and vaccine
candidates originate from private laboratories. However,
a longstanding problem involving health programmes
in developing countries is that it is not feasible for
pharmaceutical companies to commit themselves fully to
developing drugs and vaccines for countries that may not

be able to pay for them. The ECs intention is to solve
this problem by using this programme to bridge the gap
between the needs of developing countries and the
pharmaceutical industrys need to make a profit.
Coordinator:
Prof. Charles Mgone
Executive Director EDCTP

EUROPEAN AND DEVELOPING COUNTRIES
CLINICAL TRIALS PARTNERSHIP
P.O. Box 93015
NL-2509 AA THE HAGUE
The most important results of the programme will be

the establishment of strong roots for future long-term
cooperation between researchers and coordination of
research projects and the development of exchange
courses between European and African institutes and
universities. The pooling of resources such as funding
agencies, expertise and academic institutions will lead to
alliances between European and African partners that will
promote joint activities in training, research and capacity
strengthening, leading to joint calls and policies.
[email protected]
It is hoped that the high visibility of the programme will

help to secure support from scientific, clinical and political
figures in African countries. This is vitally important in
order to develop long-term local strategies to deal with
disease and address the needs of both the people and
the local healthcare systems. The programme will also
help to establish a network of reference laboratories in
Africa and to set up the training of health centre staff,
who can carry out basic medical procedures. In terms of
developing clinical trials, a long-term programme such as
EDCTP will help to strengthen the regulatory environment
for setting up clinical trials, improve the infrastructure for
trial sites and strengthen human resources in trial sites
and institutes.
Putting in place a solid information management structure
will also be an important and long-term result of the
programme. Resolving administrative issues, providing
scientific support, facilitating external representation and
communications, ensuring compliance with contractual
obligations, supporting the setting up of clinical trials
registries and developing tools for dissemination of
knowledge are all vital components for building up a
strong infrastructure for future projects.
Capacity building and site development

for the conduct of phase III trials of TB vaccines
Capacity building in preparation for the conduct
of preventive HIV vaccine trials
and phase III trials of TB vaccines
147
EUROPRISE
Acronym: EUROPRISE
European Vaccines and

Microbicides Enterprise

Duration: 60 months
Type: NoE
Project website: www.altaweb.it/europrise/
BACKGROUND
The successful development of preventative strategies
against HIV-1 infection (microbicides, vaccines or their
combined effects) would provide a pivotal turning point
in global efforts to combat the pandemic spread of
AIDS, with an impact of incalculable value on societal
problems associated with this disease. The principal
aim of this project is to bring together EU scientists
from the microbicide and vaccine fields to embrace
a coordinated approach to HIV-1 infection prevention
research.
Vaccines delivering non-replicating antigens mostly
fail to induce sufficient mucosal responses and
immunological memory to provide protection against
high viral challenge. In contrast, while it may be
technically easier to develop microbicides that prevent
transmission when applied before intercourse, their
duration of protection is likely to be short-lived and
their efficacy will be critically dependent upon user
compliance. To date, both fields have been slow to work
together in the development of products that provide
multiple levels of protection.
This network is focusing on the premise that
microbicides and vaccines targeting multiple stages
of mucosal transmission will have the best chance
of success. Indeed, there are many reasons why the
two fields should collaborate in developing effective
strategies to prevent mucosal vaginal or rectal
transmission, including the facts that approximately 80
% of new HIV infections are now heterosexual, and the
main entry of infection is across the vaginal or rectal
mucosa. Topically applied products are likely to have
a high level of acceptance, and importantly, their use
would be female-initiated. This is an important factor
for women who have no means to protect themselves
if their partners do not use condoms. Also, effective
microbicides are likely to become available before
effective vaccine candidates. Thus it is likely that in the
near future all vaccine efficacy trials will be carried out
in an environment where there is widespread use of
148
vaginal microbicides. Consequently, it will be important

to understand the interaction, and the potential interface
of these different prevention technologies.
AIMS
The project has the following aims:
standardisation and harmonisation of research
tools;
identification of new anti-HIV infection/AIDS vaccine
and microbicide candidates and combinations to
prevent HIV infection/AIDS;
establishment of a clinical development pathway
for vaccines and microbicides within a European
framework;
provision of scientific training in microbicide and
vaccine development;
facilitating access to information relevant to HIV-1
microbicides and vaccines;
provision of a single focus for European HIV-1
microbicide and vaccine research.

