Gurmessa Sintayehu Kebede, Choi Han-Gyu, Back Yong Woo, Jiang Zongyou, Pham Thuy An, Choi Seunga, Kim Hwa-Jung
Department of Microbiology and Medical Science, College of Medicine, Chungnam National University, Daejeon, South Korea.
Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR, USA.
NPJ Vaccines. 2025 Jan 31;10(1):20. doi: 10.1038/s41541-025-01077-1.
While many novel candidates for tuberculosis vaccines are presently undergoing pre-clinical or clinical trials, none of them have been able to eliminate infection entirely. In this study, we engineered a potent chimeric protein vaccine candidate, Rv2299cD2D3-ESAT-6-Ag85B (REA), which induced Th1 and Th17 responses via dendritic cell maturation. REA-activated macrophages operated the killing mechanisms of Mycobacterium tuberculosis (MTB), such as phagosomal maturation and phagolysosome fusion, through the (PI3K)-p38 MAPK-Ca-NADPH oxidase pathway. Dendritic cells and macrophages activated by REA elicited synergistic anti-mycobacterial responses. Notably, REA-immunized mice suppressed MTB growth to undetectable levels at 16 weeks post-infection, which was supported by gross and pathologic findings and acid-fast staining of the lung tissues, and maintained antigen-specific multifunctional IFN-γIL-2TNF-α CD4 T and long-lasting T cells producing cytokines in the tissues. Our findings suggest that REA is an outstanding prime prophylactic vaccine candidate against tuberculosis.
虽然目前许多新型结核病疫苗候选物正在进行临床前或临床试验，但它们都无法完全消除感染。在本研究中，我们构建了一种有效的嵌合蛋白疫苗候选物Rv2299cD2D3-ESAT-6-Ag85B（REA），其通过树突状细胞成熟诱导Th1和Th17反应。REA激活的巨噬细胞通过（PI3K）-p38 MAPK-Ca-NADPH氧化酶途径发挥结核分枝杆菌（MTB）的杀伤机制，如吞噬体成熟和吞噬溶酶体融合。REA激活的树突状细胞和巨噬细胞引发协同抗分枝杆菌反应。值得注意的是，REA免疫的小鼠在感染后16周将MTB生长抑制到检测不到的水平，这得到了大体和病理结果以及肺组织抗酸染色的支持，并在组织中维持了抗原特异性多功能IFN-γIL-2TNF-α CD4 T细胞和产生细胞因子的持久T细胞。我们的研究结果表明，REA是一种出色的预防结核病的初免疫苗候选物。
