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

Immunization with an adenovirus-vectored TB vaccine containing Ag85A-Mtb32 effectively alleviates allergic asthma.
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Zhang Y, Feng Y, Li L, Ye X, Wang J, Wang Q, Li P, Li N, Zheng X, Gao X, Li C, Li F, Sun B, Lai K, Su Z, Zhong N, Chen L, Feng L,


Zhang Y, Feng Y, Li L, Ye X, Wang J, Wang Q, Li P, Li N, Zheng X, Gao X, Li C, Li F, Sun B, Lai K, Su Z, Zhong N, Chen L, Feng L, (click to view)

Zhang Y, Feng Y, Li L, Ye X, Wang J, Wang Q, Li P, Li N, Zheng X, Gao X, Li C, Li F, Sun B, Lai K, Su Z, Zhong N, Chen L, Feng L,

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Journal of molecular medicine (Berlin, Germany) 2018 01 0496(3-4) 249-263 doi 10.1007/s00109-017-1614-5

Abstract

Current treatments for allergic asthma primarily ameliorate symptoms rather than inhibit disease progression. Regulating the excessive T helper type 2 (Th2) responses may 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 CD4T and CD8T 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 may provide clinical benefits in allergic inflammatory airways disease.

KEY MESSAGES
•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.

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