Evolving antibody response to SARS-CoV-2 antigenic shift from XBB to JN.1

作者：Fanchong Jian, Jing Wang, Ayijiang Yisimayi, Weiliang Song, Yanli Xu, Xiaosu Chen, Xiao Niu, Sijie Yang, Yuanling Yu, Peng Wang, Haiyan Sun, Lingling Yu, Jing Wang, Yao Wang, Ran An, Wenjing Wang, Miaomiao Ma, Tianhe Xiao, Qingqing Gu, Fei Shao, Youchun Wang, Zhongyang Shen, Ronghua Jin, Yunlong Cao · 发表于：Nature · 年份：2024 · DOI：10.1038/s41586-024-08315-x · 被引用次数：150 · 研究领域：SARS-CoV-2 and COVID-19 Research、Monoclonal and Polyclonal Antibodies Research、vaccines and immunoinformatics approaches

The continuous evolution of SARS-CoV-2, particularly the emergence of BA.2.86/JN.1 lineage replacing XBB, necessitates re-evaluation of vaccine compositions 1–3 . Here, we provide a comprehensive analysis of the humoral immune response to XBB and JN.1 human exposure. We demonstrate the antigenic distinctiveness of XBB and JN.1 lineages in SARS-CoV-2-naive individuals, and JN.1 infection elicits superior plasma neutralization against its subvariants. We highlight KP.3’s strong immune evasion and receptor binding capability, supporting its foreseeable prevalence. Extensive analysis of the BCR repertoire, isolating ~2000 RBD-specific antibodies with their targeting epitopes characterized by deep mutational scanning (DMS), underscores the superiority of JN.1-elicited memory B cells 4,5 . Class 1 IGHV3-53/3-66-derived neutralizing antibodies (NAbs) contribute majorly within wildtype-reactive NAbs against JN.1. However, KP.2 and KP.3 evade a substantial subset, even those induced by JN.1, advocating for booster updates to KP.2/KP.3. JN.1-induced Omicron-specific antibodies also demonstrate high potency across Omicron. Escape hotspots of these NAbs have already been mutated, resulting in higher immune barrier to escape, considering probable recovery of escaped NAbs. Additionally, the prevalence of IGHV3-53/3-66-derived antibodies, and their capability of competing with all Omicron-specific NAbs suggests their inhibitory role on the activation of Omicron-specific naive B cells, poten...