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A fourth dose of the inactivated SARS-CoV-2 vaccine redistributes humoral immunity to the N-terminal domain

Author

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  • Ji Wang

    (The First Affiliated Hospital, Sun Yat-sen University
    The First Affiliated Hospital, Sun Yat-sen University)

  • Caiguangxi Deng

    (The First Affiliated Hospital, Sun Yat-sen University)

  • Ming Liu

    (The First Affiliated Hospital, Sun Yat-sen University)

  • Yihao Liu

    (Clinical Trials Unit, The First Affiliated Hospital, Sun Yat-sen University)

  • Liubing Li

    (The First Affiliated Hospital, Sun Yat-sen University)

  • Zhangping Huang

    (The First Affiliated Hospital, Sun Yat-sen University)

  • Liru Shang

    (The First Affiliated Hospital, Sun Yat-sen University)

  • Juan Jiang

    (The First Affiliated Hospital, Sun Yat-sen University)

  • Yongyong Li

    (The First Affiliated Hospital, Sun Yat-sen University)

  • Ruohui Mo

    (Clinical Trials Unit, The First Affiliated Hospital, Sun Yat-sen University)

  • Hui Zhang

    (The First Affiliated Hospital, Sun Yat-sen University
    The First Affiliated Hospital, Sun Yat-sen University)

  • Min Liu

    (The First Affiliated Hospital, Sun Yat-sen University)

  • Sui Peng

    (The First Affiliated Hospital, Sun Yat-sen University
    Clinical Trials Unit, The First Affiliated Hospital, Sun Yat-sen University)

  • Haipeng Xiao

    (The First Affiliated Hospital, Sun Yat-sen University)

Abstract

The effectiveness of a 3rd dose of SARS-CoV-2 vaccines waned quickly in the Omicron-predominant period. In response to fast-waning immunity and the threat of Omicron variant of concern (VOC) to healthcare workers (HCWs), we conduct a non-randomized trial (ChiCTR2200055564) in which 38 HCWs volunteer to receive a homologous booster of inactivated vaccines (BBIBP-CorV) 6 months after the 3rd dose. The primary and secondary outcomes are neutralizing antibodies (NAbs) and the receptor-binding domain (RBD)-directed antibodies, respectively. The 4th dose recalls waned immunity while having distinct effects on humoral responses to different antigens. The peak antibody response to the RBD induced by the 4th dose is inferior to that after the 3rd dose, whereas responses to the N-terminal domain (NTD) of spike protein are further strengthened significantly. Accordingly, the 4th dose further elevates the peak level of NAbs against ancestral SARS-CoV-2 and Omicron BA.2, but not BA.1 which has more NTD mutations. No severe adverse events related to vaccination are recorded during the trial. Here, we show that redistribution of immune focus after repeated vaccinations may modulate cross-protective immune responses against different VOCs.

Suggested Citation

  • Ji Wang & Caiguangxi Deng & Ming Liu & Yihao Liu & Liubing Li & Zhangping Huang & Liru Shang & Juan Jiang & Yongyong Li & Ruohui Mo & Hui Zhang & Min Liu & Sui Peng & Haipeng Xiao, 2022. "A fourth dose of the inactivated SARS-CoV-2 vaccine redistributes humoral immunity to the N-terminal domain," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34633-7
    DOI: 10.1038/s41467-022-34633-7
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