An epitope vaccine derived by analyzing clinical trial samples safeguards hosts with prior exposure to S. aureus against reinfection

IF 14.6 1区医学 Q1 CELL BIOLOGY

Science Translational Medicine Pub Date : 2025-08-20 DOI:10.1126/scitranslmed.adr7464

Xiaokai Zhang, Shuang Ge, Yu Wang, Miao Wang, Yanyan Xu, Yulu Chen, Zhen Song, Liqun Zhao, Jinyong Zhang, Jianxun Qi, Yeping Sun, Jiang Gu, Zhuo Zhao, Xieyuan Jiang, Maoqi Gong, Yejun Zha, Yun Yang, Haiming Jing, Feng Yang, Ni Zeng, Xin Xia, Yanhao Zhang, Ping Luo, Weijun Zhang, Ping Cheng, Hao Zeng, Quanming Zou

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Abstract

Humans, as natural carriers of Staphylococcus aureus (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.

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通过分析临床试验样本获得的表位疫苗可保护先前暴露于金黄色葡萄球菌的宿主免受再感染

人类作为金黄色葡萄球菌（SA）的天然携带者，已经产生了非保护性的免疫印记，可以通过SA抗原接种重新激活，这导致了SA疫苗试验的失败。为了测试表位聚焦疫苗策略是否可以克服这一问题，我们探索了SA抗原MntC的保护性表位。MntC的一个表面环（Loop101）被发现是SA吸收锰（II）离子和存活氧化应激所必需的。我们基于loop101缺陷与正常mntc的差异筛选鉴定了一种loop101特异性的人单克隆抗体（Hm0686）。Hm0686阻断SA对锰离子的吸收，表现出较强的自噬活性，提示Hm0686靶向的Loop101可能是一个保护性表位。在先前暴露诱导的非保护性印记小鼠中，Loop101表位疫苗可保护SA感染，而不是整个MntC抗原。因此，可以探索这种有效的保护性基于表位的疫苗策略来克服人类的非保护性免疫印记。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Science Translational Medicine CELL BIOLOGY-MEDICINE, RESEARCH & EXPERIMENTAL

CiteScore

26.70

自引率

1.20%

发文量

309

审稿时长

1.7 months

期刊介绍： Science Translational Medicine is an online journal that focuses on publishing research at the intersection of science, engineering, and medicine. The goal of the journal is to promote human health by providing a platform for researchers from various disciplines to communicate their latest advancements in biomedical, translational, and clinical research. The journal aims to address the slow translation of scientific knowledge into effective treatments and health measures. It publishes articles that fill the knowledge gaps between preclinical research and medical applications, with a focus on accelerating the translation of knowledge into new ways of preventing, diagnosing, and treating human diseases. The scope of Science Translational Medicine includes various areas such as cardiovascular disease, immunology/vaccines, metabolism/diabetes/obesity, neuroscience/neurology/psychiatry, cancer, infectious diseases, policy, behavior, bioengineering, chemical genomics/drug discovery, imaging, applied physical sciences, medical nanotechnology, drug delivery, biomarkers, gene therapy/regenerative medicine, toxicology and pharmacokinetics, data mining, cell culture, animal and human studies, medical informatics, and other interdisciplinary approaches to medicine. The target audience of the journal includes researchers and management in academia, government, and the biotechnology and pharmaceutical industries. It is also relevant to physician scientists, regulators, policy makers, investors, business developers, and funding agencies.