An epitope vaccine derived by analyzing clinical trial samples safeguards hosts with prior exposure to <i>S. aureus</i> against reinfection
Humans, as natural carriers of <i>Staphylococcus aureus</i> (SA), have developed nonprotective immune imprints that can be reactivated by SA antigen vaccination and that contribute to the failure of SA vaccine trials. To test whether an epitope-focused vaccine strategy can overcome this issue, we explored the protective epitope of the notable SA antigen MntC. A surface loop of MntC (Loop101) was found to be essential for SA to absorb manganese(II) ion and survive oxidative stress. Our Loop101-deficient versus -competent MntC-based differential screening identified a Loop101-specific human monoclonal antibody (Hm0686). Hm0686 blocked SA from absorbing manganese(II) ion and exhibited a strong opsonophagocytic activity, suggesting that Hm0686-targeted Loop101 may be a protective epitope. A Loop101 epitope vaccine but not the whole MntC antigen protected against SA infection in mice with prior exposure-induced nonprotective imprints. Thus, this effective protective epitope-based vaccine strategy may be explored to overcome nonprotective immune imprints in humans.
Authors
- Zhen Song (ORCID: https://orcid.org/0000-0003-4724-980X)
- Yejun Zha (ORCID: https://orcid.org/0000-0001-7124-2128)
- Ping Cheng
- Quanming Zou (ORCID: https://orcid.org/0000-0002-6971-0786)
- S Ge (ORCID: https://orcid.org/0009-0006-2607-7526)
- Y. N. Zhang
- Miao Wang
- Xieyuan Jiang (ORCID: https://orcid.org/0000-0002-2993-1357)
- Weijun Zhang
- Jianxun Qi (ORCID: https://orcid.org/0000-0002-9358-4732)
- Yanyan Xu
- Jinyong Zhang (ORCID: https://orcid.org/0000-0001-9622-5834)
- Jiang Gu (ORCID: https://orcid.org/0000-0001-8035-4551)
- Feng Yang (ORCID: https://orcid.org/0000-0002-6579-9787)
- Liqun Zhao
- Hao Zeng (ORCID: https://orcid.org/0000-0002-0824-1234)
- Xin Xia
- Yeping Sun (ORCID: https://orcid.org/0009-0000-2708-2905)
- Yun Yang (ORCID: https://orcid.org/0000-0002-9413-1487)
- Ping Luo
- Yu Wang (ORCID: https://orcid.org/0000-0001-9893-4335)
- Naiyan Zeng
- Maoqi Gong (ORCID: https://orcid.org/0009-0008-1699-4835)
- Xiaokai Zhang (ORCID: https://orcid.org/0000-0002-7440-9541)
- Hua Jing
- Zhuo Zhao (ORCID: https://orcid.org/0000-0003-3130-3648)
- Yulu Chen
Institutions
- Army Medical University (CN)
- Chinese Academy of Sciences (CN)
- Peking University (CN)
- Chengdu Medical College (CN)
- Beijing Jishuitan Hospital (CN)
- Tibet Autonomous Region People's Hospital (CN)
- Institute of Microbiology (CN)
Publication Details
- Journal
- Science Translational Medicine
- Published
- 2025-08-20
- DOI
- https://doi.org/10.1126/scitranslmed.adr7464
- Citations
- 3
- Primary Topic
- Antimicrobial Resistance in Staphylococcus
- Type
- article
- Field-Weighted Citation Impact
- 4.19