Download Mucosal Immunisation (Lung and Middle Ear)

Mucosal Immunisation
(Lung and Middle Ear)
Allan W Cripps AO
Mucosal Immunology Research Group
menzies.griffith.edu.au
Small Intestinal Lumen
The lungs as part of the CMIS
Antigen
T
Cells migrate
via the
afferent lymph
B
Mesenteric
Lymph Nodes
Peyer’sPatch
Thoracic Duct
Efferent
lymphatics
Mucosal Tissues
Blood
circulation
Middle Salivary Lacrimal Mammary
ear
glands glands
glands
Oral
cavity
Eye
Milk
URT
Lungs
GI
T
UGT
Small Intestinal Lumen
The lungs as part of the CMIS
Antigen
T
Cells migrate
via the
afferent lymph
B
Mesenteric
Lymph Nodes
Peyer’sPatch
Thoracic Duct
Efferent
lymphatics
Mucosal Tissues
Blood
circulation
Middle Salivary Lacrimal Mammary
ear
glands glands
glands
Oral
cavity
Eye
Milk
URT
Lungs
GI
T
UGT
Experimental Background
In 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
Multi-centre Australian trial
Clancy 2013
•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)
Time to first moderate-severe exacerbation
HI-164OV
Significantly reduced moderate-severe exacerbations (54%), corticosteroid
use (63%) hospitalisations (57%), hospitals days (59%), Antibiotic courses
(29%) and SGRQ scores
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)