Inactivated SARS-CoV-2 Variant Omicron, Lineage BQ.1.1 (USA/MD-HP38861/2022)

As of November 2022, the SARS-CoV-2 Omicron variants (B.1.1.529 and the BA lineage) are currently the only variants of concern (VOCs). At the end of November 2021, Omicron BA.1 rapidly overtook the previous VOC Delta. Shortly after the Omicron BA.1 lineage spread globally, Omicron BA.2 became the dominant strain globally. Subsequently, multiple descendants of BA.2, such as BA.5 and BA.2.75, emerged and became dominant in certain regions. Since its emergence, Omicron BA.2 has diversified significantly and transformed into other Omicron subvariants, including the most recently emerged variants.

Although both BA.5 and BA.2.75 diverged from BA.2, these two Omicron subvariants are phylogenetically independent, indicating that BA.5 and BA.2.75 arose independently. Recent studies have shown that the spike (S) proteins of these two variants exhibit similar evolutionary patterns: one pattern of amino acid substitutions that evade humoral immunity, and the other pattern of amino acid substitutions that increase binding affinity for human angiotensin-converting enzyme 2 (ACE2), the receptor for SARS-CoV-2 infection. In BA.5, the F486V substitution contributes to humoral immunity evasion, while the L452R substitution increases ACE2 binding affinity. In BA.2.75, the G446S substitution is responsible for humoral immunity evasion, while the N460K substitution increases ACE2 binding affinity. BQ.1.1, a descendant of BA.5, contains all five recent convergent substitutions (R346T, K444T, L452R, N460K, or F486V). BQ.1.1 was more effective than BA.5 in evading breakthrough infection sera from BA.2 and BA.5, as confirmed by neutralization assays. BQ.1.1 was less pathogenic than BA.5 in hamsters.