Shin Eunkyung, Yun Jin-Seung, Lee Young-Ran, Cha Hye-Ran, Kim Soo-Min, Shin Sung-Jae, Lee Sang-Won, Chung Gyung Tae, Kim Dokeun, Yoo Jung Sik, Kim Jong-Seok, Jeong Hye-Sook
National Institute of Infectious Diseases, National Institute of Health, Korea Disease Control and Prevention Agency, CheongJu, Chungbuk, Republic of Korea.
Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea.
PLoS One. 2025 May 14;20(5):e0322147. doi: 10.1371/journal.pone.0322147. eCollection 2025.
Mycobacterium tuberculosis infection accounted 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 rKVAC85B prime-boost and BCG prime-rKVAC85B boost inoculation regimens, rKVAC85B induced the generation of specific immunoglobulin G (IgG) and secretion of interferon-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 the development of a novel TB vaccine platform that is effective against multiple M. tuberculosis strains, including H37Rv and HN878, and that rKVAC85B effectively stimulates immune responses against M. tuberculosis infection.
2022年，全球有130万人死于结核分枝杆菌感染。卡介苗（BCG）是唯一获得许可的抗结核疫苗；然而，它在成年人中的保护效果有限。在本研究中，我们使用一种新型减毒痘苗病毒（KVAC103）构建了一种表达结核分枝杆菌Ag85B的重组痘苗病毒。然后，我们分析了与卡介苗相比，使用表达Ag85B的重组KVAC103（rKVAC85B）进行初免-加强接种策略的免疫原性。在rKVAC85B初免-加强和卡介苗初免-rKVAC85B加强接种方案中，rKVAC85B均诱导了特异性免疫球蛋白G（IgG）的产生以及免疫细胞分泌干扰素-γ。对结核分枝杆菌生长抑制的体外分析显示，两种方案的免疫介导结果模式相当。此外，在用结核分枝杆菌H37Rv和HN878菌株再次感染后，接种卡介苗初免-rKVAC85B加强的小鼠肺部细菌载量显著低于仅接种卡介苗的组。这些发现共同表明，整合到病毒载体中的KVAC103是开发新型结核疫苗平台的有前景的候选者，该平台对包括H37Rv和HN878在内的多种结核分枝杆菌菌株有效，并且rKVAC85B能有效刺激针对结核分枝杆菌感染的免疫反应。
