Antibody potency, effector function, and combinations in protection and therapy for SARS-CoV-2 infection in vivo

J Exp Med. 2021 Mar 1;218(3):e20201993. doi: 10.1084/jem.20201993.

Abstract

SARS-CoV-2, the causative agent of COVID-19, has been responsible for over 42 million infections and 1 million deaths since its emergence in December 2019. There are few therapeutic options and no approved vaccines. Here, we examine the properties of highly potent human monoclonal antibodies (hu-mAbs) in a Syrian hamster model of SARS-CoV-2 and in a mouse-adapted model of SARS-CoV-2 infection (SARS-CoV-2 MA). Antibody combinations were effective for prevention and in therapy when administered early. However, in vitro antibody neutralization potency did not uniformly correlate with in vivo protection, and some hu-mAbs were more protective in combination in vivo. Analysis of antibody Fc regions revealed that binding to activating Fc receptors contributes to optimal protection against SARS-CoV-2 MA. The data indicate that intact effector function can affect hu-mAb protective activity and that in vivo testing is required to establish optimal hu-mAb combinations for COVID-19 prevention.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Murine-Derived* / immunology
  • Antibodies, Monoclonal, Murine-Derived* / pharmacology
  • Antibodies, Neutralizing* / immunology
  • Antibodies, Neutralizing* / pharmacology
  • Antibodies, Viral* / immunology
  • Antibodies, Viral* / pharmacology
  • Betacoronavirus / immunology*
  • COVID-19
  • Cell Line
  • Coronavirus Infections* / immunology
  • Coronavirus Infections* / therapy
  • Female
  • Humans
  • Mesocricetus
  • Mice
  • Mice, Inbred BALB C
  • Pandemics*
  • Pneumonia, Viral* / immunology
  • Pneumonia, Viral* / therapy
  • SARS-CoV-2

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Antibodies, Neutralizing
  • Antibodies, Viral