A multistage Sendai virus vaccine incorporating latency-associated antigens induces protection against acute and latent tuberculosis

作者：Zhidong Hu, Jing-xian 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 · 发表于：Emerging Microbes & Infections · 年份：2024 · DOI：10.1080/22221751.2023.2300463 · 被引用次数：16 · 研究领域：Tuberculosis Research and Epidemiology、Immunodeficiency and Autoimmune Disorders、Pneumocystis jirovecii pneumonia detection and treatment

One-quarter of the world’s population is infected with Mycobacterium tuberculosis (Mtb). 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 Mtb, which elicited immune protection against acute Mtb infection. In this study, nine Mtb 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 Mtb 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 c...