The expected results are set out below:
standardisation and harmonisation of research
tools;
the development of a portfolio of existing and
new prevention candidates;
facilitating basic HIV/AIDS research in into
clinical trials;
the increased integration of European research
in the fields of HIV-1 vaccine and microbicide
research;
the development of an Internet resource.
Robin Shattock

London, England
UK
Tel: +44-2 08 72 55 855
Scientific Coordinator:
Hans Wigzell
Stockholm, Sweden
Co-Coordinator for Vaccines:
Rino Rappuoli
Novartis Vaccines and Diagnostics srl
Siena, Italy
149
Partners:
M Cranage; D Lewis
St Georges Hospital University of London
London, England
UK
H Wigzell; Dr B Wahren; Dr F Chiodi; A L Spetz
Stockholm, Sweden
H Holmes; N Almond; R Stebbingse

National Biological Standards Board
Potters Bar, England
UK
D Medaglini; G Pozzi
Universita di Siena
Siena, Italy
R Weiss
University College London
London, England
UK
F Gotch; S Patterson
Imperial College of Science, Technology & Medicine
London, England
UK
A Tagliabue
ALTA
Siena, Italy
V Jespers
Prince Leopold Institute for Tropical Medicine
Antwerp, Belgium
G Voss
GlaxoSmith Kline
Rixensart, Belgium
S McCormack; A Nunn; J Bakobaki

Medical Research Council
London, England
UK
R Rappuoli; Dr S Barnett; G Del Giudice

Novartis Vaccines and Diagnostics
Siena, Italy
H Katinger; G Steiglere
Polymun
Vienna, Austria
150
K Uberla
Ruhr Universitat
Bochum, Germany
G Scarlatti; G Poli; P Lusso

Centro San Raffaele
Milan, Italy
C Kelly; T Lehner; L Klavinskis

Kings College London
London, England
UK
R Le Grand
Commissariat a lEnergie Atomique
Paris, France
G Scalae
Universita di Napoli
Naples, Italy
B Verrier
Institut National de la Sante et de la Medecine
Paris, France
C Lacey
University of York
York, England
UK
Q Sattentau
Oxford, England
UK
P La Colla
Universit di Cagliari
Cagliari, Italy
Deutsches Primatenzentrum GmbH
Goettingen, Germany
Feny
Lunds Universitet
Lund, Sweden
F Tangy
Institut Pasteur
Paris, France
D Zipeto
Universit di Verona
Verona, Italy
S Norley
Robert Koch-Institut
Berlin, Germany
E Karamov
Russian Academy of Medical Science
Moscow, Russia
K Nihlmark
Mabtech AB
Stockholm, Sweden
N Dedes
European AIDS Treatment Group e.V.
Dusseldorf, Germany
C Moog
Universite Louis Pasteur
Strasbourg, France
H Schuitemaker
Sanquin
J Alcami; R Najera
Instituto de Salus Carlos III
Majadahonda, Spain
G Leroux-Roels
Ghent University
Ghent, Belgium
151
DC-THERA
Acronym: DC-THERA
Dendritic Cells for

Novel Immunotherapies

Duration: 60 months
Type: NoE
Project website: www.dc-thera.org
BACKGROUND
Dendritic cells (DC) form part of the immune system and
are found in most body tissues, particularly in the skin and
lining of the gastro-intestinal tract. Their job is to process
and ingest antigen material including foreign bacteria that
invades the body. They control many types of immune
response and consequently there is growing interest in
using DC in HIV/AIDS and cancer research and many other
diseases. Dendritic cell immunobiology has enormous
potential for the development of new immunotherapies for
cancer and infectious disease and this project focuses on
these potentials.
AIMS
The projects aim is to facilitate the translation of genomic,
proteomic and bioinformatic information with knowledge
from molecular cell biology and pre-clinical models towards
clinical trials of DC-based therapies for cancer and HIV. It
will do this by an ambitious joint programme of activities, with
the intention of restructuring the field of immunotherapy.

The network is translating genomic, proteomic and
bioinformatic information, along with knowledge pertaining
to molecular cell biology and preclinical models, into
therapeutic endpoints, namely clinical trials of DC-based
therapies for cancer and HIV.
Jonathan Austyn
Oxford, England
UK
Partners:
Gordon G MacPherson
Oxford, England
UK
152
Vincenzo Cerundolo
Oxford, England, UK
Carl G Figdor/Gosse Adema
Radboud University Medical Centre
Muriel Moser
Universite Libre de Bruxelles
Brussels, Belgium
Anne OGarra
Medical Research Council
London, England
UK
Francesca Granucci
University of Milano-Bicocca
Milan, Italy
Gerold Schuler/Alexander Steinkasserer
Friedrich-Alexander-Universitt Erlangen-Nrnberg
Erlangen, Germany
Robert Coffin
Biovex
Abingdon, England
UK
Catherine De Greef
Brucells
Brussels, Belgium
Ugo DOro
Chiron
Siena, Italy
Andrea Splendiani
Leaf Bioscience
Milan, Italy
Charles Nicolette
Argos Therapeutics
Durham, USA
Philippe Pierre
CNRS-INSERM-Univ Med
Marseille, France
Duccio Cavalieri
University of Florence
Florence, Italy
Maria Pia Protti

Scientific Instituto San Rafaelle
Milan, Italy
Sandra Gessani
Rome, Italy
Alexander Scheffold/Andreas Radbruch/Andreas Thiel

Deutches Rheuma-Forchungszentrum
Berlin, Germany
Nicolas Glaichenhaus
Universit de Nice-Sophia Antipolis
Valbonne, France
Caetano Reis e Sousa

Cancer Research UK
London, England
UK
Rolf Kiessling/Pavel Pisa/Hakan Mellstedt

Stockholm, Sweden
Benedita Rocha
INSERM U591 Institut Necker
Paris, France
Federica Sallusto/Antonio Lanzavechia/Markus Manz/
Mariagrazia Uguccioni
Mark Suter
Zurich, Switzerland
Kris Thielemans
Medical School of the Vrije Universiteit Brussel
Brussels, Belgium
Filippo Petralia
SEKMED
Milan, Italy
Sebastian Amigorena
Institut Curie, Paris, France
Alberto Mantovani
Istituto Clinico Humanitas
Milan, Italy
C J M Melief
Leiden, Netherlands
Hermann Wagner
Technische Universitt Mnchen
Munich, Germany
Laurence Zitvogel
ERM0208 INSERM
Villejuif, France
Paola Ricciardi-Castagnoli
Universit degli Studi di Milano-Bicocca
Milano, Italy
Matthias Mann
Max-Planck-Institut fr Biochemie
Martinsried, Germany
Thierry Boon/Pierre Coulie

University of Louvain
Brussels, Belgium
153
ENACT
European Network
for the Identification
and Validation
of Antigens and
Biomarkers in Cancer
and their Application
in Clinical Cancer
Immunotherapy

Duration: 36 months
Type: STREP
Project website: www.enactcancerresearch.org/
BACKGROUND
Cancer remains a major health problem with enormous

economic, physical and emotional costs to citizens and
the state. Latest statistics show that more than one in three
people will develop some form of cancer in their lifetime.
Along with cardiovascular disease it is the biggest source
of health care costs and suffering in Europe.
ENACTs results are set out below:
Results from recent immunotherapy trials suggest that

inducing tumour-specific T cell responses to tumour
antigens, can cause the regression of tumours or the
stabilisation of the disease in some patients. However,
the mechanisms underlying the failure of immunotherapy
to control and destroy residual cancer are not yet fully
understood. Current knowledge of adoptive cancer
immunity suggests that immune tolerance can equate with
lack of response, with possible regulation by CD4+CD25+T
lymphocytes, as well as other regulatory cells. Breaking
tolerance through immunotherapy therefore represents
one possible approach to promote T-cell responses and
tumour regression.
AIMS
This project aimed to identify markers of response and
tumour antigens associated with ovarian, breast and
prostate cancer, as well as melanoma progression and
resistance to immunotherapy. A technological base was
established for vaccine development (not necessarily
restricted to cancer vaccines), and a better understanding
of the basic biological mechanisms underlying antigen
presentation and recognition of tumours by CD8+ and
CD4+ T lymphocytes and NK cells emerged.
154
Acronym: ENACT
identification of markers relating to the outcome of

immunotherapy;
clinical material and cancer cell lines for scientific
investigation;
cellular and humoral immune responses for patients
undergoing immunotherapy;
biomarkers using proteomics and computer-based
algorithms;
immunological, genetic and proteomic biomarkers
as indicators of therapeutic response related to
gender.
Prof. R Rees
Nottingham Trent University School of Science

Clifton Lane
Nottingham NG11 8NS
England, UK
Tel: +44-0 11 58 48 66 56
Partners:
Italo Dodi
Nottingham Trent University
Nottingham, England
UK
Elissaveta Naumova
University Hospital
Sofia, Bulgaria
Graham Pawelec
Abt.Innere Medizin II Zentrum
fr Medizinische Forschung
Tbingen, Germany
Rolf Kiessling
Stockholm, Sweden
Federico Garrido
Hospital Universitario
Granada, Spain
Dirk Schadendorf
University Hospital Mannheim

Mannheim, Germany
Gustav Gaudernack
The Norwegian Radium Hospital
Oslo, Norway
Graham Ball
Loreus Ltd
Nottingham, England
UK
Costas Baxevanis
Hellenic Anticancer Institute
Athens, Greece
Mike Whelan
London, England
UK
Francine Jotereau
INSERM U463
Nantes, France
Piotr Laidler
Jagiellonian University
Krakw, Poland
Aija Line
University of Latvia
Riga, Latvia
155
ADVAC-EC
Advanced Vaccinology
Training for Scientists
from ACC and Developing
Countries: From
Genomics to Vaccination
Strategies for
Communicable Diseases
Linked to Poverty
Project number: LSSP-CT-2004-005106

Duration: 36 months
Type: SSA
Project website: ADVAC.org
BACKGROUND
Spreading knowledge and practice of vaccinology in

developing countries is a priority and with this aim the
Mrieux Foundation and University of Geneva, partners
of the ADVAC-EU project, organised an advanced
vaccinology course for the duration of the project. The
two-week course was held once a year and comprised
top-level lectures followed by interactive discussions and
specific practical exercises in small working groups. Focus
was placed on vaccines against HIV, tuberculosis and
malaria. The course promoted contacts and international
networks development.
The expected result is the advancing of knowledge of

vaccinology in Europe and in developing countries.
Funding from the EC ensured that scientists from

developing countries, associated candidate countries,
Russia, other newly independent states and the western
Balkans benefited from fellowships for travel, housing
and registration.
AIMS
The overall objective of the ADVAC-EU project was
to create a critical mass of people, in Europe and in
developing countries, with a sufficiently broad knowledge
of vaccinology to be able to play a leading role in decisionmaking processes concerning the following:

156
Acronym: ADVAC-EC
preclinical vaccine research (go/no-go);

design and monitoring of clinical trials;
vaccine safety issues;
selection of new and appropriate vaccination
strategies, including economic aspects and
communication.
Paul-Henri Lambert
Foundation Mrieux
Lyon, France
Tel: +41 22 37 95 783/777
Partner:
Claire-Anne Siegrist
CMU Centre of Vaccinology
Geneva, Switzerland
157
NeutNet
Acronym: NeutNet
Standardisation of
HIV Neutralisation
Assays to be Used
in Vaccine Research
and Clinical Trials
Project number: LSSP-CT-2004-012190

Duration: 27 months
Type: SSA
Project website: www.sanraffaele.org
BACKGROUND
It is well established that antibodies play an important
part in protection against viral diseases such as measles
and influenza, but the role of neutralising antibodies in
HIV-1 protection and pathogenesis remains to be further
defined. Production of an antibody response with a broad
neutralising activity against primary isolates of multiple
HIV-1 subtypes continues to be a desired characteristic
for candidate HIV vaccines. To support the evaluation
of phase I, II and III human vaccine trials testing new
HIV immunogens, it is important to standardise as far
as possible and apply high-throughput specific and
reproducible HIV neutralisation assays. Standardised
HIV neutralisation assays make it possible to compare all
vaccine efforts throughout the world.
AIMS
The project primarily aims to coordinate activities
to standardise methods for the measurement of
neutralising antibodies to HIV-1 to be used in vaccine
research and clinical trials. Other aims are:
developing and centralising the necessary reagents
to undertake the study;
preparing a draft protocol and guidelines for the
study;
organising an initial study to compare different
neutralisation methods using a number of wellknown monoclonal antibodies against a panel of
well-characterised viruses;
defining the methods for data analysis and
statistical comparisons of assay results from the
different participants;
organising a subsequent study to compare
polyclonal serologic reagents and defining the best
conditions to determine neutralising activity;
defining the needs of the scientific community
involved in both preventive and candidate materials
for evaluation;
organising a workshop in collaboration with WHO/
UNAIDS to discuss the results of the actions listed
158
above and share the information with a larger body

of researchers in this field.

The expected results of the project include:
collection of reagents and materials for the study;
development of a questionnaire for the collection of
information about reagents and assays;
definition of the statistical significance of the
different methods;
definition of the standards for neutralisation assay;
international workshop on standards for
neutralisation assays
dissemination of SOPs and workshop proceedings.
Gabriella Scarlatti
DIBIT San Raffaele Scientific Institute

Via Olgettina 58
Milan, Italy
Tel: +39-2 26 43 28 21
Vicky Polonis
Henry Jackson Foundation
Rockville, Maryland
USA
Terri Wrin
MonogramBio Inc
San Francisco, California
USA
Eva Maria Fenyo

Lund University
Lund, Sweden
Partners:
Susan Zolla-Pazner
New York University School of Medicine
New York City
USA
Harvey Holmes
Pottersbar, England,
UK
David C Montefiori
Duke University Medical Center
Durham, North Carolina
USA
Christiane Moog
University Louis Pasteur

Strasbourg, France
Saladin Osmanov
World Health Organisation

Geneva, Switzerland
Quentin Sattentau
Oxford, England,
UK
Lynn Morris
National Institute for Communicable Diseases
Johannesburg, South Africa
Ruengpung Sutthent
Mahidol University
Bangkok, Thailand
Vera Bongertz
Oswaldo Cruz Foundation
Rio de Janeiro, Brazil
159
COINFECT
Acronym: COINFECT
Malaria and
Coinfection:
New Insights
for Malaria Control

Duration: 24 months
Type: SSA
Project website: www.coinfect.eu
BACKGROUND
Malaria and helminth infections often occur at the same time

in tropical regions and their interaction can alter the course
of the malaria infection and disease. Helminth infections
alter the immune system affecting responses to third party
antigens.The studies carried out so far seem to agree that
helminth co-infections seem to either exacerbate or curtail
the degree of malarial disease. New studies need to be
carried out to gain in-depth knowledge of the interaction
between these parasites in humans in the context of
controlling malarial parasites and clinical disease.
The results are expected to include:
AIMS
The overall aim of the project is to deliver the information
and tools necessary for researchers in Asian countries to
produce robust data on malaria and helminth coinfection
and their immunological interaction. COINFECT will be
used to transfer knowledge and technology between
European, Malaysian and Indonesian experts in the area
of malarial and helminth coinfection, in order to prepare a
team with the ability to carry out high quality research in
this important area. This will be achieved by:
training in the setting up of specific epidemiological
studies;
developing questionnaires;
training medical staff in clinical assessment;
training in malarial diagnosis quality control;
training in helminth diagnosis quality;
standardised procedures for collection of blood by
finger prick;
demonstration of immunological methods that
measure antibodies and cytokines;
demonstration of molecular biological methods that
measure gene expression by quantitative PCR and
determine genetic polymorphisms.
Pilot study:
The trained personnel will carry out pilot studies to determine
the prevalence of malarial and helminth coinfections and the
immunological interaction between these two infections.
160
trained clinicians and nurses in Indonesia and

