Antibody evasion properties of SARS-CoV-2 Omicron sublineages

The identification of the Omicron (B.1.1.529.1 or BA.1) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Botswana in November 2021(1) immediately caused concern owing to the number of alterations in the spike glycoprotein that could lead to antibody evasion. We(2) and others(3-6) recently reported results confirming such a concern. Continuing surveillance of the evolution of Omicron has since revealed the rise in prevalence of two sublineages, BA.1 with an R346K alteration (BA.1+R346K, also known as BA.1.1) and B.1.1.529.2 (BA.2), with the latter containing 8 unique spike alterations and lacking 13 spike alterations found in BA.1. Here we 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 (refs. (2,3,5,6)). 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), which had retained appreciable activity against BA.1 and BA.1+R346K (refs. (2-4,6)). This finding shows that no authorized monoclonal antibody therapy could adequately cover all sublineages of the Omicron variant, except for the recently authorized LY-CoV1404 (bebtelovimab).

Automated summary

The identification of the Omicron variant of SARS-CoV-2 in Botswana in November 2021 sparked concern due to the spike protein alterations that could potentially evade antibodies. Further studies showed that the Omicron sublineages, BA.1+R346K and BA.2, are antigenically similar to the wild-type virus and pose similar risks to the effectiveness of current vaccines. BA.2 also demonstrated resistance to many neutralizing monoclonal antibodies, highlighting the challenges in developing effective therapeutic options.