Cross-neutralization and viral fitness of SARS-CoV-2 Omicron sublineages
Hongjie Xia, Jason Yeung, Birte Kalveram, Cody J. Bills, John Yun-Chung Chen, Chaitanya Kurhade, Jing Zou, Steven G. Widen, Brian R. Mann, Rebecca Kondor, C. Todd Davis, Bin Zhou, David E. Wentworth, Xuping Xie, Pei‐Yong Shi
Abstract
The rapid evolution of SARS-CoV-2 Omicron sublineages mandates a better understanding of viral replication and cross-neutralization among these sublineages. Here we used K18-hACE2 mice and primary human airway cultures to examine the viral fitness 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 different sublineage-infected mice. The BA.1-, BA.2-, BA.2.12.1-, and BA.5-infected mice developed distinguishable 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 titres did not always correlate with viral replication levels in infected animals. Our results revealed a distinct antigenic cartography of Omicron sublineages and support the bivalent vaccine approach.