Malaysia;
trained researchers with expertise in high quality
diagnosis of malaria and helminth infections using
quantitative PCR;
trained scientific staff to perform antibody
measurements and interpret them;
staff able to perform and interpret cellular and
molecular immunological tests;
scientists with up to date knowledge of genetic
studies and methodologies;
trained scientific staff able to analyse data;
trained scientists who are able to collect accurate
data on malaria and helminth coinfection; consent
forms for study participants;
questionnaires specific for estimating prevalence of
severe malaria in communities;
SOPs for all immunological tests;
database templates for collection of (immuno)
epidemiological data on coinfection;
results of the pilot study.
Prof. Dr Maria Yazdanbakhsh
Laboratory for Parasitology
Albinusdreef 2
Leiden, Netherlands
Tel:+31-7 15 26 50 67
Partners
Prof. Dr Peter G Kremsner

Eberhard Karls University of Tuebingen
Tuebingen, Germany
Dr. Taniawati Supali

University of Indonesia
Jakarta, Indonesia
Prof. Dr Rahmah Noordin
Universiti Sains Malaysia
Penang, Malaysia
161
EURHAVAC
Acronym: EURHAVAC
European Network
for Harmonisation
of Malaria Vaccine
Development

Duration: 24 months
Type: SSA
Project website: www.emvi.org/eurhavac
BACKGROUND
Malaria vaccines require a series of coordinated

steps ranging from basic research and identification
of lead vaccine candidates to evaluation for safety and
immunogenicity in Europe before they can be clinically
tested in Africa for safety, immunogenicity and efficacy.
Before licensure, these vaccines will be tested in large
multicentre trials on thousands of people, as required by
national and EU regulatory authorities. There has been
considerable investment at national and EU level in
malaria basic research, but this has not been matched
by investment in moving experimental vaccines through
manufacturing and clinical testing. Common guidelines on
harmonised preclinical and clinical evaluation and agreed
decision-making criteria are needed to provide a more
rational basis for the development of malaria vaccines.
The project is helping to create an enabling environment

capable of coordinating resources - available in the
European Research Area - into a network proficient in
managing the existing and desired knowledge. Such
knowledge management will provide for the development
of strategice approaches to malaria vaccine development
and evidence-based benchmarking.
This project is sharing information and identifying

and prioritising the most critical scientific, technical
and regulatory questions. It will be the basis for the
implementation of common standards for assessing
research results.
AIMS
the definition and implementation of decisionmaking processes for pharmaceutical development;
the definition and implementation of a clinical
development strategy;
the harmonisation of the evaluation criteria for
malaria vaccines;
the dissemination of knowledge and information
yielded by the three first action plans.
162
Sren Jepsen

5 Artillerivej
Copenhagen, Denmark
Tel: +45 32 68 32 68
163
PAHPV-1
Acronym: PAHPV-1
HPV Pilot Action

Indonesia

Duration: 16 months
Type: SSA
Starting date: 16 April 2004
BACKGROUND
HPV (Human Papilloma Virus) is the most common

sexually transmitted disease. Infection of the uterine
cervix with oncogenic HPV types (e.g. HPV16, 18, 31, 33,
and 45) occurs in 80% of sexually active women, mostly in
developing countries, and large prospective studies show
that acquisition of HPV from male partners is common.
Progressive HPV-related diseases cause 233 000 deaths
worldwide per year.
It is anticipated that the project will generate new

information on the epidemiology of HPV types and infection
rates. The results of the study will enhance the knowledge
of HPV infections in Indonesia, in combination with the
HPV-specific immunological status in healthy women and
patients with cervical HPV-related disorders.
In this pilot action, Leiden University Medical Center and its

counterparts in Indonesia (Jakarta and Bali) ran a clinical
trial programme of 200 women to chart the percentage
at risk for progressive HPV 16 as well as the immune
response to this HPV type. For this purpose, the feasibility
of a simple, low-cost DTH skin test to detect HPV-immune
reactivity was examined. Once the DTH skin test proves
useful for detecting protective immune responses against
HPV16 it will become accessible to other developing
countries and will be helpful in the selection of individuals
in need of specific vaccination.
AIMS
The aims of the project were as follows:
to collect epidemiological data on the incidence
of HPV16 and the immune status against the
virus in preparation for a future HPV vaccination
programme;
to include HPV education and screening in current
STD campaigns in Jakarta and Bali and share
the experiences with HPV researchers in other
developing countries.
164
Project coordinator:
Prof. Dr G G Kenter

