A multistage Sendai virus vaccine incorporating latency-associated antigens induces protection against acute and latent tuberculosis.
Zhidong Hu, Jingxian Xia, Juan Wu, Huimin Zhao, Ping Ji, Ling Gu, Wenfei Gu, Zhenyan Chen, Jinchuan Xu, Xuejiao Huang, Jian Ma, Anke Chen, Jixi Li, Tsugumine Shu, Xiao-Yong Fan
Author Information
Zhidong Hu: Shanghai Public Health Clinical Center & Shanghai Institute of Infectious Diseases and Biosecurity, Fudan University, Shanghai, People's Republic of China.
Jingxian Xia: Shanghai Public Health Clinical Center & Shanghai Institute of Infectious Diseases and Biosecurity, Fudan University, Shanghai, People's Republic of China.
Juan Wu: Shanghai Public Health Clinical Center & Shanghai Institute of Infectious Diseases and Biosecurity, Fudan University, Shanghai, People's Republic of China.
Huimin Zhao: Shanghai Public Health Clinical Center & Shanghai Institute of Infectious Diseases and Biosecurity, Fudan University, Shanghai, People's Republic of China.
Ping Ji: Shanghai Public Health Clinical Center & Shanghai Institute of Infectious Diseases and Biosecurity, Fudan University, Shanghai, People's Republic of China.
Ling Gu: Shanghai Public Health Clinical Center & Shanghai Institute of Infectious Diseases and Biosecurity, Fudan University, Shanghai, People's Republic of China.
Wenfei Gu: Shanghai Public Health Clinical Center & Shanghai Institute of Infectious Diseases and Biosecurity, Fudan University, Shanghai, People's Republic of China.
Zhenyan Chen: Shanghai Public Health Clinical Center & Shanghai Institute of Infectious Diseases and Biosecurity, Fudan University, Shanghai, People's Republic of China.
Jinchuan Xu: Shanghai Public Health Clinical Center & Shanghai Institute of Infectious Diseases and Biosecurity, Fudan University, Shanghai, People's Republic of China.
Xuejiao Huang: Shanghai Public Health Clinical Center & Shanghai Institute of Infectious Diseases and Biosecurity, Fudan University, Shanghai, People's Republic of China.
Jian Ma: ID Pharma, Ibaraki, Japan.
Anke Chen: State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, People's Republic of China.
Jixi Li: State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, People's Republic of China.
Tsugumine Shu: ID Pharma, Ibaraki, Japan.
Xiao-Yong Fan: Shanghai Public Health Clinical Center & Shanghai Institute of Infectious Diseases and Biosecurity, Fudan University, Shanghai, People's Republic of China. ORCID
One-quarter of the world's population is infected with (). After initial exposure, more immune-competent persons develop asymptomatic latent tuberculosis infection (LTBI) but not active diseases, creates an extensive reservoir at risk of developing active tuberculosis. Previously, we constructed a novel recombinant Sendai virus (SeV)-vectored vaccine encoding two dominant antigens of , which elicited immune protection against acute infection. In this study, nine latency-associated antigens were screened as potential supplementary vaccine candidate antigens, and three antigens (Rv2029c, Rv2028c, and Rv3126c) were selected based on their immune-therapeutic effect in mice, and their elevated immune responses in LTBI human populations. Then, a recombinant SeV-vectored vaccine, termed SeV986A, that expresses three latency-associated antigens and Ag85A was constructed. In murine models, the doses, titers, and inoculation sites of SeV986A were optimized, and its immunogenicity in BCG-primed and BCG-naive mice were determined. Enhanced immune protection against the challenge was shown in both acute-infection and latent-infection murine models. The expression levels of several T-cell exhaustion markers were significantly lower in the SeV986A-vaccinated group, suggesting that the expression of latency-associated antigens inhibited the T-cell exhaustion process in LTBI infection. Hence, the multistage quarter-antigenic SeV986A vaccine holds considerable promise as a novel post-exposure prophylaxis vaccine against tuberculosis.
