Omicron Subvariants, Including BA.4 and BA.5, Substantially Preserve T Cell Epitopes of Ancestral SARS-CoV-2.

https://immunenetwork.org The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants (B.1.1.529 and related) that emerged in November 2021 have spread worldwide, and are designated a variant of concern by the World Health Organization (WHO) (1). They have become the dominant strains, comprising >99% of newly deposited SARS-CoV-2 sequences in GISIAD (www. gisaid.org) as of May 16, 2022 (2). Following the emergence of B.1.1.529 (BA.1), BA.2 (often called stealth Omicron) soon became the most prevalent sublineage worldwide. Subsequent subvariants, including BA.2.9, BA.2.12.1, BA.4, and BA.5, are now rapidly dominating the circulating Omicron subvariants in originating regions, and are beginning to spread globally (2). The dominance of Omicron variants and their rapid evolution into various subvariants have raised concerns regarding the effects of the immunity elicited by natural infection or vaccination. As evolution continues, the variants’ spike proteins exhibit higher affinities toward ACE2, and/ or increasing capacity for evading preformed neutralizing antibodies induced by previous natural infection or vaccination (3-5). These changes are consistent with increased breakthrough infections and re-infections with Omicron variants (6,7).