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 Widen, Brian R. Mann, Rebecca Kondor, C. Todd Davis, Bin Zhou, David E. Wentworth, Xuping Xie, Pei-Yong Shi

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


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.

Original languageEnglish (US)
Article numbere2161422
Pages (from-to)e2161422
JournalEmerging Microbes and Infections
Issue number1
StatePublished - Dec 2023


  • SARS-CoV-2
  • antigenicity
  • neutralization
  • variants
  • viral fitness

ASJC Scopus subject areas

  • Epidemiology
  • Parasitology
  • Microbiology
  • Immunology
  • Drug Discovery
  • Infectious Diseases
  • Virology


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