Vaccines

344 KiB

Open AccessArticle

CD137 Enhancement of HPV Positive Head and Neck Squamous Cell Carcinoma Tumor Clearance

by Christopher T. Lucido, Paola D. Vermeer, Bryant G. Wieking, Daniel W. Vermeer and John H. Lee

Vaccines 2014, 2(4), 841-853; https://doi.org/10.3390/vaccines2040841 - 10 Dec 2014

Cited by 19 | Viewed by 6625

Standard-of-care cisplatin and radiation therapy (CRT) provides significant tumor control of human papillomavirus (HPV)-mediated head and neck squamous cell carcinomas (HNSCCs); this effectiveness depends on CRT-mediated activation of the patient’s own immune system. However, despite good survival, patients suffer significant morbidity necessitating on-going [...] Read more.

Standard-of-care cisplatin and radiation therapy (CRT) provides significant tumor control of human papillomavirus (HPV)-mediated head and neck squamous cell carcinomas (HNSCCs); this effectiveness depends on CRT-mediated activation of the patient’s own immune system. However, despite good survival, patients suffer significant morbidity necessitating on-going studies to define novel therapies that alleviate this burden. Given the role of the immune system in tumor clearance, immune modulation may further potentiate the CRT-activated response while potentially decreasing morbidity. CD137, an inducible cell surface receptor found on activated T cells, is involved in differentiation and survival signaling in T cells upon binding of its natural partner (CD137L). A number of studies have shown the effectiveness of targeting this immune-stimulatory pathway in regards to tumor clearance. Here, we test its role in HPV+ HNSCC tumor clearance using a previously characterized mouse model. We show that amplification of this stimulatory pathway synergizes with CRT for enhanced tumor clearance. Interestingly, tumor clearance is further potentiated by local tumor cell expression of CD137L. Full article

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260 KiB

Open AccessReview

Peptide Vaccines for Hypertension and Diabetes Mellitus

by Hironori Nakagami, Hiroshi Koriyama and Ryuichi Morishita

Vaccines 2014, 2(4), 832-840; https://doi.org/10.3390/vaccines2040832 - 26 Nov 2014

Cited by 6 | Viewed by 9234

Abstract

Vaccines are commonly used as a preventive medicine for infectious diseases worldwide; however, the trial for an amyloid beta vaccine against Alzheimer’s disease will open a new concept in vaccination. In case of therapeutic vaccines for cancer, their targets are usually specific antigens [...] Read more.

Vaccines are commonly used as a preventive medicine for infectious diseases worldwide; however, the trial for an amyloid beta vaccine against Alzheimer’s disease will open a new concept in vaccination. In case of therapeutic vaccines for cancer, their targets are usually specific antigens in cancer cells, allowing activated cytotoxic T cells (CTLs) to attach and remove the antigen-presenting cancer cells. In our therapeutic vaccines against hypertension, the target is angiotensin II (Ang II) and induced anti-Ang II antibodies could efficiently ameliorate high blood pressure. Similarly, we developed the therapeutic vaccine against DPP4 for diabetes mellitus. However, because Ang II or DPP4 is an endogenous hormone, we must avoid autoimmune disease induced by these vaccines. Therefore, our system was used to design a therapeutic vaccine that elicits anti-Ang II or DPP4 antibodies without CTL activation against Ang II or DPP4. In this review, we will describe our concept of therapeutic vaccines for hypertension and diabetes mellitus. Full article

(This article belongs to the Special Issue Peptide Vaccine)

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906 KiB

Open AccessReview

A Systematic Review of Recent Advances in Equine Influenza Vaccination

by Romain Paillot

Vaccines 2014, 2(4), 797-831; https://doi.org/10.3390/vaccines2040797 - 14 Nov 2014

Cited by 66 | Viewed by 15418

Abstract

Equine influenza (EI) is a major respiratory disease of horses, which is still causing substantial outbreaks worldwide despite several decades of surveillance and prevention. Alongside quarantine procedures, vaccination is widely used to prevent or limit spread of the disease. The panel of EI [...] Read more.

