A steep rise in Omicron reinfection cases suggests that this variant has increased immune evasion ability. To evaluate its antigenicity relationship with other variants, antisera from guinea pigs immunized with spike protein of SARS-CoV-2 variants of concern (VOCs) and variants of interest (VOIs) were cross-tested against pseudotyped variants. The neutralization activity against Omicron was markedly reduced when other VOCs or VOIs were used as immunogens, and Omicron (BA.1)-elicited sera did not efficiently neutralize the other variants. However, a Beta or Omicron booster, when administered as the 4th dose 3-months after the 3rd dose of any of the variants, could elicit broad neutralizing antibodies against all of the current variants including Omicron BA.1. Further analysis with 280 available antigen–antibody structures and quantification of immune escape from 715 reported neutralizing antibodies provide explanations for the observed differential immunogenicity. Three distinct clades predicted using an in silico algorithm for clustering of sarbecoviruses based on immune escape provide key information for rational design of vaccines.

Omicron 再感染病例的急剧上升表明这种变体增加了免疫逃避能力。为了评估其与其他变体的抗原性关系，用 SARS-CoV-2 关注变体 (VOC) 和感兴趣变体 (VOI) 的刺突蛋白免疫豚鼠的抗血清与假型变体进行了交叉测试。当使用其他 VOC 或 VOI 作为免疫原时，针对 Omicron 的中和活性显着降低，并且 Omicron (BA.1) 引发的血清不能有效地中和其他变体。然而，当任何变体的第 3 剂后 3 个月作为第 4 剂施用时，Beta 或 Omicron 加强剂可以引发针对包括 Omicron BA.1 在内的所有当前变体的广泛中和抗体。对 280 种可用抗原抗体结构的进一步分析和对 715 种报告的中和抗体的免疫逃逸的量化为观察到的差异免疫原性提供了解释。使用基于免疫逃逸的 sarbecoviruses 聚类的计算机算法预测的三个不同的进化枝为疫苗的合理设计提供了关键信息。