Pneumococcal conjugate vaccine-induced regulatory T cells suppress the development of allergic airways disease.
BACKGROUND
Infections with some bacteria, including Streptococcus pneumoniae, have been associated with a reduced incidence of asthma. Components of S pneumoniae may have the potential to modulate allergic inflammatory responses and suppress the development of asthma.


OBJECTIVE
To determine if human S pneumoniae vaccines have the potential to suppress asthma by elucidating their effect on allergic airways disease (AAD) in mouse models.


METHODS
AAD was induced in BALB/c mice by intraperitoneal sensitisation and intranasal challenge with ovalbumin. Pneumococcal conjugate or polysaccharide vaccines were administered at the time of sensitisation or during established AAD. Hallmark features of AAD were assessed. Levels of regulatory T cells (Tregs) were quantified by fluorescence-activated cell sorting, and their immunoregulatory capacity was assessed using proliferation assays and anti-CD25 antibody treatment.


RESULTS
Intranasal administration of the conjugate vaccine, but not the polysaccharide vaccine, suppressed the hallmark features of AAD, including: eosinophilic and T helper 2-mediated inflammation; airway hyper-responsiveness; circulating immunoglobulin E (IgE) levels; and mucus hypersecretion. Intramuscular administration of the conjugate vaccine had limited protective effects. The conjugate vaccine increased Tregs in the lung-draining lymph nodes, lung and spleen. Furthermore, conjugate vaccine-induced Tregs had an enhanced capacity to suppress T effector responses. Anti-CD25 administration reversed the suppressive effects of the conjugate vaccine.


CONCLUSIONS
A currently available human conjugate vaccine suppresses the hallmark features of AAD through the induction of Tregs. Thus targeted administration may provide a novel immunoregulatory treatment for asthma.
Thorburn
Alison N
AN
Centre for Asthma and Respiratory Disease and Hunter Medical Research Institute and The University of Newcastle, Newcastle, New South Wales, Australia.
O'Sullivan
Brendan J
BJ
Thomas
Ranjeny
R
Kumar
Rakesh K
RK
Foster
Paul S
PS
Gibson
Peter G
PG
Hansbro
Philip M
PM
D000818:Animals; D001249:Asthma / Q000276:immunology / Q000517:prevention & control*; D018801:CD2 Antigens / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D007108:Immune Tolerance; D007273:Injections, Intramuscular; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D022242:Pneumococcal Vaccines / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology; D018074:Vaccines, Conjugate / Q000276:immunology
D018801:CD2 Antigens; D022242:Pneumococcal Vaccines; D018074:Vaccines, Conjugate; D010047:Ovalbumin