Seo Hyejun, Kim Byung-Jun, Oh Jaehun, Jung Sangkwon, Lee Ju-Young, Kim Bum-Joon
Department of Microbiology and Immunology, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea; Cancer Research Institute, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea; Seoul National University Medical Research Center (SNUMRC), Seoul 03080, Republic of Korea.
Department of Microbiology and Immunology, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea.
Vaccine. 2025 Feb 15;47:126710. doi: 10.1016/j.vaccine.2025.126710. Epub 2025 Jan 8.
Tuberculosis (TB) remains a significant global health issue due to the limited efficacy of the Bacillus Calmette-Guérin (BCG) vaccine, highlighting the need for the development of an improved TB vaccine. In this study, we created a novel TB subunit vaccine consisting of TB-secreted chorismate mutase (TBCM) (Rv1885c) and a hepatitis B virus (HBV)-derived peptide (Poly6), which elicits Type I interferon responses, both with and without an alum adjuvant. We evaluated the immunogenicity, protective efficacy, and therapeutic efficacy of this vaccine candidate in an in vivo mouse model. Our results revealed that subcutaneous vaccination with TBCM combined with Poly6 induced stronger antigen-specific humoral and cell-mediated immune responses than TBCM alone or TBCM combined with alum adjuvant. Furthermore, adding the alum adjuvant to TBCM combined with Poly6 significantly enhanced antigen-specific immune responses. Subcutaneous vaccination with TBCM combined with both Poly6 and alum adjuvants effectively protected mice against Mycobacterium tuberculosis (Mtb) K strain infection, demonstrating its potential as a TB vaccine. Additionally, this vaccine platform exhibited therapeutic potential by significantly reducing bacterial loads and lung inflammation in mice previously infected with the virulent Mtb K strain. In conclusion, our findings suggest that TBCM is highly immunogenic in mice and that TBCM combined with both Poly6 and alum adjuvants represents a promising vaccine platform for TB prevention and treatment.
由于卡介苗（BCG）疫苗的疗效有限，结核病（TB）仍然是一个重大的全球健康问题，这凸显了开发改进型结核病疫苗的必要性。在本研究中，我们创建了一种新型结核病亚单位疫苗，其由结核分枝杆菌分泌的分支酸变位酶（TBCM）（Rv1885c）和一种源自乙型肝炎病毒（HBV）的肽（Poly6）组成，无论有无明矾佐剂，该疫苗均可引发I型干扰素反应。我们在体内小鼠模型中评估了这种候选疫苗的免疫原性、保护效力和治疗效力。我们的结果显示，与单独的TBCM或TBCM与明矾佐剂联合使用相比，TBCM与Poly6联合进行皮下接种可诱导更强的抗原特异性体液免疫和细胞介导的免疫反应。此外，在TBCM与Poly6联合使用时添加明矾佐剂可显著增强抗原特异性免疫反应。TBCM与Poly6和明矾佐剂联合进行皮下接种可有效保护小鼠免受结核分枝杆菌（Mtb）K株感染，证明了其作为结核病疫苗的潜力。此外，该疫苗平台通过显著降低先前感染强毒Mtb K株的小鼠体内的细菌载量和肺部炎症，展现出治疗潜力。总之，我们的研究结果表明，TBCM在小鼠中具有高度免疫原性，并且TBCM与Poly6和明矾佐剂联合使用代表了一种用于结核病预防和治疗的有前景的疫苗平台。
