Broncho-Vaxom : MOA

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 OM-85 BV: a standardized
immunoactive bacterial extract
OM-85 BV is a standardized immunoactive extract of 8 species (21 strains) of
bacteria associated with RTIs

Gram Genus Strain species (number of strains)

Negative Haemophilus influenzae (1)

Moraxella catarrhalis (3)

(Branhamella)

Klebsiella pneumoniae ssp. pneumoniae (2)

pneumoniae ssp. ozaenae (1)

Positive Streptococcus pyogenes (1)

pneumoniae (4)

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sanguinis (viridans) (3)

Staphylococcus aureus (6)

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 The immune system

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Male et al. Immunology, 8th edition (2012)
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 The immune system

Main role: to seek and kill invaders

Innate system Adaptive system

• Activation against any • Response mediated

kind of invaders (non- toward specific
specific) pathogens or *Ag

• Immediate, maximal and • Lag time between

constant response exposure and maximal
response
• Phagocytic cells, *APC,
*NK cells and cytokines • B and T lymphocytes,
cytokines and antibodies
• No immunological
memory • Exposure induces
immunological memory

*APC: Antigen Presenting Cells / *NK cells: Natural Killer cells / *Ag: antigen
 Route of administration of OM-85 BV

• OM-85 BV is administered orally and activates the immune system via

the intestinal mucosa1,2

OM-85 BV administration Intestinal mucosa

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1. De Benedetto et al. Multidiscip Resp Med 2013; 2. Bessler et al. Microbial pathogens and strategies for combating them:
science, technology and education vol. 3 , 2013
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 Pattern recognition: PAMPs and PRRs

INNATE

ADAPTIVE
Natural Killer cells
Cytokine
NO secretion
Treg (IL-10)
production cytokine
secretion
T-cells
phagocytosis Cytokine
TH1 secretion
APC (IFN-γ)
macrophages
APC TH0 activation
PAMPs
differentiation
phagocytosis
Cytokine
maturation secretion
dendritic cells TH2 (IL-4)
pathogens
T-cells

maturation
PRR
B-cells B-cells activation

HQ/BRO-V/RESP/O/07/2013/003
neutrophils APC maturation

phagocytosis plasma cells Antibody

secretion

Male et al. Immunology, 8th edition (2012)

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 PAMPs and PRRs: Role in innate
immunity
• Pathogen-associated molecular
patterns (PAMPs) are motifs
associated with groups of
pathogens

• Cells of the innate immune

system recognise PAMPs via
macrophages
PAMPs
receptors known as pattern
recognition receptors (PRRs)

• A wide range
dendritic cellsof PRRs exist,
pathogens including the toll-like receptors
(TLRs) and the
PRR
NOD-like receptors (NLRs)

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neutrophils
Activation of these receptors stimulates the innate immune response to eliminate
the pathogens

Male et al. Immunology, 8th edition (2012)

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 OM-85 BV activates PRRs in a
subtle and precise manner
• OM-85 BV is a water-soluble fractions
from several strains of bacteria

• OM-85 BV functions as PAMPs and are

recognised by PRRs

• Activation of the innate immune

system by OM-85 BV is subtle
compared with triggering by invading
pathogens1

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1. Parola et al. PLoS ONE 2013
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 Neutrophils

INNATE

ADAPTIVE
Natural Killer cells
Cytokine
NO secretion
Treg (IL-10)
production cytokine
secretion
T-cells
phagocytosis Cytokine
TH1 secretion
APC (IFN-γ)
macrophages
APC TH0 activation
PAMPs
differentiation
phagocytosis
Cytokine
maturation secretion
dendritic cells TH2 (IL-4)
pathogens
T-cells

maturation
PRR
B-cells B-cells activation

HQ/BRO-V/RESP/O/07/2013/003
neutrophils APC maturation

phagocytosis plasma cells Antibody

secretion

Male et al. Immunology, 8th edition (2012)

