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)