Leiden, Netherlands
Tel: +31-7 15 26 33 32
Partners:
Prof. Santoso Cornain

Immunopathology Laboratory
University of Indonesia, Faculty of Medicine
Jakarta, Indonesia
Prof. Surya
Rumah Sakit Sanglah
Denpasar
Bali, Indonesia
165
REBAVAC
Novel Opportunities
to Develop Vaccines
to Control Antibiotic
Resistant Bacteria:
from the Trials Back
to the Laboratory
Acronym: REBAVAC
Project number: LSHM-CT-2006-037163
Duration: 12 months
Type: SSA
Project website: www.altaweb.eu/rebavac
BACKGROUND
Antibiotic resistant bacteria are rapidly spreading

worldwide, making it increasingly difficult to treat
infections in large communities and, therefore, creating
a major public health problem. Vaccination appears to
be the best way to stop the spread and development
of antimicrobial resistant micro-organisms. However,
the analysis of the effects of using conjugated vaccines
against Spn, Haemophilus influenzae b (Hib) and Neisseria
meningitidis (Men) has shown a number of paradoxes
and some interesting aspects that have led to a re-think
about how immunity to polysaccharide is elicited following
vaccination, and how memory is acquired. REBAVAC was
a workshop which discussed the implication of the abovementioned results and the results of ongoing research on
the use and development of vaccines to fight antibiotic
resistant bacteria.
The workshop will help European and international

research and industry move towards more efficient/
efficacious vaccines and vaccination strategies, and find
novel immunisation methods for optimising the use and
formulation of currently available vaccines that can fight
antibiotic resistance.
A careful analysis of the results of past and current

