Huang Weili, Xu Shuqin, Shen Lifang, Chen Dan, Liu Hanmei, Tang Yuting, Liu Xiaolin, Xiao Wenxuan, Zhou Ziwei, Zhang Shifeng, Li Jixi, Fan Xiaoyong, Chu Yuefeng, Zhang Lu
State Key Laboratory of Genetics and Development of Complex Phenotypes, Department of Microbiology, School of Life Sciences, Fudan University, Shanghai 200438, China.
National Heart & Lung Institute, Imperial College London, London SW3 6LY, UK.
Vaccines (Basel). 2025 Apr 11;13(4):400. doi: 10.3390/vaccines13040400.
: Over the past two centuries, tuberculosis (TB) has been responsible for approximately one billion deaths and continues to represent a significant global health challenge. Despite extensive research efforts, fully effective strategies for the prevention or eradication of TB remain elusive, highlighting the urgent demand for novel vaccines with enhanced safety profiles and efficacy. Lipoproteins, integral surface proteins of mycobacteria, are frequently associated with virulence and display notable immunogenicity, rendering them promising candidates for vaccine development. This study investigates the potential of the mycobacterial lipoprotein, LprO, as a vaccine antigen against TB. : A pcDNA- DNA vaccine was constructed, and its immunogenicity was evaluated using a murine model. Its protective efficacy was further assessed using a ()-infected zebrafish model. Additionally, a recombinant BCG vaccine strain, BCG Japan::pNBV1-lprO, was generated. Its immunogenicity was tested in mice, and its safety was evaluated in SCID mice. Both vaccine candidates were further assessed in regard to their protective efficacy in a murine (M. tb) infection model. : The pcDNA- vaccine increased the M. tb-specific IFN-γ-secreting lymphocytes in murine spleens and prolonged the survival of zebrafish infected with . The recombinant BCG Japan::pNBV1- vaccine elicited M. tb-specific Th1-type immune responses in mice compared to the standard BCG Japan strain. Both vaccines effectively reduced the bacterial burden of M. tb in murine lungs, offering superior protection relative to the control groups. : These findings establish LprO as a compelling candidate for TB vaccine development, with both LprO-based DNA and recombinant BCG vaccines demonstrating robust protective effects against TB.
在过去的两个世纪里，结核病已导致约10亿人死亡，并且仍然是一项重大的全球健康挑战。尽管进行了广泛的研究，但预防或根除结核病的完全有效的策略仍然难以捉摸，这凸显了对具有更高安全性和有效性的新型疫苗的迫切需求。脂蛋白是分枝杆菌的 integral surface proteins，经常与毒力相关，并表现出显著的免疫原性，使其成为疫苗开发的有希望的候选者。本研究调查了分枝杆菌脂蛋白LprO作为抗结核疫苗抗原的潜力。构建了一种pcDNA-DNA疫苗，并使用小鼠模型评估其免疫原性。使用()感染的斑马鱼模型进一步评估其保护效果。此外，还产生了一种重组卡介苗疫苗株BCG Japan::pNBV1-lprO。在小鼠中测试其免疫原性，并在SCID小鼠中评估其安全性。在小鼠结核分枝杆菌感染模型中进一步评估了两种候选疫苗的保护效果。pcDNA疫苗增加了小鼠脾脏中结核分枝杆菌特异性分泌IFN-γ的淋巴细胞，并延长了感染的斑马鱼的存活时间。与标准的日本卡介苗菌株相比，重组卡介苗Japan::pNBV1疫苗在小鼠中引发了结核分枝杆菌特异性的Th1型免疫反应。两种疫苗都有效地降低了小鼠肺部结核分枝杆菌的细菌载量，相对于对照组提供了更好的保护。这些发现确立了LprO作为结核病疫苗开发的有吸引力的候选者，基于LprO的DNA疫苗和重组卡介苗疫苗都对结核病表现出强大的保护作用。 （注：原文中“integral surface proteins”可能有误，推测是“表面整合蛋白”；“()”内表述缺失；“M. tb”未明确全称，推测是“结核分枝杆菌” ，以上按推测补充后翻译，供你参考，你可根据实际情况调整。）
