4.6 Article

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

Journal

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2021.06.016

Keywords

SARS-CoV-2 virus; Variant; B; 1; 351; CT-P59; Regdanvimab; Therapeutic antibody

Funding

  1. South African Medical Research Council Strategic Health Innovation Program
  2. South African Research Chairs Initiative of the Department of Science and Innovation
  3. NRF [9834]

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The global spread of newly emerging variants of SARS-CoV-2 poses a new threat to public health, with vaccines and antibodies showing reduced effectiveness against these variants. Research has shown that while the CT-P59 monoclonal antibody has reduced neutralizing activity against the South African variant in vitro, it is still able to decrease viral load in animals infected with the variant in vivo.
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. (c) 2021 Elsevier Inc. All rights reserved.

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