Many studies have examined the impact of SARS-CoV-2 variants on neutralizing antibody activity after they have become dominant strains. Here, we evaluate the consequences of further viral evolution. We demonstrate mechanisms through which the SARS-CoV-2 receptor binding domain (RBD) can tolerate large numbers of simultaneous antibody escape mutations and show that pseudotypes containing up to seven mutations, as opposed to the one to three found in previously studied variants of concern, are more resistant to neutralization by therapeutic antibodies and serum from vaccine recipients. We identify an antibody that binds the RBD core to neutralize pseudotypes for all tested variants but show that the RBD can acquire an N-linked glycan to escape neutralization. Our findings portend continued emergence of escape variants as SARS-CoV-2 adapts to humans.

Online ahead of print.

该研究预测了 SARS-CoV-2 未来的进化策略，发现了几种可能的变异，这些变异使病毒能够逃避免疫防御，包括通过感染或接种疫苗获得的自然免疫，以及基于抗体的治疗。