Immune evasion, infectivity, and fusogenicity of SARS-CoV-2 BA.2.86 and FLip variants

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. [Display omitted] •BA.2.86 is less immune evasive compared to FLip and other XBB variants•BA.2.86 is antigenically more similar to BA.2 and BA.4/5 than XBB variants•MAb S309 is unable to neutralize BA.2.86 possibly contributed by a D339H mutation•The fusion and infectivity of BA.2.86 is higher than XBB variants in CaLu-3 cells The SARS-CoV-2 BA.2.86 variant is less resistant to neutralization by bivalent vaccine-induced antibodies compared to FLip and other XBB variants but more resistant to mAb S309. BA.2.86 shows higher fusogenicity and infectivity in CaLu-3 cells compared to that in 293T-ACE2 cells.