Pneumococcal conjugate vaccine-induced regulatory T cells suppress the development of allergic airways disease.

摘要

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. OBJECTIVES: 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.