Immunization with an adenovirus-vectored TB vaccine containing Ag85A-Mtb32 effectively alleviates allergic asthma

Current treatments for allergic asthma primarily ameliorate symptoms rather than inhibit disease progression. regulating the excessive t helper type 2 (th2) responses prevent asthma exacerbation. in this study, we investigated the protective effects of ad5-gsgam, an adenovirus vector carrying two mycobacterial antigens ag85a and mtb32, against allergic asthma. using an ovalbumin (ova)-induced asthmatic mouse model, we found that ad5-gsgam elicited much more th1-biased cd4+t and cd8+t cells than bacillus calmette-guérin (bcg). after ova challenge, ad5-gsgam-immunized mice showed significantly lowered airway inflammation in comparison with mice immunized with or without bcg. total serum immunoglobulin e and pulmonary inducible-nitric-oxide-synthase were efficiently reduced. the cytokine profiles in bronchial-alveolar-lavage-fluids (balfs) were also modulated, as evidenced by the increased level of interferon-γ (ifn-γ) and the decreased level of interleukin (il)-4, il-5, and il-13. anti-inflammatory cytokine il-10 was sharply increased, whereas pro-inflammatory cytokine il-33 was significantly decreased. importantly, exogenous il-33 abrogated the protective effects of ad5-gsgam, revealing that the suppression of il-33/st2 axis substantially contributed to protection against allergic inflammation. moreover, regulatory t cells were essential for regulating aberrant th2 responses as well as il-33/st2 axis. these results suggested that modulating the il-33/st2 axis via adenovirus-vectored mycobacterial antigen vaccination provide clinical benefits in allergic inflammatory airways disease. •ad5-gsgam elicits th1 responses and suppresses th2-mediated allergic asthma in mice. •ad5-gsgam inhibits il-33/st2 axis by reducing il-33 secretion but not ilc2 recruiting. •treg is essential for modulating th2 responses and il-33/st2 axis by ad5-gsgam.