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

作者：Ian A. Mellis, Madeline Wu, Hsiang Hong, Chih-Chen Tzang, Anthony Bowen, Qian Wang, Carmen Gherasim, Virginia Pierce, Jayesh Shah, Lawrence J. Purpura, Michael T. Yin, Aubree Gordon, Yicheng Guo, David D. Ho · 发表于：bioRxiv (Cold Spring Harbor Laboratory) · 年份：2025 · DOI：10.1101/2025.07.18.662329 · 被引用次数：8 · 研究领域：Monoclonal and Polyclonal Antibodies Research、SARS-CoV-2 and COVID-19 Research、Advanced Biosensing Techniques and Applications

Abstract SARS-CoV-2 continues to evolve, causing repeated waves of infections around the world. It is critical to understand the features of the virus that explain its growth advantages. Recently, the SARS-CoV-2 Omicron JN.1 subvariants KP.3.1.1 and XEC were outcompeted by later JN.1 progenies, most prominently LP.8.1 and LP.8.1.1. Other recent JN.1 subvariants, such as LF.7.2.1, which became prevalent in Asia, and MC.10.1, have also been under monitoring. Subsequently, NB.1.8.1 and XFG subvariants began increasing in prevalence, as well. We found that serum neutralizing antibody titers against LP.8.1, LP.8.1.1, LF.7, LF.7.2.1, MC.10.1 were similar to XEC in a cohort of 20 KP.2-based monovalent mRNA vaccine (KP.2 MV) recipients and in a cohort 20 adults who did not receive KP.2 MV. NB.1.8.1 and XFG were more evasive of serum neutralization than LP.8.1.1. We then characterized subvariant susceptibility to monoclonal antibody (mAb) neutralization using a panel of 12 mAbs spanning several epitopes on the SARS-CoV-2 spike, and found that LP.8.1 and XFG, MC.10.1 and NB.1.8.1, and LF.7.2.1 evade different classes of mAbs relative to earlier JN.1 subvariants, even if the tested polyclonal serum neutralizing antibody titers were not different overall. Next, we found that the receptor-binding affinity of LP.8.1 to ACE2 was the highest among the tested viruses, while that of LF.7.2.1 was lowest. Therefore, unlike most prior SARS-CoV-2 sublineage evolutionary trajectories, receptor-bind...