Antibody Evasion Properties of SARS-CoV-2 Omicron Sublineages

The identification of the Omicron variant (B.1.1.529.1 or BA.1) of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) in Botswana in November 2021[1][1] immediately raised alarms due to the sheer number of mutations in the spike glycoprotein that could lead to striking antibody evasion. We[2][2] and others[3][3]–[6][4] recently reported results in this Journal confirming such a concern. Continuing surveillance of Omicron evolution has since revealed the rise in prevalence of two sublineages, BA.1 with an R346K mutation (BA.1+R346K) and B.1.1.529.2 (BA.2), with the latter containing 8 unique spike mutations while lacking 13 spike mutations found in BA.1. We therefore extended our studies to include antigenic characterization of these new sublineages. Polyclonal sera from patients infected by wild-type SARS-CoV-2 or recipients of current mRNA vaccines showed a substantial loss in neutralizing activity against both BA.1+R346K and BA.2, with drops comparable to that already reported for BA.1[2][2],[3][3],[5][5],[6][4]. These findings indicate that these three sublineages of Omicron are antigenically equidistant from the wild-type SARS-CoV-2 and thus similarly threaten the efficacies of current vaccines. BA.2 also exhibited marked resistance to 17 of 19 neutralizing monoclonal antibodies tested, including S309 (sotrovimab)[7][6], which had retained appreciable activity against BA.1 and BA.1+R346K[2][2]–[4][7],[6][4]. This new finding shows that no presently approved or authorized monoclonal antibody therapy could adequately cover all sublineages of the Omicron variant. ### Competing Interest Statement S.I, Lihong Liu, J.Y., Yaoxing Huang, and D.D.H. are inventors on patent applications (WO2021236998) or provisional patent applications (63/271,627) filed by Columbia University for a number of SARS-CoV-2 neutralizing antibodies described in this anuscript. Both sets of applications are under review. D.D.H. is a co-founder of TaiMed Biologics and RenBio, consultant to WuXi Biologics and Brii Biosciences, and board director for Vicarious Surgical. [1]: #ref-1 [2]: #ref-2 [3]: #ref-3 [4]: #ref-6 [5]: #ref-5 [6]: #ref-7 [7]: #ref-4