Bacteroides OMV Drug Delivery Technology: Mucosal vaccine development plasmid transfer from E. coli to Bacteroides Secretion sequences - Surface of OMVs Secretion sequences – Lumen of OMVs Internal Ag Surface Ag 0 50 100 Storage at 21 o C (weeks) % Residual activity OMV stability 0 2 4 6 8 12 ~200nm dia. Bacteroides OMV Udo Wegmann, Regis Stentz, Ana Carvalho, Ariadna Clopes (QIB) • Non-replicating, stable • Needle-free delivery • Target mucosal sites • Established safety record in adults and children (MenBvac) • Elicit Ag-specific immune responses • Possess self-adjuvant properties • Relatively cheap and straightforward to produce • Delivered quickly and outside a formal clinic setting • Less reliant on trained personnel for delivery Intranasal Oral Media alone + Proteases Protected cargo Surface Ag Internal Ag
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Bacteroides OMV Drug Delivery Technology: Mucosal vaccine development
plasmid transfer from E. coli to Bacteroides
Secretion sequences - Surface of OMVs Secretion sequences – Lumen of OMVs
Internal Ag
Surface Ag
0
50
100
Storage at 21oC (weeks)
% R
esid
ual
act
ivit
y
OMV stability
0 2 4 6 8 12
~200nm dia.
Bacteroides OMV
Udo Wegmann, Regis Stentz, Ana Carvalho, Ariadna Clopes (QIB)
• Non-replicating, stable
• Needle-free delivery
• Target mucosal sites
• Established safety record in adults and children (MenBvac)
• Elicit Ag-specific immune responses
• Possess self-adjuvant properties
• Relatively cheap and straightforward to produce
• Delivered quickly and outside a formal clinic setting
• Less reliant on trained personnel for delivery
Intranasal Oral
Media alone
+ Proteases
Protected cargo
Surface Ag Internal Ag
Intranasally administered Bt-OMVs promote development of lymphoid aggregates and
germinal centres in the nasal cavity, NALT, iBALT and FALC
Control (PBS): B cells + Bt-OMVs: B cells
NC
NS
Hard Palate
NC
Anjar Kipar, James Stewart, Ana Carvalho
B cells: CD45R
T cells: CD3
DCs: Iba-1
T cells DCs B cells iBALT:
B cells
B cells
T cells
FALC:
B cells
B cells
T cells
total IgA in Salivary glandsu
g Ig
A/m
l
OM
V-om
pA
contr
ol
0.0
0.5
1.0
1.5
2.0
Total IgA in BAL
ug
Ig
A/m
l
OMV-ompA immuniz Control0
5
10
15
OMV immunized Control
OMV immunized Control
Intranasal immunisation of NHPs with Y. pestis V antigen containing OMVs – Preliminary Findings
Serum: V-IgG
BAL: V-IgA Salivary Glands: V-IgA
http://www.ebi.ac.uk/
0 7 12 21 34 56
+ Salivary glands
+ BAL
Blood and faecal samples
OMV-V (12-50ug/ml)
Immunisation schedule Oral/Intranasal
Ana Carvalho, Ariadna Clopes (QIB)
Simon Funnell (PHE)
Diane Williamson (Dstl)
(1/2560 dilution)
(1/8 dilution) (1/4 dilution)
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