allan w cripps ao mucosal immunology research group menzies.griffith.edu.au mucosal immunisation...

Allan W Cripps AOMucosal Immunology Research Group

menzies.griffith.edu.au

Mucosal Immunisation(Lung and Middle Ear)

Small Intestinal Lumen

T B

Antigen

Peyer’sPatch

Cells migrate

via the

afferent lymph

Mesenteric

Lymph NodesEfferent

lymphatics

Thoracic Duct

Blood

circulation

Mucosal Tissues

Salivary

glands

Lacrimal

glands

Mammary

glands

Lungs GIT

UGT

Oral

cavity

Eye Milk

Middle

ear URT

The lungs as part of the CMIS

Small Intestinal Lumen

T B

Antigen

Peyer’sPatch

Cells migrate

via the

afferent lymph

Mesenteric

Lymph NodesEfferent

lymphatics

Thoracic Duct

Blood

circulation

Mucosal Tissues

Salivary

glands

Lacrimal

glands

Mammary

glands

Lungs GIT

UGT

Oral

cavity

Eye Milk

Middle

ear URT

The lungs as part of the CMIS

Experimental BackgroundIn an animal model of acute NTHi and Pa infection in the lungs we have demonstrated:

Mucosal immunisation results in enhanced clearance of bacteria

Mucosal immunisation modifies the inflammatory response observed as a result of infection

Primary interest in application to COPD and cystic fibrosis exacerbations and middle ear infections

Clearance of an acute NTHi infection from the lung

# p<0.05

TNFα response in BAL during acute NTHi infection

PMN and macrophage response in BAL during acute NTHi infection

Oral Immunisation against NTHi exacerbations in

patients with COPD

•HI-H005 – RCT in 320 patients with COPD (FEV1 < 60%)

•Oral immunisation with HI-164OV followed for 9 months over winter + spring

•Post-hoc analysis in those aged <64yrs (n=35) or placebo (n=56)

Multi-centre Australian trial

Clancy 2013

Significantly reduced moderate-severe exacerbations (54%), corticosteroid use (63%) hospitalisations (57%), hospitals days (59%), Antibiotic courses (29%) and SGRQ scores

HI-164OV

Time to first moderate-severe exacerbation

Conclusions

• Mucosal immunisation modulates inflammatory processes in the lung (and middle ear).

• Mucosal immunisation strategies are available against acute (and chronic) NTHi infections of the lung and middle ear.

Clearance of acute Pa infection from the lung

Immune Mechanisms in the Lung

Upper and lower respiratory epithelium Ciliated Mucocillary clearance: ~1010 particles per day

Alveolar Macrophages Poor APC but excellent “cleaners” without initiating inflammation

Neutrophils Excellent “cleaners” but cause significant collateral damage

Dendritic Cells Predominant APC in the lung

Lymphatic tissue Immune induction sites (BALT, NALT) Part of common mucosal immune network

Antigen specific responses (T cells, B cells, secretory IgA, IgG)