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

Xia, H.; Yeung, J.; Kalveram, B.; Bills, C. J.; Chen, J. Y.-C.; Kurhade, C.; Zou, j.; Widen, S. G.; Mann, B. R.; Kondor, R. J.; Davis, T. C.; Zhou, B.; Wentworth, D. E.; Xie, X.; Shi, P.-Y.

doi:10.1101/2022.11.08.515725

bioRxiv · 10.1101/2022.11.08.515725

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

Xia, H.·Yeung, J.·Kalveram, B.·Bills, C. J.·Chen, J. Y.-C.·Kurhade, C.·Zou, j.·Widen, S. G.·Mann, B. R.·Kondor, R. J.·Davis, T. C.·Zhou, B.·Wentworth, D. E.·Xie, X.·Shi, P.-Y.

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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 distinguisable cross-neutralizations against Omicron sublineages, but exhibited little neutralizations 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 revealed a distinct antigenic cartography of Omicron sublineages and support the bivalent vaccine approach.

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Xia, H., Yeung, J., Kalveram, B., Bills, C. J., Chen, J. Y.-C., Kurhade, C., Zou, j., Widen, S. G., Mann, B. R., Kondor, R. J., Davis, T. C., Zhou, B., Wentworth, D. E., Xie, X., Shi, P.-Y.. 2022-11-09. Cross-neutralization and viral fitness of SARS-CoV-2 Omicron sublineages. https://doi.org/10.1101/2022.11.08.515725

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