Distinct Patterns of SARS-CoV-2 BA.2.87.1 and JN.1 Variants in Immune Evasion, Antigenicity and Cell-Cell Fusion

Li, P.; Liu, Y.; Faraone, J.; Hsu, C. C.; Chamblee, M.; Zheng, Y.-M.; Carlin, C.; Bednash, J. S.; Horowitz, J. C.; Mallampalli, R. K.; Saif, L. J.; Oltz, E. M.; Jones, D.; Li, J.; Gumina, R. J.; Liu, S.-L.

doi:10.1101/2024.03.11.583978

bioRxiv · 10.1101/2024.03.11.583978

Distinct Patterns of SARS-CoV-2 BA.2.87.1 and JN.1 Variants in Immune Evasion, Antigenicity and Cell-Cell Fusion

Li, P.·Liu, Y.·Faraone, J.·Hsu, C. C.·Chamblee, M.·Zheng, Y.-M.·Carlin, C.·Bednash, J. S.·Horowitz, J. C.·Mallampalli, R. K.·Saif, L. J.·Oltz, E. M.·Jones, D.·Li, J.·Gumina, R. J.·Liu, S.-L.

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Abstract

The rapid evolution of SARS-CoV-2 variants presents a constant challenge to the global vaccination effort. In this study, we conducted a comprehensive investigation into two newly emerged variants, BA.2.87.1 and JN.1, focusing on their neutralization resistance, infectivity, antigenicity, cell-cell fusion, and spike processing. Neutralizing antibody (nAb) titers were assessed in diverse cohorts, including individuals who received a bivalent mRNA vaccine booster, patients infected during the BA.2.86/JN.1-wave, and hamsters vaccinated with XBB.1.5-monovalent vaccine. We found that BA.2.87.1 shows much less nAb escape from WT-BA.4/5 bivalent mRNA vaccination and JN.1-wave breakthrough infection sera compared to JN.1 and XBB.1.5. Interestingly. BA.2.87.1 is more resistant to neutralization by XBB.15-monovalent-vaccinated hamster sera than BA.2.86/JN.1 and XBB.1.5, but efficiently neutralized by a class III monoclonal antibody S309, which largely fails to neutralize BA.2.86/JN.1. Importantly, BA.2.87.1 exhibits higher levels of infectivity, cell-cell fusion activity, and furin cleavage efficiency than BA.2.86/JN.1. Antigenically, we found that BA.2.87.1 is closer to the ancestral BA.2 compared to other recently emerged Omicron subvariants including BA.2.86/JN.1 and XBB.1.5. Altogether, these results highlight immune escape properties as well as biology of new variants and underscore the importance of continuous surveillance and informed decision-making in the development of effective vaccines.

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Li, P., Liu, Y., Faraone, J., Hsu, C. C., Chamblee, M., Zheng, Y.-M., Carlin, C., Bednash, J. S., Horowitz, J. C., Mallampalli, R. K., Saif, L. J., Oltz, E. M., Jones, D., Li, J., Gumina, R. J., Liu, S.-L.. 2024-03-11. Distinct Patterns of SARS-CoV-2 BA.2.87.1 and JN.1 Variants in Immune Evasion, Antigenicity and Cell-Cell Fusion. https://doi.org/10.1101/2024.03.11.583978

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