Preexisting antibodies targeting SARS-CoV-2 S2 cross-react with commensal gut bacteria and impact COVID-19 vaccine induced immunity

Autor: Liqiu Jia, Shufeng Weng, Jing Wu, Xiangxiang Tian, Yifan Zhang, Xuyang Wang, Jing Wang, Dongmei Yan, Wanhai Wang, Fang Fang, Zhaoqin Zhu, Chao Qiu, Wenhong Zhang, Ying Xu, Yanmin Wan
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Gut Microbes, Vol 14, Iss 1 (2022)
Druh dokumentu: article
ISSN: 19490976
1949-0984
1949-0976
DOI: 10.1080/19490976.2022.2117503
Popis: The origins of preexisting SARS-CoV-2 cross-reactive antibodies and their potential impacts on vaccine efficacy have not been fully clarified. In this study, we demonstrated that S2 was the prevailing target of the preexisting S protein cross-reactive antibodies in both healthy human and SPF mice. A dominant antibody epitope was identified on the connector domain of S2 (1147-SFKEELDKYFKNHT-1160, P144), which could be recognized by preexisting antibodies in both human and mouse. Through metagenomic sequencing and fecal bacteria transplant, we demonstrated that the generation of S2 cross-reactive antibodies was associated with commensal gut bacteria. Furthermore, six P144 reactive monoclonal antibodies were isolated from naïve SPF mice and were proven to cross-react with commensal gut bacteria collected from both human and mouse. A variety of cross-reactive microbial proteins were identified using LC-MS, of which E. coli derived HSP60 and HSP70 proteins were confirmed to be able to bind to one of the isolated monoclonal antibodies. Mice with high levels of preexisting S2 cross-reactive antibodies mounted higher S protein specific binding antibodies, especially against S2, after being immunized with a SARS-CoV-2 S DNA vaccine. Similarly, we found that levels of preexisting S2 and P144-specific antibodies correlated positively with RBD binding antibody titers after two doses of inactivated SARS-CoV-2 vaccination in human. Collectively, our study revealed an alternative origin of preexisting S2-targeted antibodies and disclosed a previously neglected aspect of the impact of gut microbiota on host anti-SARS-CoV-2 immunity.
Databáze: Directory of Open Access Journals
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