Subunit Vaccine ESAT-6:c-di-AMP Delivered by Intranasal Route Elicits Immune Responses and Protects Against Mycobacterium tuberculosis Infection

Frontiers in Cellular and Infection Microbiology

Yanzhi Lu¹  Yinlan Bai¹  Jian Kang¹  Wei Zhang²  Lixin Shen³  Xuan Liang³  Huanhuan Ning⁴  Tianbing Ding⁵  Wenjie Sun⁶  Huapeng Wang⁶  Chengxuan Guo⁶ 

[1] Department of Microbiology and Pathogen Biology, Basic Medical School, Air Force Medical University, Xi’an, China;Department of Paediatrics, TangDu Hospital, Air Force Medical University, Xi’an, China;Key Laboratory of Resources Biology and Biotechnology in Western China, College of Life Sciences, Northwest University, Xi’an, China;Key Laboratory of Resources Biology and Biotechnology in Western China, College of Life Sciences, Northwest University, Xi’an, China;Department of Microbiology and Pathogen Biology, Basic Medical School, Air Force Medical University, Xi’an, China;Medical College, Xijing University, Xi’an, China;Student Brigade, Basic Medical School, Air Force Medical University, Xi’an, China;

关键词: Mycobacterium tuberculosis;    subunit vaccine;    ESAT-6;    c-di-AMP;    mucosal adjuvant;   

DOI  :  10.3389/fcimb.2021.647220

来源: Frontiers

【 摘 要 】

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) infection, remains the most common cause of death from a single infectious disease. More safe and effective vaccines are necessary for preventing the prevalence of TB. In this study, a subunit vaccine of ESAT-6 formulated with c-di-AMP (ESAT-6:c-di-AMP) promoted mucosal and systemic immune responses in spleen and lung. ESAT-6:c-di-AMP inhibited the differentiations of CD8+ T cells as well as macrophages, but promoted the differentiations of ILCs in lung. The co-stimulation also enhanced inflammatory cytokines production in MH-S cells. It was first revealed that ESAT-6 and c-di-AMP regulated autophagy of macrophages in different stages, which together resulted in the inhibition of Mtb growth in macrophages during early infection. After Mtb infection, the level of ESAT-6-specific immune responses induced by ESAT-6:c-di-AMP dropped sharply. Finally, inoculation of ESAT-6:c-di-AMP led to significant reduction of bacterial burdens in lungs and spleens of immunized mice. Our results demonstrated that subunit vaccine ESAT-6:c-di-AMP could elicit innate and adaptive immune responses which provided protection against Mtb challenge, and c-di-AMP as a mucosal adjuvant could enhance immunogenicity of antigen, especially for innate immunity, which might be used for new mucosal vaccine against TB.

【 授权许可】

CC BY