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

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.

Potential of antibody pair targeting conserved antigenic sites in diagnosis of SARS-CoV-2 variants infection

“…40 mAbs targeting SARS-CoV-2 RBD protein were obtained from convalescent COVID-19 patients ( Wang et al, 2021b ). It is known that successful detection of the target antigen by sandwich enzyme linked immunosorbent assay (ELISA) requires the optimal antibody pairs consisting the capture antibody and detection antibody, which should target different antigenic sites.…”

A proposed workflow for proactive virus surveillance and prediction of variants for vaccine design

“…Lab-based assays can also be performed to identify epitopes for vaccine targets that would be less prone to mutations by finding epitopes and antibodies that have high binding affinities across related viral species. Recently, Wang and colleagues identified the main antigens of the SARS-CoV-2 spike (S) protein targeted by the immune system, which were distinct from antigens that are more conserved between SARS-CoV-2 and SARS-CoV-1 [ 42 ]. By eliminating the main epitopes in a lab strain of the virus and infecting mice, the mouse immune cells produced antibodies that targeted the conserved antigens and were more broadly neutralizing against both SARS-CoV species.…”