Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant.

基于 SARS-CoV-2 刺突蛋白的疫苗是公共卫生应对 COVID-19 的基石。超突变、传染性日益增强的关注变体 (VOC) 的出现威胁到了这一策略。 Omicron (B.1.1.529) 是要描述的第五种 VOC，其刺突中含有多个氨基酸突变，其中一半位于受体结合域内。在这里，我们使用接种 ChAdOx1、BNT162b2 和 mRNA-1273 的个体血清证明 Omicron BA.1 和 BA.2 变体在体外可显着规避中和作用。这些数据反映了现实世界疫苗有效性的大幅降​​低，而加强疫苗接种可以部分恢复这种有效性。 Omicron 变体 BA.1 和 BA.2 在体外不会诱导细胞合胞体，并且有利于独立于 TMPRSS2 的内体进入途径，这些表型映射到刺突蛋白的不同区域。细胞融合受损是由受体结合​​域决定的，而内体进入则映射到 S2 域。抗原性和复制生物学的这种显着变化可能是 Omicron 变种在全球快速传播和致病性改变的基础。