Development and characterization of SARS-CoV-2 variant-neutralizing monoclonal antibodies

Antiviral Res. 2021 Dec:196:105206. doi: 10.1016/j.antiviral.2021.105206. Epub 2021 Nov 8.

Abstract

Vaccination and administration of monoclonal antibody cocktails are effective tools to control the progression of infectious diseases and to terminate pandemics such as COVID-19. However, the emergence of SARS-CoV-2 mutants with enhanced transmissibility and altered antigenicity requires broad-spectrum therapies. Here we developed a panel of SARS-CoV-2 specific mouse monoclonal antibodies (mAbs), and characterized them based on ELISA, Western immunoblot, isotyping, and virus neutralization. Six neutralizing mAbs that exhibited high-affinity binding to SARS-CoV-2 spike protein were identified, and their amino acid sequences were determined by mass spectrometry. Functional assays confirmed that three mAbs, F461G11, F461G15, and F461G16 neutralized four variants of concern (VOC): B.1.1.7 (alpha), B.1.351 (beta), P.1 (gamma) and B.1.617.2 (delta) These mAbs are promising candidates for COVID-19 therapy, and understanding their interactions with virus spike protein should support further vaccine and antibody development.

Keywords: Broad-spectrum neutralizing mAbs; PRNT; SARS-CoV-2; Variant of concern (VOC).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Neutralizing* / immunology
  • Antibodies, Neutralizing* / therapeutic use
  • Antibodies, Viral / immunology
  • COVID-19* / immunology
  • COVID-19* / prevention & control
  • Hemolytic Plaque Technique
  • Humans
  • Mice
  • SARS-CoV-2* / immunology
  • Spike Glycoprotein, Coronavirus / immunology*

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2

Supplementary concepts

  • SARS-CoV-2 variants