Inactivated SARS-CoV-2 Variant Omicron, Lineage BA.2.12.1 (USA/NY-Wadsworth-22014351-01/2022)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron, or B.1.1.529, variant has dominated the COVID-19 pandemic. Globally, the BA.2 subvariant has rapidly replaced the previous BA.1 and BA.1.1 subvariants. The Omicron subvariant and its significant spread have raised concerns. BA.2.12.1 emerged in the United States in early February 2022 and has significantly spread, now accounting for over 55% of all new SARS-CoV-2 infections in the country. BA.4 and BA.5 emerged in South Africa in January 2022 and quickly became dominant, with a combined frequency exceeding 88%.

Phylogenetically, these new subvariants evolved independently of BA.2. The spike protein of BA.2.12.1 contains the L452Q and S704L mutations, in addition to the known mutations in BA.2. The spike proteins of BA.4 and BA.5 are identical, each with four mutations: Del69-70, L452R, F486V, and R493Q (a reversion mutation). BA.2.12.1 is only slightly more resistant than BA.2 (1.8-fold) to sera from vaccinated and boosted individuals. However, BA.4/5 are significantly more resistant than BA.2 (4.2-fold), making them more susceptible to vaccine-induced breakthrough infections. The mutation at spike residue L452, found in both BA.2.12.1 and BA.4/5, helps evade some antibodies that target the so-called class 2 and class 3 regions of the receptor-binding domain. The F486V mutation found in BA.4/5 helps evade certain class 1 and class 2 antibodies but reduces the spike''s affinity for the viral receptor. However, the R493Q back mutation restores receptor affinity, thereby restoring the fitness of BA.4/5.