Yunlong Cao - Broad-spectrum SARS-CoV-2 Therapeutics and Prophylactics designed based on Viral Evolu

In this report, investigator Yunlong Cao systematically introduced the work conducted by his group about SARS-CoV-2 evolution prediction and the development of broadly neutralizing antibodies. He pointed out that SARS-CoV-2 is undergoing continuous evolution, giving rise to numerous immune-evasive mutants. Furthermore, the pace of viral mutation surpasses that of vaccine and antibody drug development. To address this issue, they reported a series of pioneering efforts on predicting the evolutionary trends of SARS-CoV-2. They developed a high-throughput deep mutational scanning (DMS) technique to systematically analyze the antibody escape sites of SARS-CoV-2 receptor-binding domain (RBD). With the characterization of thousands of SARS-CoV-2-specific monoclonal antibodies isolated from convalescent and vaccinated individuals, they successfully predicted the prevalence of various mutant strains, including BQ.1.1, CH.1.1, and XBB subvariants. Currently, this approach has been widely applied in monitoring the emergence of concerning mutations of SARS-CoV-2 by the community. Subsequently, Cao introduced their rational identification of a broad-spectrum neutralizing antibody, SA55, which was isolated from individuals who had recovered from SARS in 2003 and received three doses of CoronaVac, by high-throughput single-cell V(D)J sequencing and DMS epitope mapping. SA55 has already been transferred to SINOVAC for clinical development. Finally, he provided insights into future strategies for the development of broad-spectrum COVID vaccines, emphasizing the feasibility of designing broad-spectrum vaccines based on the prediction of RBD mutational hotspots.