Antibody evasion and receptor binding of SARS-CoV-2 LP.8.1.1, NB.1.8.1, XFG, and related subvariants

SARS-CoV-2 continues to evolve, causing waves of infections. It is critical to understand the features of the virus that explain its growth advantages. Recently, SARS-CoV-2 Omicron JN.1 subvariants KP.3.1.1 and XEC were outcompeted by LP.8.1 and LP.8.1.1. Other subvariants, including LF.7.2.1 and MC.10.1, were also under monitoring. Subsequently, NB.1.8.1 and XFG became dominant. We found that serum neutralizing antibody titers against LP.8.1, LP.8.1.1, LF.7, LF.7.2.1, and MC.10.1 were similar to XEC in 40 adults, including KP.2 monovalent mRNA vaccine recipients. NB.1.8.1 and XFG were more evasive of serum neutralization than LP.8.1.1. Neutralization by 12 monoclonal antibodies (mAbs) revealed that LP.8.1 and XFG, MC.10.1 and NB.1.8.1, and LF.7.2.1 evade different mAb classes. Lastly, the receptor-binding affinity of LP.8.1 was the highest among the tested viruses. Unlike most prior SARS-CoV-2 sublineage evolutionary trajectories, receptor-binding affinity better explained the rise of LP.8.1, while expansion of NB.1.8.1 and XFG appears correlated with enhanced antibody evasion.