Streptococcus pneumoniae vaccine, Prevenar, utilises Tregs to suppress Asthma (140.2)

Abstract

Abstract Our recent finding that exposure to Streptococcus pneumoniae may suppress pro-asthmatic responses led us to investigate whether the current human S. pneumoniae vaccines may be used to suppress asthma using mouse models of ovalbumin-(OVA)-induced allergic airways disease (AAD). AAD was induced by intraperitoneal sensitisation and intranasal challenge with OVA. At the time of OVA sensitisation, Prevenar or Pneumovax were delivered intranasally either with or without CpG. Prevenar, but not Pneumovax, suppressed hallmark features of AAD, including eosinophil influx, OVA-specific T helper (Th) 2 cytokine release, mucus hypersecretion, total serum IgE and airways hyperresponsiveness. We then investigated whether regulatory T cells (Tregs) were important in the suppression of AAD. Prevenar increased the number of CD4+CD25+FoxP3+ expressing Tregs in the lungs, lymph nodes and spleens. The release of immuno-suppressive cytokines IL-10 and TGF-â from lymph nodes was reduced. However, Prevenar increased expression of CD103 and CTLA-4 on CD4+CD25+FoxP3+ cells. Proliferation assays demonstrated that Tregs suppressed allergic effector T cell proliferation regardless of Prevenar treatment. In conclusion, a currently available human vaccine increases the infiltration of Tregs and suppresses AAD, and may be useful as a novel therapy for asthma.