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 Neutrophils
Activation and stimulation by OM-85 BV
OM-85 BV enhanced the bacterial killing OM-85 BV increased cytosolic [Ca2+]
activity of rabbit neutrophils in vivo1 in neutrophils1

Control OM-85 BV 400mg/kg Neutrophils + OM-85 BV

108

Calcium medium
Log10 E.coli 01

107

OM-85 BV
106 [Ca2+],

% Fura-2 saturation
nM
105

50 2mg/ml 200
0 0 4 8 12 16 20 24
1mg/ml
Time (hours)
30 0.5mg/ml
100

10 7
Log10 S. aureus 502

106

105
1 min

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104

0 0 4 8 12 16 20 24

Time (hours)

1. Nauck et al. Int J Exp Clin Chemother 1991

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 Macrophages

INNATE

ADAPTIVE
Natural Killer cells
Cytokine
NO secretion
Treg (IL-10)
production cytokine
secretion
T-cells
phagocytosis Cytokine
TH1 secretion
APC (IFN-γ)
macrophages
APC TH0 activation
PAMPs
differentiation
phagocytosis
Cytokine
maturation secretion
dendritic cells TH2 (IL-4)
pathogens
T-cells

maturation
PRR
B-cells B-cells activation

HQ/BRO-V/RESP/O/07/2013/003
neutrophils APC maturation

phagocytosis plasma cells Antibody

secretion

Male et al. Immunology, 8th edition (2012)

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 Macrophages
Activation and stimulation by OM-85 BV
OM-85 BV 7mg increased macrophage activity in
bronchoalveolar lavage (BAL) fluid from patients with chronic bronchitis 1
Chemiluminescence response of alveolar
macrophages, cpm/3 x 104 cells x 104

10

Before
OM-85 BV

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0 3 6

Time, months

1. Emmerich et al. Respiration 1990

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 Macrophages
Activation and stimulation by OM-85 BV
Reduction of bacterial colonies in BAL fluid with OM-85 BV 7mg 1

3 months after start of treatment

Before treatment
Patient with OM-85 BV
Species Colonies Species Colonies
N. catarrhalis +
7 S. viridans ++ none
C. albicans +
P. aeruginosa +
13 none
S. viridans ++
S. aureus ++
18 none
P. aeruginosa +
20 H. influenzae +++ H. influenzae ++
N. catarrhalis +
28 none
S. viridans +
N. catarrhalis +
29 S. viridans + S. viridans +
S. aureus ++

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N. catarrhalis +
30 S. viridans + none
S. albus +
38 S. aureus +++ none
1. Emmerich et al. Respiration 1990
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 Dendritic cells

INNATE

ADAPTIVE
Natural Killer cells
Cytokine
NO secretion
Treg (IL-10)
production cytokine
secretion
T-cells
phagocytosis Cytokine
TH1 secretion
APC (IFN-γ)
macrophages
APC TH0 activation
PAMPs
differentiation
phagocytosis
Cytokine
maturation secretion
dendritic cells TH2 (IL-4)
pathogens
T-cells

maturation
PRR
B-cells B-cells activation

HQ/BRO-V/RESP/O/07/2013/003
neutrophils APC maturation

phagocytosis plasma cells Antibody

secretion

Male et al. Immunology, 8th edition (2012)

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 Dendritic cells
Stimulation by OM-85 BV
OM-85 BV induced the secretion of a selection of chemokines
and cytokines in human dendritic cells1
CCL3 CCL20
1.0 5
N=7 ** N=7
** 4
** **
3
ng/ml

ng/ml
0.5 **
* 2
**
1 *
0 0
Ut LPS 10 100 1000 Ut LPS 10 100 1000
OM-85 BV µg/ml OM-85 BV µg/ml
IL-6
120
*P<0.05;**P<0.01; ** N=7
Ut=untreated; LPS=positive control 90

