Immune evasion, infectivity, and membrane fusion of the SARS-CoV-2 JN.1 variant.

Abstract

SARS-CoV-2 undergoes continuous mutations during transmission, resulting in a variety of Omicron subvariants. Currently, SARS-CoV-2 BA.2.86 and its descendants JN.1, KP.2, KP.1.1 have been identified as the primary variants spreading globally. These emerging Omicron variants have increased transmissibility, potentially elevating the risk of viral reinfection in the population. However, the biological characteristics of newly-emerged Omicron subvariants in infecting host cells remain unclear. In this study, we assessed the neutralization effect of BA.2.86 and its descendant JN.1, as well as D614G, BA.2, BA.4/5, XBB.1.5, EG.5.1, HV.1, HK.3, JD.1.1 and JG.3 on convalescent sera obtained from individuals infected with BA.5 or XBB.1.5 strain. We evaluated the biological characteristics of variants spike proteins by measuring viral infectivity, affinity for receptors, and membrane fusion. Compared to XBB-related subvariants, BA.2.86 exhibited a diminished immune escape response, but JN.1 displayed a markedly augmented immune escape capability, which was closely related to its rapid transmission. BA.2.86 was less infectious in susceptible cells, while the JN.1 variant exhibited relatively high infectivity. Notably, BA.2.86 and JN.1 exhibited low fusion activity in 293 T-ACE2 cells, but relatively high fusogenicity in transmembrane protease serine 2 (TMPRSS2) overexpression cells. This study explored the evolutionary characteristics of emerging Omicron subvariants in host adaptation, and provided new strategies for the prevention and treatment of coronavirus disease 2019 (COVID-19).