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

• 成果类型: Article
• 署名作者: Jian, Fanchong; Wang, Jing; Yisimayi, Ayijiang; Song, Weiliang; Xu, Yanli; Chen, Xiaosu; Niu, Xiao; Yang, Sijie; Yu, Yuanling; Wang, Peng; Sun, Haiyan; Yu, Lingling; Wang, Jing; Wang, Yao; An, Ran; Wang, Wenjing; Ma, Miaomiao; Xiao, Tianhe; Gu, Qingqing; Shao, Fei; Wang, Youchun; Shen, Zhongyang; Jin, Ronghua; Cao, Yunlong
• 署名单位: Peking University; Changping Laboratory; Peking University; Peking University; Capital Medical University; Nankai University; Tsinghua University; Peking University; National Institute of Biological Sciences, Beijing; Chinese Academy of Medical Sciences - Peking Union Medical College; Peking Union Medical College; Institute of Medical Biology - CAMS; Nankai University
• 刊物名称: Nature
• ISSN/ISSBN: 0028-2693
• DOI: 10.1038/s41586-024-08315-x
• 发表日期: 2025-01-23
• 关键词: binding; evasion; escape

摘要

The continuous evolution of SARS-CoV-2, particularly the emergence of the BA.2.86/JN.1 lineage replacing XBB, necessitates re-evaluation of vaccine compositions1, 2-3. 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 show that infection with JN.1 elicits superior plasma neutralization against its subvariants. We highlight the strong immune evasion and receptor-binding capability of KP.3, supporting its foreseeable prevalence. Extensive analysis of the B cell receptor repertoire, in which we isolate approximately 2,000 receptor-binding-domain-specific antibodies, with targeting epitopes characterized by deep mutational scanning, underscores the superiority of JN.1-elicited memory B cells4,5. Class 1 IGHV3-53/3-66-derived neutralizing antibodies (NAbs) are important contributors to the wild-type reactivity of NAbs against JN.1. However, KP.2 and KP.3 evade a substantial subset of these antibodies, even those induced by JN.1, supporting a need for booster updates. JN.1-induced Omicron-specific antibodies also demonstrate high potency across Omicron. Escape hotspots for these NAbs have already been mutated, resulting in a higher immune barrier to escape and indicating probable recovery of escaped NAbs. In addition, the prevalence of IGHV3-53/3-66-derived antibodies and their ability to compete with all Omicron-specific NAbs suggests that they have an inhibitory effect on the activation of Omicron-specific naive B cells, potentially explaining the heavy immune imprinting in mRNA-vaccinated individuals6, 7-8. These findings delineate the evolving antibody response to the antigenic shift of Omicron from XBB to JN.1 and highlight the importance of developing the JN.1 lineage, especially KP.2- and KP.3-based vaccine boosters.