tetano
Editor, Senior Moderator
J Virol Methods
. 2021 Jan 26;290:114084.
doi: 10.1016/j.jviromet.2021.114084. Online ahead of print.
Selection, Identification, and Characterization of SARS-CoV-2 Monoclonal Antibody Resistant Mutants
Fatai S Oladunni[SUP] 1 [/SUP], Jun-Gyu Park[SUP] 2 [/SUP], Kevin Chiem[SUP] 2 [/SUP], