Conserved moonlighting protein pyruvate dehydrogenase induces robust protection against Staphylococcus aureus infection

• 成果类型: Article
• 署名作者: Wang, Xiaolei; Dou, Ying; Hu, Jingchu; Chan, Celia Hoi- Ching; Li, Renhao; Rong, Li; Gong, Huarui; Deng, Jian; Yuen, Terrence Tsz- Tai; Lin, Xuansheng; He, Yige; Su, Canhui; Zhang, Bao - Zhong; Chan, Jasper Fuk- Woo; Yuen, Kwok - Yung; Chu, Hin; Huang, Jian - Dong
• 署名单位: University of Hong Kong; University of Hong Kong; University of Hong Kong; Chinese Academy of Sciences; Shenzhen Institute of Advanced Technology, CAS; Shandong University; University of Hong Kong; University of Hong Kong; University of Hong Kong; Sun Yat Sen University; University of Hong Kong
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-9745
• DOI: 10.1073/pnas.2321939121
• 发表日期: 2024-09-03
• 关键词: delta-t-cells; immune-responses; vaccine; population; mice

摘要

Developing an effective Staphylococcus aureus (S. aureus) 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 gamma delta T cells. It has been suggested that prior S. aureus exposure may contribute to the reduction of vaccine efficacy. However, PDHC- induced protective immunity still facilitated bacterial clearance in mice previously exposed to S. aureus. Collectively, our findings indicate that PDHC is a promising serotype- independent vaccine candidate effective against both methicillin- sensitive and methicillin- resistant S. aureus isolates.