Immune Evasion, Infectivity, and Fusogenicity of SARS-CoV-2 BA.2.86 and FLip Variants

Authors

Panke Qu
Kai Xu
Julia N Faraone
Negin Goodarzi
Yi-Min Zheng
Claire Carlin
Joseph S Bednash
Jeffrey C Horowitz
Rama K Mallampalli
Linda J Saif
Eugene M Oltz
Daniel Jones
Richard J Gumina
Shan-Lu Liu

Publication Date

2-1-2024

Journal

Cell

Abstract

Evolution of SARS-CoV-2 requires the reassessment of current vaccine measures. Here, we characterized BA.2.86 and XBB-derived variant FLip by investigating their neutralization alongside D614G, BA.1, BA.2, BA.4/5, XBB.1.5, and EG.5.1 by sera from 3-dose-vaccinated and bivalent-vaccinated healthcare workers, XBB.1.5-wave-infected first responders, and monoclonal antibody (mAb) S309. We assessed the biology of the variant spikes by measuring viral infectivity and membrane fusogenicity. BA.2.86 is less immune evasive compared to FLip and other XBB variants, consistent with antigenic distances. Importantly, distinct from XBB variants, mAb S309 was unable to neutralize BA.2.86, likely due to a D339H mutation based on modeling. BA.2.86 had relatively high fusogenicity and infectivity in CaLu-3 cells but low fusion and infectivity in 293T-ACE2 cells compared to some XBB variants, suggesting a potentially different conformational stability of BA.2.86 spike. Overall, our study underscores the importance of SARS-CoV-2 variant surveillance and the need for updated COVID-19 vaccines.

Keywords

Humans, Antibodies, Monoclonal, Antibodies, Neutralizing, Antibodies, Viral, COVID-19, COVID-19 Vaccines, Immune Evasion, SARS-CoV-2

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Associated Data

PMID: 38194968