Equine influenza (EI) is a major respiratory disease of horses, which is still causing substantial outbreaks worldwide despite several decades of surveillance and prevention. Alongside quarantine procedures, vaccination is widely used to prevent or limit spread of the disease. The panel of EI vaccines commercially available is probably one of the most varied, including whole inactivated virus vaccines, Immuno-Stimulating Complex adjuvanted vaccines (ISCOM and ISCOM-Matrix), a live attenuated equine influenza virus (EIV) vaccine and a recombinant poxvirus-vectored vaccine. Several other strategies of vaccination are also evaluated. This systematic review reports the advances of EI vaccines during the last few years as well as some of the mechanisms behind the inefficient or sub-optimal response of horses to vaccination. Full article

(This article belongs to the Special Issue Vaccine Adjuvants)

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180 KiB

Open AccessEditorial

DNA Vaccines: Recent Developments and the Future

by Britta Wahren and Margaret A. Liu

Vaccines 2014, 2(4), 785-796; https://doi.org/10.3390/vaccines2040785 - 27 Oct 2014

Cited by 27 | Viewed by 8624

Abstract

This special issue is focused on DNA vaccines, marking the two decades since the first demonstration of pre-clinical protection was published in Science (Ulmer et al.; Heterologous protection against influenza by injection of DNA encoding a viral protein. 1993). This introductory article [...] Read more.

This special issue is focused on DNA vaccines, marking the two decades since the first demonstration of pre-clinical protection was published in Science (Ulmer et al.; Heterologous protection against influenza by injection of DNA encoding a viral protein. 1993). This introductory article provides an overview of the field and highlights the observations of the articles in this special issue while placing them in the context of other recent publications. Full article

(This article belongs to the Special Issue DNA Vaccines)

400 KiB

Open AccessArticle

A Recombinant Raccoon Poxvirus Vaccine Expressing both Yersinia pestis F1 and Truncated V Antigens Protects Animals against Lethal Plague

by Tonie E. Rocke, Brock Kingstad-Bakke, Willy Berlier and Jorge E. Osorio

Vaccines 2014, 2(4), 772-784; https://doi.org/10.3390/vaccines2040772 - 27 Oct 2014

Cited by 25 | Viewed by 7102

Abstract

In previous studies, we demonstrated in mice and prairie dogs that simultaneous administration of two recombinant raccoon poxviruses (rRCN) expressing Yersinia pestis antigens (F1 and V307—a truncated version of the V protein) provided superior protection against plague challenge compared to individual [...] Read more.

In previous studies, we demonstrated in mice and prairie dogs that simultaneous administration of two recombinant raccoon poxviruses (rRCN) expressing Yersinia pestis antigens (F1 and V307—a truncated version of the V protein) provided superior protection against plague challenge compared to individual single antigen constructs. To reduce costs of vaccine production and facilitate implementation of a sylvatic plague vaccine (SPV) control program for prairie dogs, a dual antigen construct is more desirable. Here we report the construction and characterization of a novel RCN-vectored vaccine that simultaneously expresses both F1 and V307 antigens. This dual antigen vaccine provided similar levels of protection against plague in both mice and prairie dogs as compared to simultaneous administration of the two single antigen constructs and was also shown to protect mice against an F1 negative strain of Y. pestis. The equivalent safety, immunogenicity and efficacy profile of the dual RCN-F1/V307 construct warrants further evaluation in field efficacy studies in sylvatic plague endemic areas. Full article

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441 KiB

Open AccessReview

Vaccinia Virus LC16m8∆ as a Vaccine Vector for Clinical Applications

by Minoru Kidokoro and Hisatoshi Shida

Vaccines 2014, 2(4), 755-771; https://doi.org/10.3390/vaccines2040755 - 17 Oct 2014

Cited by 22 | Viewed by 7848

Abstract

The LC16m8 strain of vaccinia virus, the active ingredient in the Japanese smallpox vaccine, was derived from the Lister/Elstree strain. LC16m8 is replication-competent and has been administered to over 100,000 infants and 3,000 adults with no serious adverse reactions. Despite this outstanding safety [...] Read more.