vaccination trials was necessary to design novel vaccines
or vaccination strategies which can be developed as a
main tool to fight antibiotic resistance.
AIMS
At the workshop the worlds most important experts in
vaccinology and immunology met healthcare providers,
industry representatives and public health experts and
discussed the key issues outlined above, including
how to use and improve currently available conjugate
polysaccharide vaccines to fight antibiotic resistant bacteria,
and how better to understand the contribution of innate and
adaptive components of the immune system in eliciting and
boosting immune responses to conjugate vaccines.
166
Aldo Tagliabue
CEO ALTA Srl
Siena, Italy
Tel: +39-0 57 72 43 508
167
Index by acronym
ADVAC-EC.................................................................... 156
FLUVACC........................................................................ 92
AIDS-CoVAC.................................................................. 40
HEPACIVAC.................................................................. 104
AIV VACC DIAGNOSIS................................................ 114
HEVAR......................................................................... 126
Allomicrovac.................................................................. 64
HIVAB............................................................................ 42
AUTO/ALLO CELL-HIV.................................................. 60
HIV VIROSOMES.......................................................... 68
AVIP.............................................................................. 56
ImmunoGrid................................................................... 46
BacAbs........................................................................... 30
ImmunoVacTB................................................................ 90
BOVAC......................................................................... 120
INNOVAC....................................................................... 44
CANCERIMMUNOTHERAPY........................................ 132
Intranasal H5vaccine.................................................... 98
CHIMERIC VACCINES.................................................. 100
LCVAC.......................................................................... 136
COINFECT.................................................................... 160
MALINV......................................................................... 80
CompuVac...................................................................... 28
MICROBEARRAY........................................................... 32
DC-THERA................................................................... 152
MimoVax..................................................................... 140
DC-VACC........................................................................ 36
MuNanoVac................................................................... 26
DEC-VAC........................................................................ 34
MUVAPRED................................................................... 20
DENDRITOPHAGES...................................................... 134
MVACTOR..................................................................... 50
DISSECT....................................................................... 106
Neotim........................................................................... 86
EDCTP.......................................................................... 146
NeutNet....................................................................... 158
EMVDA.......................................................................... 74
NOVADUCK................................................................. 112
ENACT.......................................................................... 154
OMVac......................................................................... 124
EPI-VAC......................................................................... 72
PAHPV-1..................................................................... 164
EPIVAC.......................................................................... 24
PANFLUVAC................................................................... 96
EURHAVAC.................................................................. 162
Pox-gene....................................................................... 62
EUROPRISE................................................................. 148
PRIBOMAL.................................................................... 76
FluVac............................................................................ 94
REBAVAC..................................................................... 166
RMVHIV........................................................................ 58
SARS/FLU VACCINE.................................................... 110
SARSVAC..................................................................... 108
SAVINMUCOPATH...................................................... 122
SCOOTT....................................................................... 116
SME-Malaria................................................................. 78
SUPASALVAC............................................................... 128
TB-VAC.......................................................................... 82
THERAVAC..................................................................... 38
TIP-VAC......................................................................... 70
TRANCHI..................................................................... 118
TRYPADVAC2.............................................................. 130
Universal Vaccine........................................................ 102
Vaccines4TB.................................................................. 88
VaccTIP.......................................................................... 48
VIAV.............................................................................. 66
VITAL........................................................................... 138
Index by coordinator
Austyn, Jonathan
DC-THERA....................................................................................... 152
Bartholeyns, Jacques
SUPASALVAC................................................................................... 128
Goudsmit, Jaap
PRIBOMAL........................................................................................ 76
Hilgers, Luuk A Th
FluVac................................................................................................ 94
DENDRITOPHAGES.......................................................................... 134
Boon, Thierry
CANCERIMMUNOTHERAPY............................................................ 132
Barrow, Paul
Boulange, Alain
TRYPADVAC2.................................................................................. 130
Huet, Jacqueline
MuNanoVac....................................................................................... 26
Jepsen, Soren
EURHAVAC...................................................................................... 162
Kenter, G G
PAHPV-1......................................................................................... 164
Bublot, Michel
Klatzmann, David
Cortese, Riccardo
Koopman, Gerrit
Cutting, Simon M
Lambert, Paul-Henri
Crisanti, Andrea
Leclerc, Claude
Daura, Xavier
Lehner, Thomas
Dolcetti, Riccardo
Leroy, Odile
Enjuanes, Luis
Liljestrom, Peter
Ensoli, Barbara
Ludewig, Burkhard
Epstein, Alberto
Lund, Ole
Ferrantelli, Flavia
Maizels, Rick
Glck, Reinhard
Mattner, Frank
Goovaerts, Danny
McCullough, Kenneth
NOVADUCK..................................................................................... 112
HEPACIVAC...................................................................................... 104
INNOVAC........................................................................................... 44
MICROBEARRAY............................................................................... 32
BacAbs............................................................................................... 30
VITAL............................................................................................... 138
DISSECT........................................................................................... 106
AVIP.................................................................................................. 56
HEVAR............................................................................................. 126
VIAV.................................................................................................. 66
SME-Malaria..................................................................................... 78
AIV VACC DIAGNOSIS.................................................................... 114
CompuVac.......................................................................................... 28
Pox-gene........................................................................................... 62
ADVAC-EC........................................................................................ 156
THERAVAC......................................................................................... 38
Allomicrovac...................................................................................... 64
EMVDA.............................................................................................. 74
VaccTIP.............................................................................................. 48
AIDS-CoVAC...................................................................................... 40
Vaccines4TB...................................................................................... 88
TRANCHI......................................................................................... 118
MimoVax......................................................................................... 140
PANFLUVAC....................................................................................... 96
Meinke, Andreas
OMVac............................................................................................. 124
BOVAC............................................................................................. 120
Mgone, Charles
EDCTP.............................................................................................. 146
Muster, Thomas
SARS/FLU VACCINE........................................................................ 110
OGarra, Anne
DC-VACC............................................................................................ 36
Pizza, Mariagrazia
SARSVAC......................................................................................... 108
Ramne, Anna
Universal Vaccine............................................................................ 102
Rappuoli, Rino
MUVAPRED....................................................................................... 20
Rees, R
Spetz, Anna-Lena
AUTO/ALLO CELL-HIV...................................................................... 60
Stanescu, Ioana
EPIVAC.............................................................................................. 24
Stiegler, Gabriela
HIV VIROSOMES.............................................................................. 68
Sutter, Gerd
MVACTOR......................................................................................... 50
Tagliabue, Aldo
REBAVAC......................................................................................... 166
Taylor, David W
SCOOTT........................................................................................... 116
Thole, Jelle
TB-VAC.............................................................................................. 82
berla, Klaus
ENACT.............................................................................................. 154
DEC-VAC............................................................................................ 34
TIP-VAC............................................................................................. 70
Rnia, Laurent
van der Zeijst, Bernard A M
Rossi, Elda
Vleugels, Ren Marie Paul
Rottenberg, Martin
Voss, Gerald
Scala, Giuseppe
Wolf, Hans
Scarlatti, Gabriella
Yazdanbakhsh, Maria
MALINV............................................................................................. 80
ImmunoGrid....................................................................................... 46
Neotim............................................................................................... 86
EPI-VAC............................................................................................. 72
NeutNet........................................................................................... 158
Seipelt, Joachim
FLUVACC............................................................................................ 92
Intranasal H5vaccine........................................................................ 98
CHIMERIC VACCINES...................................................................... 100
Shattock, Robin
EUROPRISE..................................................................................... 148
Sirard, Jean-Claude
SAVINMUCOPATH.......................................................................... 122
ImmunoVacTB.................................................................................... 90
LCVAC.............................................................................................. 136
RMVHIV............................................................................................ 58
HIVAB................................................................................................ 42
COINFECT........................................................................................ 160
European Commission
Vaccines for Humans Research funded by the European Union
Luxembourg: Office for Official Publications of the European Communities
2008 176 pp. 21.0 x 29.7 cm
ISBN
DOI
978-92-79-09455-2
10.2777/84341
How to obtain EU publications

