Conserved moonlighting protein pyruvate dehydrogenase induces robust protection against <i>Staphylococcus aureus</i> infection
Developing an effective <i>Staphylococcus aureus</i> (<i>S. aureus</i>) 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 <i>S. aureus</i> exposure may contribute to the reduction of vaccine efficacy. However, PDHC-induced protective immunity still facilitated bacterial clearance in mice previously exposed to <i>S. aureus</i>. Collectively, our findings indicate that PDHC is a promising serotype-independent vaccine candidate effective against both methicillin-sensitive and methicillin-resistant <i>S. aureus</i> isolates.
Authors
- Xuansheng Lin (ORCID: https://orcid.org/0000-0001-8877-6468)
- Xiaolei Wang (ORCID: https://orcid.org/0000-0003-3280-7282)
- C. Su
- Hin Chu (ORCID: https://orcid.org/0000-0003-2855-9837)
- Jasper Fuk‐Woo Chan (ORCID: https://orcid.org/0000-0001-6336-6657)
- Yige He
- Hua‐Rui Gong (ORCID: https://orcid.org/0000-0002-3798-9874)
- Kwok‐Yung Yuen (ORCID: https://orcid.org/0000-0002-2083-1552)
- Renhao Li (ORCID: https://orcid.org/0000-0002-6383-3240)
- Rong Li (ORCID: https://orcid.org/0000-0003-3971-1670)
- Bao‐Zhong Zhang (ORCID: https://orcid.org/0000-0002-8716-2306)
- Ying Dou (ORCID: https://orcid.org/0000-0001-9736-0392)
- Jingchu Hu (ORCID: https://orcid.org/0000-0001-6144-7226)
- Terrence Tsz‐Tai Yuen
- Jian‐Dong Huang (ORCID: https://orcid.org/0000-0001-7531-2816)
- Celia Hoi-Ching Chan
- Jian Deng
Institutions
- Shandong University (CN)
- Sun Yat-sen University (CN)
- Chinese Academy of Sciences (CN)
- Hong Kong Science and Technology Parks Corporation (HK)
- University of Hong Kong - Shenzhen Hospital (CN)
- University of Hong Kong (HK)
Publication Details
- Journal
- Proceedings of the National Academy of Sciences
- Published
- 2024-08-26
- DOI
- https://doi.org/10.1073/pnas.2321939121
- Citations
- 8
- Primary Topic
- T-cell and B-cell Immunology
- Type
- article
- Field-Weighted Citation Impact
- 1.92
Funders
- Shandong University
- Chinese Academy of Sciences
- Sun Yat-sen University
- Research Grants Council, University Grants Committee
- University of Hong Kong
- Health and Medical Research Fund
- National Key Research and Development Program of China