The LC16m8 strain of vaccinia virus, the active ingredient in the Japanese smallpox vaccine, was derived from the Lister/Elstree strain. LC16m8 is replication-competent and has been administered to over 100,000 infants and 3,000 adults with no serious adverse reactions. Despite this outstanding safety profile, the occurrence of spontaneously-generated large plaque-forming virulent LC16m8 revertants following passage in cell culture is a major drawback. We identified the gene responsible for the reversion and deleted the gene (B5R) from LC16m8 to derive LC16m8Δ. LC16m8∆ is non-pathogenic in immunodeficient severe combined immunodeficiency (SCID) mice, genetically-stable and does not reverse to a large-plaque phenotype upon passage in cell culture, even under conditions in which most LC16m8 populations are replaced by revertants. Moreover, LC16m8∆ is >500-fold more effective than the non-replicating vaccinia virus (VV), Modified Vaccinia Ankara (MVA), at inducing murine immune responses against pathogenic VV. LC16m8∆, which expresses the SIV gag gene, also induced anti-Gag CD8⁺ T-cells more efficiently than MVA and another non-replicating VV, Dairen I minute-pock variants (DIs). Moreover, LC16m8∆ expressing HIV-1 Env in combination with a Sendai virus vector induced the production of anti-Env antibodies and CD8⁺ T-cells. Thus, the safety and efficacy of LC16m8∆ mean that it represents an outstanding platform for the development of human vaccine vectors. Full article

(This article belongs to the Special Issue Vaccine Vector)

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499 KiB

Open AccessReview

Self-Amplifying Replicon RNA Vaccine Delivery to Dendritic Cells by Synthetic Nanoparticles

by Kenneth C. McCullough, Panagiota Milona, Lisa Thomann-Harwood, Thomas Démoulins, Pavlos Englezou, Rolf Suter and Nicolas Ruggli

Vaccines 2014, 2(4), 735-754; https://doi.org/10.3390/vaccines2040735 - 16 Oct 2014

Cited by 27 | Viewed by 14636

Abstract

Dendritic cells (DC) play essential roles determining efficacy of vaccine delivery with respect to immune defence development and regulation. This renders DCs important targets for vaccine delivery, particularly RNA vaccines. While delivery of interfering RNA oligonucleotides to the appropriate intracellular sites for RNA-interference [...] Read more.

Dendritic cells (DC) play essential roles determining efficacy of vaccine delivery with respect to immune defence development and regulation. This renders DCs important targets for vaccine delivery, particularly RNA vaccines. While delivery of interfering RNA oligonucleotides to the appropriate intracellular sites for RNA-interference has proven successful, the methodologies are identical for RNA vaccines, which require delivery to RNA translation sites. Delivery of mRNA has benefitted from application of cationic entities; these offer value following endocytosis of RNA, when cationic or amphipathic properties can promote endocytic vesicle membrane perturbation to facilitate cytosolic translocation. The present review presents how such advances are being applied to the delivery of a new form of RNA vaccine, replicons (RepRNA) carrying inserted foreign genes of interest encoding vaccine antigens. Approaches have been developed for delivery to DCs, leading to the translation of the RepRNA and encoded vaccine antigens both in vitro and in vivo. Potential mechanisms favouring efficient delivery leading to translation are discussed with respect to the DC endocytic machinery, showing the importance of cytosolic translocation from acidifying endocytic structures. The review relates the DC endocytic pathways to immune response induction, and the potential advantages for these self-replicating RNA vaccines in the near future. Full article

(This article belongs to the Special Issue Vaccine Vector)

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512 KiB

Open AccessReview

Overview of Serological Techniques for Influenza Vaccine Evaluation: Past, Present and Future

by Claudia Maria Trombetta, Daniele Perini, Stuart Mather, Nigel Temperton and Emanuele Montomoli

Vaccines 2014, 2(4), 707-734; https://doi.org/10.3390/vaccines2040707 - 13 Oct 2014

Cited by 80 | Viewed by 14103

Abstract

Serological techniques commonly used to quantify influenza-specific antibodies include the Haemagglutination Inhibition (HI), Single Radial Haemolysis (SRH) and Virus Neutralization (VN) assays. HI and SRH are established and reproducible techniques, whereas VN is more demanding. Every new influenza vaccine needs to fulfil the [...] Read more.

