Convalescent human IgG, but not IgM, from COVID-19 survivors confers dose-dependent protection against SARS-CoV-2 replication and disease in hamsters

Front Immunol. 2023 Mar 21:14:1138629. doi: 10.3389/fimmu.2023.1138629. eCollection 2023.

Abstract

Introduction: Antibody therapeutic strategies have served an important role during the COVID-19 pandemic, even as their effectiveness has waned with the emergence of escape variants. Here we sought to determine the concentration of convalescent immunoglobulin required to protect against disease from SARS-CoV-2 in a Syrian golden hamster model.

Methods: Total IgG and IgM were isolated from plasma of SARS-CoV-2 convalescent donors. Dose titrations of IgG and IgM were infused into hamsters 1 day prior to challenge with SARS-CoV-2 Wuhan-1.

Results: The IgM preparation was found to have ~25-fold greater neutralization potency than IgG. IgG infusion protected hamsters from disease in a dose-dependent manner, with detectable serum neutralizing titers correlating with protection. Despite a higher in vitro neutralizing potency, IgM failed to protect against disease when transferred into hamsters.

Discussion: This study adds to the growing body of literature that demonstrates neutralizing IgG antibodies are important for protection from SARS-CoV-2 disease, and confirms that polyclonal IgG in sera can be an effective preventative strategy if the neutralizing titers are sufficiently high. In the context of new variants, against which existing vaccines or monoclonal antibodies have reduced efficacy, sera from individuals who have recovered from infection with the emerging variant may potentially remain an efficacious tool.

Keywords: IgG; IgM; SARS-CoV-2; antibody; hamster; passive transfer.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antibodies, Neutralizing
  • COVID-19*
  • Cricetinae
  • Humans
  • Immunoglobulin G
  • Mesocricetus
  • Pandemics
  • SARS-CoV-2*
  • Survivors

Substances

  • Immunoglobulin G
  • Antibodies, Neutralizing

Grants and funding

We acknowledge support from the U.S. Department of Defense, Defense Health Agency (Restoral FY20). This work was also partially executed through a cooperative agreement between the U.S. Department of Defense and the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. (W81XWH-18-2-0040). The views, opinions and/or findings are those of the authors and should not be construed to represent the positions, policy or decision of the U.S. Army or the Department of Defense.