Characterization of RBD-specific cross-neutralizing antibodies responses against SARS-CoV-2 variants from COVID-19 convalescents

Front Immunol. 2023 May 10:14:1160283. doi: 10.3389/fimmu.2023.1160283. eCollection 2023.

Abstract

Introduction: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been posing a severe threat to global public health. Although broadly neutralizing antibodies have been used to prevent or treat corona virus disease 2019 (COVID-19), new emerging variants have been proven resistant to these antibodies.

Methods: In this study, we isolated receptor binding domain (RBD)-specific memory B cells using single-cell sorting method from two COVID-19 convalescents and expressed the antibody to test their neutralizing activity against diverse SARS-CoV-2 variants. Then, we resolved antibody-RBD complex structures of potent RBD-specific neutralizing antibodies by X-ray diffraction method. Finally, we analyzed the whole antibody repertoires of the two donors and studied the evolutionary pathway of potent neutralizing antibodies.

Results and discussion: We identified three potent RBD-specific neutralizing antibodies (1D7, 3G10 and 3C11) from two COVID-19 convalescents that neutralized authentic SARS-CoV-2 WH-1 and Delta variant, and one of them, 1D7, presented broadly neutralizing activity against WH-1, Beta, Gamma, Delta and Omicron authentic viruses. The resolved antibody-RBD complex structures of two antibodies, 3G10 and 3C11, indicate that both of them interact with the external subdomain of the RBD and that they belong to the RBD-1 and RBD-4 communities, respectively. From the antibody repertoire analysis, we found that the CDR3 frequencies of the light chain, which shared high degrees of amino acid identity with these three antibodies, were higher than those of the heavy chain. This research will contribute to the development of RBD-specific antibody-based drugs and immunogens against multiple variants.

Keywords: SARS-CoV-2; antibody-antigen complex; antibodyome; neutralizing antibody; receptor binding domain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Neutralizing
  • Broadly Neutralizing Antibodies
  • COVID-19*
  • Humans
  • SARS-CoV-2*

Substances

  • Broadly Neutralizing Antibodies
  • Antibodies, Neutralizing

Supplementary concepts

  • SARS-CoV-2 variants

Grants and funding

This study was supported by grants from the Beijing Municipal Natural Science Foundation (M21015), the National Medical Center for Infectious Diseases B2022011-3(2020), The First Affiliated Hospital, Zhejiang University School of Medicine, State Key Laboratory of Infectious Disease Prevention and Control Grant(2021SKLID304), the Queensland-Chinese Academy of Sciences Collaborative Science Fund 2020 (153211KYSB20200001), the Special Program of China National Tobacco Corporation(110202102034), and the National Key Research and Development Program of China (2021YFF0700305). The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.