60
ng/ml

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10
*
5

0
Ut LPS 10 100 1000

1. Parola et al. PLoS One 2013 OM-85 BV µg/ml

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 T-cells

INNATE

ADAPTIVE
Natural Killer cells
Cytokine
NO secretion
Treg (IL-10)
production cytokine
secretion
T-cells
phagocytosis Cytokine
TH1 secretion
APC (IFN-γ)
macrophages
APC TH0 activation
PAMPs
differentiation
phagocytosis
Cytokine
maturation secretion
dendritic cells TH2 (IL-4)
pathogens
T-cells

maturation
PRR
B-cells B-cells activation

HQ/BRO-V/RESP/O/07/2013/003
neutrophils APC maturation

phagocytosis plasma cells Antibody

secretion

Male et al. Immunology, 8th edition (2012)

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 T-cells
Activation and stimulation by OM-85 BV
Oral immunisation of BALB/c mice with OM-85 BV 52.5μg induced the
upregulation of IFN-γ and downregulation of IL-41

IFN-γ IL-4

8 600
Control
OM-85 BV
6
IFN-γ (ng/ml)

400

IL-4 (pg/ml)
4

200
2

0 0

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OM-85 BV favours the TH1 immune response in mice by upregulating TH1-specific
IFN-γ and downregulating TH2-specific IL-4
1. Huber et al. Eur J Med Res 2005
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 B-cells

INNATE

ADAPTIVE
Natural Killer cells
Cytokine
NO secretion
Treg (IL-10)
production cytokine
secretion
T-cells
phagocytosis Cytokine
TH1 secretion
APC (IFN-γ)
macrophages
APC TH0 activation
PAMPs
differentiation
phagocytosis
Cytokine
maturation secretion
dendritic cells TH2 (IL-4)
pathogens
T-cells

maturation
PRR
B-cells B-cells activation

HQ/BRO-V/RESP/O/07/2013/003
neutrophils APC maturation

phagocytosis plasma cells Antibody

secretion

Male et al. Immunology, 8th edition (2012)

This slide deck is intended for use by speakers in meetings organized by OM Pharma/Vifor Pharma affiliates or partner companies.
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 B-cells
Activation and stimulation by OM-85 BV
• The effect of OM-85 BV 7mg on antibody levels in the BAL fluid of healthy
volunteers was investigated

Placebo OM-85 BV
0.4

0.4
IgA/albumin ratio

IgA/albumin ratio
p=0.028
0.2

0.2

0 0
0 90 0 90
Days Days

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In healthy subjects receiving OM-85 BV, IgA antibody levels were significantly
increased from baseline
1. Lusuardi et al. Chest 1993
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 B-cells
Activation and stimulation by OM-85 BV
IgA/albumin ratios in BAL fluid of patients with CB significantly increased after
treatment with OM-85 BV 7mg1

1.0
p=0.003
IgA/albumin ratio

0.5

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0

Before OM-85 BV After 3 months After 6 months

1. Emmerich et al. Respiration 1990

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 B-cells
Activation and stimulation by OM-85 BV
OM-85 BV increased IgG and IgA levels in children
with recurrent infections and low levels of antibodies in the blood 1

IgG 300
IgA

1.6
IgG, mg/dl, 000s

1.2 200

mg/dL, 000s
0.8

100

0.4

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0 0
Pre-treatment Post-treatment Pre-treatment Post-treatment

1. Quezada et al. J Investig Allergol Clin Immunol 1999

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 OM-85 BV improves immune
response in at-risk populations

OM-85 BV strengthens the basal activity of the immune response

– Improved alveolar macrophage activity in the BAL fluid of patients with
airway disease4
– Increased dendritic cells activation 2
– Increased antibodies in serum and in the lung of patients with airway
diseases1,3,4

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1. Quezada et al. J Investig Allergol Clin Immunol 1999; 2. Parola et al. Plos One 2013; 3. Puigdollers JM et al. Respiration.; 4.
Emmerich et al. Respiration 1990
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 Questions?

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This slide deck is intended for use by speakers in meetings organized by OM Pharma/Vifor Pharma affiliates or partner companies.
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