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

Wang, S.; Wu, D.; Xiong, H.; Wang, J.; Tang, Z.; Chen, Z.; Wang, Y.; Zhang, Y.; Ying, D.; Lin, X.; Liu, C.; Guo, S.; Tian, W.; Lin, Y.; Zhang, X.; Yuan, Q.; Yu, H.; Zhang, T.; Zheng, Z.; Xia, N.

doi:10.1101/2021.04.10.439161

bioRxiv · 10.1101/2021.04.10.439161

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

Wang, S.·Wu, D.·Xiong, H.·Wang, J.·Tang, Z.·Chen, Z.·Wang, Y.·Zhang, Y.·Ying, D.·Lin, X.·Liu, C.·Guo, S.·Tian, W.·Lin, Y.·Zhang, X.·Yuan, Q.·Yu, H.·Zhang, T.·Zheng, Z.·Xia, N.

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Abstract

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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Wang, S., Wu, D., Xiong, H., Wang, J., Tang, Z., Chen, Z., Wang, Y., Zhang, Y., Ying, D., Lin, X., Liu, C., Guo, S., Tian, W., Lin, Y., Zhang, X., Yuan, Q., Yu, H., Zhang, T., Zheng, Z., Xia, N.. 2021-04-11. Quantatitive Analysis of Conserved Sites on the SARS-CoV-2 Receptor-Binding Domain to Promote Development of Universal SARS-Like Coronavirus Vaccines. https://doi.org/10.1101/2021.04.10.439161

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