摘要:SummarySARS-CoV-2 Omicron is the first pandemic variant of concern exhibiting an abrupt accumulation of mutations particularly in the receptor-binding domain that is a critical target of vaccination induced and therapeutic antibodies. Omicron's mutations did only marginally affect the binding of ACE2, and the two antibodies Sotrovimab and CR3022 but strongly impaired the binding of Casirivimab and Imdevimab. Moreover, as compared with Wuhan, there is reduced serum reactivity and a pronounced loss of competitive surrogate virus neutralization (sVN) against Omicron in naïve vaccinees and in COVID-19 convalescents after infection and subsequent vaccination. Finally, although the booster vaccination response conferred higher titers and better sVN, the effect was nonetheless significantly lower compared with responses against Wuhan. Overall, our data suggest that the antigenicity of Omicrons receptor binding motive has largely changed but antibodies such as Sotrovimab targeting other conserved sites maintain binding and therefore hold potential in prophylaxis and treatment of Omicron-induced COVID-19.Graphical abstractDisplay OmittedHighlights•Receptor binding motif antibodies Casirivimab and Imdevimab lose binding to Omicron•Binding of Sotrovimab and CR3022 is less affected by Omicrons mutations•IgG serum reactivity and competitive surrogate neutralization of Omicron are reduced•Loss of serum binding is accompanied by a pronounced loss of ACE2 competitionHealth sciences; Medicine; Immunology; Biological sciences