Neutralization sensitivity of the SARS-CoV-2 Omicron BA.2.75 sublineage

Abstract

The recently emerged BA.2.75 Omicron sublineage of SARS-CoV-2 identified in numerous countries is rapidly increasing in prevalence in regions of India. Compared with BA.2, the spike protein of BA.2.75 differs in nine amino acid residues. To determine the impact of the spike mutations on polyclonal and monoclonal antibody activity, we investigated the neutralization sensitivity of BA.2.75 in comparison with B.1, BA.2, BA.2.12.1, and BA.4/5. Analysis of post-boost samples from 30 vaccinated individuals revealed significantly lower serum neutralizing activity against BA.2.75 than against BA.2. However, BA.2.75 was more sensitive to serum neutralization than the widely circulating BA.4/5 sublineages. Moreover, evaluation of 17 clinical-stage monoclonal antibodies demonstrated individual differences in Omicron sublineage activity. Notably, some authorized antibodies with low activity against other Omicron sublineages demonstrated high BA.2.75 neutralizing potency. Our results indicate a less pronounced degree of antibody evasion of BA.2.75 compared with BA.4/5 and suggest that factors beyond immune evasion may be required for an expansion of BA.2.75 over BA.4/5.