Therapeutic effect of CT-P59 against SARS-CoV-2 South African variant

Biochem Biophys Res Commun. 2021 Aug 20:566:135-140. doi: 10.1016/j.bbrc.2021.06.016. Epub 2021 Jun 7.

Abstract

The global circulation of newly emerging variants of SARS-CoV-2 is a new threat to public health due to their increased transmissibility and immune evasion. Moreover, currently available vaccines and therapeutic antibodies were shown to be less effective against new variants, in particular, the South African (SA) variant, termed 501Y.V2 or B.1.351. To assess the efficacy of the CT-P59 monoclonal antibody against the SA variant, we sought to perform as in vitro binding and neutralization assays, and in vivo animal studies. CT-P59 neutralized B.1.1.7 variant to a similar extent as to wild type virus. CT-P59 showed reduced binding affinity against a RBD (receptor binding domain) triple mutant containing mutations defining B.1.351 (K417N/E484K/N501Y) also showed reduced potency against the SA variant in live virus and pseudovirus neutralization assay systems. However, in vivo ferret challenge studies demonstrated that a therapeutic dosage of CT-P59 was able to decrease B.1.351 viral load in the upper and lower respiratory tracts, comparable to that observed for the wild type virus. Overall, although CT-P59 showed reduced in vitro neutralizing activity against the SA variant, sufficient antiviral effect in B.1.351-infected animals was confirmed with a clinical dosage of CT-P59, suggesting that CT-P59 has therapeutic potential for COVID-19 patients infected with SA variant.

Keywords: B.1.351; CT-P59; Regdanvimab; SARS-CoV-2 virus; Therapeutic antibody; Variant.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Humanized / immunology
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antibodies, Neutralizing / immunology
  • Antibodies, Neutralizing / therapeutic use*
  • Antibodies, Viral / immunology
  • Antibodies, Viral / therapeutic use*
  • COVID-19 / immunology
  • COVID-19 / therapy*
  • COVID-19 / virology*
  • Disease Models, Animal
  • Female
  • Ferrets
  • Humans
  • Immunoglobulin G / immunology
  • Immunoglobulin G / therapeutic use*
  • In Vitro Techniques
  • Neutralization Tests
  • Pandemics
  • SARS-CoV-2* / genetics
  • SARS-CoV-2* / immunology
  • SARS-CoV-2* / pathogenicity
  • South Africa
  • Viral Load / immunology

Substances

  • Antibodies, Monoclonal, Humanized
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Immunoglobulin G
  • regdanvimab