Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Efficacy and Immunogenicity of rKVAC85B in a BCG Prime-Boost Regimen Against H37Rv and HN878 Tuberculosis Strains

Version 1 : Received: 19 February 2024 / Approved: 6 March 2024 / Online: 6 March 2024 (11:04:56 CET)

How to cite: Shin, E.; Yun, J.; Lee, Y.; Cha, H.; Kim, S.; Shin, S.; Lee, S.; Chung, G.T.; Kim, D.; Yoo, J.S.; Kim, J.; Jeong, H. Efficacy and Immunogenicity of rKVAC85B in a BCG Prime-Boost Regimen Against H37Rv and HN878 Tuberculosis Strains. Preprints 2024, 2024030351. https://doi.org/10.20944/preprints202403.0351.v1 Shin, E.; Yun, J.; Lee, Y.; Cha, H.; Kim, S.; Shin, S.; Lee, S.; Chung, G.T.; Kim, D.; Yoo, J.S.; Kim, J.; Jeong, H. Efficacy and Immunogenicity of rKVAC85B in a BCG Prime-Boost Regimen Against H37Rv and HN878 Tuberculosis Strains. Preprints 2024, 2024030351. https://doi.org/10.20944/preprints202403.0351.v1

Abstract

Mycobacterium tuberculosis was responsible for 1.3 million deaths worldwide in 2022. Bacillus Calmette-Guérin (BCG) is the only licensed vaccine against tuberculosis (TB); however, it has limited protective efficacy in adults. In this study, we constructed a recombinant vaccinia virus expressing Ag85B from M. tuberculosis using a novel attenuated vaccinia virus (KVAC103). We then analyzed the immunogenicity of prime-boost inoculation strategies using recombinant KVAC103 expressing Ag85B (rKVAC85B) compared to BCG. In both the rKVAC85B prime-boost and the BCG prime-rKVAC85B boost inoculation regimens, rKVAC85B induced the generation of specific IgG and the secretion of IFN-γ by immune cells. In vitro analysis of Mycobacterium growth inhibition revealed a comparable immune-mediated pattern of outcomes. Furthermore, bacterial loads in the lungs were significantly lower in mice inoculated with the BCG prime-rKVAC85B boost, than in the BCG-only group following a rechallenge infection with both H37Rv and HN878 strains of M. tuberculosis. These findings collectively suggest that KVAC103, incorporated into a viral vector, is a promising candidate for a novel TB vaccine platform that is effective against multiple TB strains, including H37Rv and HN878, and that rKVAC85B effectively stimulates immune responses against TB infection.

Keywords

Mycobacterium tuberculosis; tuberculosis; vaccine; attenuated vaccinia virus; Antigen 85B; immunogenicity; bacterial loads

Subject

Biology and Life Sciences, Immunology and Microbiology

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