Preexisting antibodies targeting SARS-CoV-2 S2 cross-react with commensal gut bacteria and impact COVID-19 vaccine induced immunity. (31st December 2022)

• Record Type: Journal Article
• Authors: Jia, Liqiu; Weng, Shufeng; Wu, Jing; Tian, Xiangxiang; Zhang, Yifan; Wang, Xuyang; Wang, Jing; Yan, Dongmei; Wang, Wanhai; Fang, Fang; Zhu, Zhaoqin; Qiu, Chao; Zhang, Wenhong; Xu, Ying; Wan, Yanmin
• Is Part Of: Gut microbes. Volume 14:Isuse 1(2022)
• Publication Date: 2022-12-31
• Subjects: Cross-reactive antibody -- SARS-CoV-2 -- spike protein -- commensal gut bacteria -- vaccine immunogenicity; Gastrointestinal system -- Microbiology -- Periodicals; Microbiology -- Periodicals; Intestine, Small -- Periodicals; 616.3
• DOI: 10.1080/19490976.2022.2117503
• Languages: English
• ISSNs: 1949-0984

Abstract

ABSTRACT: 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.