Evaluation of Cellular and Serological Responses to Acute SARS-CoV-2 Infection Demonstrates the Functional Importance of the Receptor-Binding Domain

J Immunol. 2021 Jun 1;206(11):2605-2613. doi: 10.4049/jimmunol.2001420. Epub 2021 May 5.


The factors that control the development of an effective immune response to the recently emerged SARS-CoV-2 virus are poorly understood. In this study, we provide a cross-sectional analysis of the dynamics of B cell responses to SARS-CoV-2 infection in hospitalized COVID-19 patients. We observe changes in B cell subsets consistent with a robust humoral immune response, including significant expansion of plasmablasts and activated receptor-binding domain (RBD)-specific memory B cell populations. We observe elevated titers of Abs to SARS-CoV-2 RBD, full-length Spike, and nucleoprotein over the course of infection, with higher levels of RBD-specific IgG correlating with increased serum neutralization. Depletion of RBD-specific Abs from serum removed a major portion of neutralizing activity in most individuals. Some donors did retain significant residual neutralization activity, suggesting a potential Ab subset targeting non-RBD epitopes. Taken together, these findings are instructive for future vaccine design and mAb strategies.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • B-Lymphocytes / immunology*
  • COVID-19 / immunology*
  • Cell Line
  • Female
  • Humans
  • Immunity, Cellular*
  • Immunologic Memory*
  • Male
  • Nucleocapsid Proteins / immunology*
  • Protein Domains
  • SARS-CoV-2 / immunology*
  • Spike Glycoprotein, Coronavirus / immunology*


  • Nucleocapsid Proteins
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2