Enhanced neutralization resistance of SARS-CoV-2 Omicron subvariants BQ.1, BQ.1.1, BA.4.6, BF.7, and BA.2.75.2

The continued evolution of SARS-CoV-2 has led to the emergence of several new Omicron subvariants, including BQ.1, BQ.1.1, BA.4.6, BF.7, and BA.2.75.2. Here, we examine the neutralization resistance of these subvariants against sera from 3-dose vaccinated healthcare workers, hospitalized BA.1-wave patients, and BA.4/5-wave patients. We found enhanced neutralization resistance in all new subvariants, especially in the BQ.1 and BQ.1.1 subvariants driven by N460K and K444T mutations, as well as the BA.2.75.2 subvariant driven largely by its F486S mutation. All Omicron subvariants maintained their weakened infectivity in Calu-3 cells, with the F486S mutation driving further diminished titer for the BA.2.75.2 subvariant. Molecular modeling revealed the mechanisms of antibody-mediated immune evasion by R346T, K444T, F486S, and D1199N mutations. Altogether, these findings shed light on the evolution of newly emerging SARS-CoV-2 Omicron subvariants. [Display omitted] •Enhanced neutralization resistance of BQ.1 and BQ.1.1 is driven by N460K and K444T•Enhanced neutralization resistance of BA.2.75.2 is driven by F486S•R346T and K444T contribute to evasion of class III antibody recognition•Modeling reveals that F486S reduces binding for both ACE2 and class I and II antibodies Numerous Omicron subvariants have emerged following BA.4/5 and BA.2.75 subvariants. Qu and colleagues investigate the neutralizing antibody resistance of these subvariants and their ancestral variants. BQ.1, BQ.1.1, BA.4.6, BF.7, and BA.2.75.2 exhibit enhanced neutralizing antibody escape, with BQ.1/BQ.1.1 and BA.2.75.2 driven by N460K/K444T and F486S mutations, respectively.