Serological techniques commonly used to quantify influenza-specific antibodies include the Haemagglutination Inhibition (HI), Single Radial Haemolysis (SRH) and Virus Neutralization (VN) assays. HI and SRH are established and reproducible techniques, whereas VN is more demanding. Every new influenza vaccine needs to fulfil the strict criteria issued by the European Medicines Agency (EMA) in order to be licensed. These criteria currently apply exclusively to SRH and HI assays and refer to two different target groups—healthy adults and the elderly, but other vaccine recipient age groups have not been considered (i.e., children). The purpose of this timely review is to highlight the current scenario on correlates of protection concerning influenza vaccines and underline the need to revise the criteria and assays currently in use. In addition to SRH and HI assays, the technical advantages provided by other techniques such as the VN assay, pseudotype-based neutralization assay, neuraminidase and cell-mediated immunity assays need to be considered and regulated via EMA criteria, considering the many significant advantages that they could offer for the development of effective vaccines. Full article

(This article belongs to the Special Issue Influenza Vaccines)

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Open AccessArticle

Enhancement of Mucosal Immunogenicity of Viral Vectored Vaccines by the NKT Cell Agonist Alpha-Galactosylceramide as Adjuvant

by Shailbala Singh, Pramod N. Nehete, Guojun Yang, Hong He, Bharti Nehete, Patrick W. Hanley, Michael A. Barry and K. Jagannadha Sastry

Vaccines 2014, 2(4), 686-706; https://doi.org/10.3390/vaccines2040686 - 10 Oct 2014

Cited by 17 | Viewed by 7667

Abstract

Gene-based vaccination strategies, specifically viral vectors encoding vaccine immunogens are effective at priming strong immune responses. Mucosal routes offer practical advantages for vaccination by ease of needle-free administration, and immunogen delivery at readily accessible oral/nasal sites to efficiently induce immunity at distant gut [...] Read more.

Gene-based vaccination strategies, specifically viral vectors encoding vaccine immunogens are effective at priming strong immune responses. Mucosal routes offer practical advantages for vaccination by ease of needle-free administration, and immunogen delivery at readily accessible oral/nasal sites to efficiently induce immunity at distant gut and genital tissues. However, since mucosal tissues are inherently tolerant for induction of immune responses, incorporation of adjuvants for optimal mucosal vaccination strategies is important. We report here the effectiveness of alpha-galactosylceramide (α-GalCer), a synthetic glycolipid agonist of natural killer T (NKT) cells, as an adjuvant for enhancing immunogenicity of vaccine antigens delivered using viral vectors by mucosal routes in murine and nonhuman primate models. Significant improvement in adaptive immune responses in systemic and mucosal tissues was observed by including α-GalCer adjuvant for intranasal immunization of mice with vesicular stomatitis virus vector encoding the model antigen ovalbumin and adenoviral vectors expressing HIV env and Gag antigens. Activation of NKT cells in systemic and mucosal tissues along with significant increases in adaptive immune responses were observed in rhesus macaques immunized by intranasal and sublingual routes with protein or adenovirus vectored antigens when combined with α-GalCer adjuvant. These results support the utility of α-GalCer adjuvant for enhancing immunogenicity of mucosal vaccines delivered using viral vectors. Full article

(This article belongs to the Special Issue Vaccine Vector)

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Vaccines, Volume 2, Issue 4 (December 2014) – 9 articles , Pages 686-853

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