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Quantatitive Analysis of Conserved Sites on the SARS-CoV-2 Receptor-Binding Domain to Promote Development of Universal SARS-Like Coronavirus Vaccines

By Siling Wang, Dinghui Wu, Hualong Xiong, Juan Wang, Zimin Tang, Zihao Chen, Yizhen Wang, Yali Zhang, Dong Ying, Xue Lin, Chang Liu, Shaoqi Guo, Weikun Tian, Yajie Lin, Xiaoping Zhang, Quan Yuan, Hai Yu, Tianying Zhang, Zizheng Zheng, Ningshao Xia

Posted 11 Apr 2021
bioRxiv DOI: 10.1101/2021.04.10.439161

Although vaccines have been successfully developed and approved against SARS-CoV-2, it is still valuable to perform studies on conserved antigenic sites for preventing possible pandemic-risk of other SARS-like coronavirus in the future and prevalent SARS-CoV-2 variants. By antibodies obtained from convalescent COVID-19 individuals, receptor binding domain (RBD) were identified as immunodominant neutralizing domain that efficiently elicits neutralizing antibody response with on-going affinity mature. Moreover, we succeeded to define a quantitative antigenic map of neutralizing sites within SARS-CoV-2 RBD, and found that sites S2, S3 and S4 (new-found site) are conserved sites and determined as subimmunodominant sites, putatively due to their less accessibility than SARS-CoV-2 unique sites. P10-6G3, P07-4D10 and P05-6H7, respectively targeting S2, S3 and S4, are relatively rare antibodies that also potently neutralizes SARS-CoV, and the last mAbs performing neutralization without blocking S protein binding to receptor. Further, we have tried to design some RBDs to improve the immunogenicity of conserved sites. Our studies, focusing on conserved antigenic sites of SARS-CoV-2 and SARS-CoV, provide insights for promoting development of universal SARS-like coronavirus vaccines therefore enhancing our pandemic preparedness.

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