A multistage Sendai virus vaccine incorporating latency-associated antigens induces protection against acute and latent tuberculosis
| Autor: | 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 |
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| Jazyk: | angličtina |
| Rok vydání: | 2024 |
| Předmět: | |
| Zdroj: | Emerging Microbes and Infections, Vol 13, Iss 1 (2024) |
| Druh dokumentu: | article |
| ISSN: | 22221751 2222-1751 |
| DOI: | 10.1080/22221751.2023.2300463 |
| Popis: | ABSTRACTOne-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 considerable promise as a novel post-exposure prophylaxis vaccine against tuberculosis. |
| Databáze: | Directory of Open Access Journals |
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