School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.
Clinical Oncology Center, The University of Hong Kong-Shenzhen Hospital, Shenzhen, People's Republic of China.
Proc Natl Acad Sci U S A. 2024 Sep 3;121(36):e2321939121. doi: 10.1073/pnas.2321939121. Epub 2024 Aug 26.
Developing an effective () vaccine has been a challenging endeavor, as demonstrated by numerous failed clinical trials over the years. In this study, we formulated a vaccine containing a highly conserved moonlighting protein, the pyruvate dehydrogenase complex E2 subunit (PDHC), and showed that it induced strong protective immunity against epidemiologically relevant staphylococcal strains in various murine disease models. While antibody responses contributed to bacterial control, they were not essential for protective immunity in the bloodstream infection model. Conversely, vaccine-induced systemic immunity relied on γδ T cells. It has been suggested that prior exposure may contribute to the reduction of vaccine efficacy. However, PDHC-induced protective immunity still facilitated bacterial clearance in mice previously exposed to . Collectively, our findings indicate that PDHC is a promising serotype-independent vaccine candidate effective against both methicillin-sensitive and methicillin-resistant isolates.
开发有效的()疫苗一直是一项具有挑战性的工作，多年来无数临床试验的失败就证明了这一点。在这项研究中，我们制备了一种包含高度保守的 moonlighting 蛋白（丙酮酸脱氢酶复合物 E2 亚基，PDHC）的疫苗，并表明它在各种小鼠疾病模型中诱导了针对具有流行病学相关性的葡萄球菌菌株的强烈保护性免疫。虽然抗体反应有助于控制细菌，但在血流感染模型中，它们对保护性免疫并非必需。相反，疫苗诱导的全身免疫依赖于γδ T 细胞。有人认为，先前的()暴露可能会降低疫苗的效力。然而，在先前接触过的小鼠中，PDHC 诱导的保护性免疫仍然有助于清除细菌。总的来说，我们的研究结果表明，PDHC 是一种有前途的、与血清型无关的疫苗候选物，对耐甲氧西林敏感和耐甲氧西林葡萄球菌分离株均有效。
