IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v637y2025i8047d10.1038_s41586-024-08315-x.html
   My bibliography  Save this article

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

Author

Listed:
  • Fanchong Jian

    (Peking University
    Changping Laboratory
    Peking University)

  • Jing Wang

    (Peking University
    Changping Laboratory
    Peking University)

  • Ayijiang Yisimayi

    (Peking University
    Changping Laboratory
    Peking University)

  • Weiliang Song

    (Peking University
    Changping Laboratory
    Peking University)

  • Yanli Xu

    (Capital Medical University)

  • Xiaosu Chen

    (Nankai University)

  • Xiao Niu

    (Peking University
    Peking University)

  • Sijie Yang

    (Peking University
    Tsinghua University)

  • Yuanling Yu

    (Changping Laboratory)

  • Peng Wang

    (Changping Laboratory)

  • Haiyan Sun

    (Changping Laboratory)

  • Lingling Yu

    (Changping Laboratory)

  • Jing Wang

    (Changping Laboratory)

  • Yao Wang

    (Changping Laboratory)

  • Ran An

    (Changping Laboratory)

  • Wenjing Wang

    (Changping Laboratory)

  • Miaomiao Ma

    (Changping Laboratory)

  • Tianhe Xiao

    (Peking University
    Peking University)

  • Qingqing Gu

    (Changping Laboratory)

  • Fei Shao

    (Changping Laboratory)

  • Youchun Wang

    (Changping Laboratory
    Chinese Academy of Medical Science & Peking Union Medical College)

  • Zhongyang Shen

    (Nankai University)

  • Ronghua Jin

    (Capital Medical University)

  • Yunlong Cao

    (Peking University
    Changping Laboratory
    Tsinghua University)

Abstract

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 compositions1–3. 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 individuals6–8. 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.

Suggested Citation

  • 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 & We, 2025. "Evolving antibody response to SARS-CoV-2 antigenic shift from XBB to JN.1," Nature, Nature, vol. 637(8047), pages 921-929, January.
  • Handle: RePEc:nat:nature:v:637:y:2025:i:8047:d:10.1038_s41586-024-08315-x
    DOI: 10.1038/s41586-024-08315-x
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41586-024-08315-x
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.

    File URL: https://libkey.io/10.1038/s41586-024-08315-x?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:637:y:2025:i:8047:d:10.1038_s41586-024-08315-x. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.