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

Emerg Microbes Infect. 2024 Dec;13(1):2300463. doi: 10.1080/22221751.2023.2300463. Epub 2024 Jan 4.

Abstract

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 considerable promise as a novel post-exposure prophylaxis vaccine against tuberculosis.

Keywords: BCG; Sendai virus; Suberculosis; latent infection; multistage; post-exposure prophylaxis; vaccine.

MeSH terms

  • Animals
  • Antigens, Bacterial / genetics
  • BCG Vaccine
  • Humans
  • Latent Tuberculosis* / prevention & control
  • Mice
  • Mycobacterium tuberculosis* / genetics
  • Sendai virus / genetics
  • Tuberculosis* / microbiology
  • Vaccines, Synthetic / genetics

Substances

  • BCG Vaccine
  • Antigens, Bacterial
  • Vaccines, Synthetic

Grants and funding

This research was funded by the National Key Research and Development Program of China (2021YFC2301503, 2022YFC2302900), National Natural and Science Foundation of China (82171815, 82171739, 81873884), Shanghai Municipal Health Bureau (2022XD060) and Shanghai Science and Technology Commission (19XD1403100).