Our priced publications are available from EU Bookshop (http://bookshop.europa.eu), where you can place an
order with the sales agent of your choice.
The Publications Office has a worldwide network of sales agents. You can obtain their contact details by sending
a fax to (352) 29 29-42758.
KI-81-08-337-EN-C
Europe has a long and successful tradition for vaccine research in both public and private institutions. Two-thirds of
global vaccine R&D is being conducted by European organisations and almost 90% of all vaccine production takes
place in Europe. Europe is therefore well positioned to take on new challenges in vaccine research, and exploit the
immense opportunities that are opening up in this field of science. The European Commissions Sixth Framework
Programme for Research (FP6) has been an important catalyst in this direction and has provided substantial
momentum to further advance the European activities in vaccine research.
This publication compiles the projects on human vaccine research that were initiated during FP6 (2002-2006). Most
of the projects have been funded through the Health theme of FP6, although important contributions came from
the Food theme, the Information Society theme (IST) and from cross-cutting activities on international cooperation
(INCO), and the support activities to small and medium-sized enterprises (COOP). Many of the projects will not
conclude before 2009 or later, but they are already beginning to deliver important results. Taken together they
provide evidence of a vibrant, visionary and ambitious research community, where hundreds of scientists are working
together to discover and develop new vaccines for the world.

Vaccines For Humans

Uploaded by

Copyright:

Available Formats

Vaccines For Humans

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Vaccines For Humans

Uploaded by

Copyright:

Available Formats

VACCINES

Interested in European research?

EUROPE DIRECT is a service to help you find answers

European Communities, 2008

HUMAN VACCINE RESEARCH IN THE EUROPEAN UNION

EUROPEAN VACCINE RESEARCH

Mucosal Vaccines for Poverty-Related Diseases

Development of a Multi-Step Improved Epidermis Specific Vaccine Candidate against HIV/AIDS

Mucosal Nano-Vaccine Candidate for HIV

Assessment of Structural Requirements in Complement-Mediated Bactericidal Events: Towards a Global

Generation of Broadly Cross-Neutralising Antibodies for Innovative Active-Passive

The European Virtual Human Immune System Project

Host Immune Activation-Optimised Vaccinia Virus Vectors for Vaccine Development

Diseases Specific Vaccine Research

DISEASE SPECIFIC VACCINE RESEARCH

AIDS Vaccine Integrated Project

Development of a Novel Therapeutic HIV-1 Vaccine: Horizontal Gene Transfer

A Combined Pox-Virus/Lentiviral Vector System to Treat HIV Infection;

A Combined Microbicidal-Immunising Strategy Against SIV and HIV Infection

Very Innovative AIDS Vaccine

Development of a New Vaccine against HIV: Virosomes Incorporating HIV Proteins

Identification of Novel Epitopes as HIV-1Vaccines Candidates

The European Malaria Vaccine Development Association

A New Approach for Developing a Less Immunosuppressive Vaccine for Tuberculosis

Live Attenuated Replication-Defective Influenza Vaccine

Dose Sparing and Increased Immunogenicity for Vaccination

Efficacious Vaccine Formulation System for Prophylactic Control of Influenza Pandemics

Protective Efficacy of Intranasal del NS1 (H5N1) Influenza Vaccine

100 CHIMERIC VACCINES

Novel Antigen -Adjuvant Vehicle as an Effective Influenza Vaccine

New Preventative and Therapeutic Hepatitis C Vaccines:From Preclinical to Phase I

110 SARS/FLU VACCINE

AIV VACC DIAGNOSIS

Vaccine, Diagnostic Test Development and Immunology Aspects of Avian nfluenza

Development of a Prophylactic Vaccine and Diagnostic Markers to Diagnose

Herpesvirus-based Vaccines against Rotavirus Infections

New Vaccination Therapies for Lung Cancer

Development of Optimised Recombinant Idiotypic Vaccines

Clinical Research and capacity Building

CLINICAL RESEARCH AND CAPACITY BUILDING

European and Developing Countries Clinical Trials Partnership

European Vaccines and Microbicides Enterprise

European Network for Harmonisation of Malaria Vaccine Development

HPV Pilot Action Indonesia

HUMAN VACCINE RESEARCH

The use of vaccines is saving millions of lives every year,

The vast majority of vaccine and vaccinology activities

Vaccine research has seen a remarkable renaissance

scientifically challenging that it may never occur without

Fig. 1: Overview of EC funded human vaccine research in FP6

Developing Countries Clinical Trials Partnership (EDCTP)

Fig. 2: Overview of instruments used for funding vaccine research in FP6

Significant efforts were also made to build partnerships

The European vaccine research in FP6 is pointing

Vaccine research has come a long way in the past 20 years,

The 15 EC funded projects have addressed a wide

Table 1: EC-funded projects in basic vaccinology

Many researchers are contributing to this exploration of

Many infectious diseases are caused by pathogens that