Selection, identification, and characterization of SARS-CoV-2 monoclonal antibody resistant mutants.


Journal

Journal of virological methods
ISSN: 1879-0984
Titre abrégé: J Virol Methods
Pays: Netherlands
ID NLM: 8005839

Informations de publication

Date de publication:
04 2021
Historique:
received: 28 10 2020
revised: 10 01 2021
accepted: 23 01 2021
pubmed: 30 1 2021
medline: 26 3 2021
entrez: 29 1 2021
Statut: ppublish

Résumé

The use of monoclonal neutralizing antibodies (mNAbs) is being actively pursued as a viable intervention for the treatment of Severe Acute Respiratory Syndrome CoV-2 (SARS-CoV-2) infection and associated coronavirus disease 2019 (COVID-19). While highly potent mNAbs have great therapeutic potential, the ability of the virus to mutate and escape recognition and neutralization of mNAbs represents a potential problem in their use for the therapeutic management of SARS-CoV-2. Studies investigating natural or mNAb-induced antigenic variability in the receptor binding domain (RBD) of SARS-CoV-2 Spike (S) glycoprotein, and their effects on viral fitness are still rudimentary. In this manuscript we described experimental approaches for the selection, identification, and characterization of SARS-CoV-2 monoclonal antibody resistant mutants (MARMs) in cultured cells. The ability to study SARS-CoV-2 antigenic drift under selective immune pressure by mNAbs is important for the optimal implementation of mNAbs for the therapeutic management of COVID-19. This will help to identify essential amino acid residues in the viral S glycoprotein required for mNAb-mediated inhibition of viral infection, to predict potential natural drift variants that could emerge upon implementation of therapeutic mNAbs, as well as vaccine prophylactic treatments for SARS-CoV-2 infection. Additionally, it will also enable the assessment of MARM viral fitness and its potential to induce severe infection and associated COVID-19 disease.

Identifiants

pubmed: 33513380
pii: S0166-0934(21)00023-9
doi: 10.1016/j.jviromet.2021.114084
pmc: PMC7837211
pii:
doi:

Substances chimiques

Antibodies, Monoclonal 0
Antibodies, Neutralizing 0
Spike Glycoprotein, Coronavirus 0
spike protein, SARS-CoV-2 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

114084

Subventions

Organisme : NIAID NIH HHS
ID : R01 AI145332
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI161175
Pays : United States

Informations de copyright

Copyright © 2021 Elsevier B.V. All rights reserved.

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Auteurs

Fatai S Oladunni (FS)

Texas Biomedical Research Institute, San Antonio, TX, USA; Department of Veterinary Microbiology, University of Ilorin, Nigeria.

Jun-Gyu Park (JG)

Texas Biomedical Research Institute, San Antonio, TX, USA.

Kevin Chiem (K)

Texas Biomedical Research Institute, San Antonio, TX, USA.

Chengjin Ye (C)

Texas Biomedical Research Institute, San Antonio, TX, USA.

Michael Pipenbrink (M)

Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, AL, USA.

Mark R Walter (MR)

Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA.

James Kobie (J)

Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, AL, USA.

Luis Martinez-Sobrido (L)

Texas Biomedical Research Institute, San Antonio, TX, USA. Electronic address: lmartinez@txbiomed.org.

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Classifications MeSH