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

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 () and Haipeng Xiao ()
Additional contact information
Ji Wang: 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
Min Liu: The First Affiliated Hospital, Sun Yat-sen University
Sui Peng: The First Affiliated Hospital, Sun Yat-sen University
Haipeng Xiao: The First Affiliated Hospital, Sun Yat-sen University

Nature Communications, 2022, vol. 13, issue 1, 1-11

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-34633-7

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