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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Viral Immunology
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1440819
This article is part of the Research Topic Treatment for COVID-19 across the possible use of monoclonal antibodies and antiviral agents: clinical, epidemiological, virological, and immunological aspects View all 5 articles

Individuals Carrying the HLA-B*15 Allele Exhibit Favorable Responses to COVID-19 Vaccines but are More Susceptible to Omicron BA.5.2 and XBB.1.16 Infection

Provisionally accepted
Lingxin Meng Lingxin Meng 1Yue Pan Yue Pan 1Yueping Liu Yueping Liu 2Rui He Rui He 1Yuting Sun Yuting Sun 1Chenhui Wang Chenhui Wang 3Lei Fei Lei Fei 1Airu Zhu Airu Zhu 1Zhongfang Wang Zhongfang Wang 4Yunfei An Yunfei An 5Yuzhang Wu Yuzhang Wu 1Bo Diao Bo Diao 1Yongwen Chen Yongwen Chen 1*
  • 1 Institute of Immunology, Third Military Medical University, Chongqing, China
  • 2 Department of Medical Laboratory Center, General Hospital of Central Theater Command, Wuhan, Hebei Province, China
  • 3 Beijing Institute of Microbiology and Epidemiology, Beijing, Beijing Municipality, China
  • 4 State Key Laboratory of Infectious Disease Prevention and Control, Chinese Center for Disease Control and Prevention, Beijing, Beijing Municipality, China
  • 5 Department of Rheumatology & Immunology, Children's Hospital of Chongqing Medical University, Chongqing, China

The final, formatted version of the article will be published soon.

    CoV-2 invasion, nevertheless, Omicron variants still successfully cause breakthrough infection, and the underlying mechanisms are poorly understood.. Sequential blood samples were continuously collected at different time points from 252 volunteers who were received the CanSino Ad5-nCoV (n= 183) vaccine or the Sinovac CoronaVac inactivated vaccine (n= 69). The anti-SARS-CoV-2 prototype and Omicron BA.5.2 as well as XBB.1.16 variant neutralizing antibodies (Nab) in sera were detected by ELISA. Sera were also used to measure pseudo and live virus neutralization assay. The associations between the anti-prototype Nab levels and different HLA-ABC alleles were analyzed using artificial intelligence (AI)-deep learning techniques. The frequency of B cells in PBMCs was investigated by flow cytometry assay (FACs). Results. Individuals carrying the HLA-B * 15 allele manifested the highest concentrations of anti-SARS-CoV-2 prototype Nab after vax administration. Unfortunately, these volunteers are more susceptible to Omicron BA.5.2 breakthrough infection due to their sera have poorer anti-BA.5.2 Nab and lower levels of viral neutralization efficacy. FACs confirmed that a significant decrease in CD19 + CD27 + RBD + memory B cells in these HLA-B * 15 population compared to other cohorts. Importantly, generating lower concentrations of cross-reactive anti-XBB.1.16 Nab post-BA.5.2 infection caused HLA-B * 15 individuals to be further infected by XBB.1.16 variant. Conclusions. Individuals carrying the HLA-B * 15 allele respond better to COVID-19 vax including the CanSino Ad5-nCoV and the Sinovac CoronaVac inactivated vaccines, but are more susceptible to Omicron variant infection, thus, a novel vaccine against this population is necessary for COVID-19 pandemic control in the future.

    Keywords: COVID-19, Omicron Variants, HLA-B*15, Vaccination, SARS-CoV-2

    Received: 30 May 2024; Accepted: 19 Jul 2024.

    Copyright: © 2024 Meng, Pan, Liu, He, Sun, Wang, Fei, Zhu, Wang, An, Wu, Diao and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Yongwen Chen, Institute of Immunology, Third Military Medical University, Chongqing, China

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