Cross-neutralization and viral fitness of SARS-CoV-2 Omicron sublineages

Abstract

The rapid evolution of SARS-CoV-2 Omicron sublineages mandates a better un-derstanding of viral replication and cross-neutralization among these sublineages. Here we used K18-hACE2 mice and primary human airway cultures to examine the viral fit-ness and antigenic relationship among Omicron sublineages. In both K18-hACE2 mice and human airway cultures, Omicron sublineages exhibited a replication order of BA.5 ≥ BA.2 ≥ BA.2.12.1 > BA.1; no difference in body weight loss was observed among differ-ent sublineage-infected mice. The BA.1-, BA.2-, BA.2.12.1-, and BA.5-infected mice de-veloped distinguisable cross-neutralizations against Omicron sublineages, but exhibited little neutralization against the index virus (i.e., USA-WA1/2020) or the Delta variant. Surprisingly, the BA.5-infected mice developed higher neutralization activity against heterologous BA.2 and BA.2.12.1 than that against homologous BA.5; serum neutralizing titers did not always correlate with viral replication levels in infected animals. Our results reveal distinct antigenic cartography of Omicron sublineages and support the bivalent vaccine approach.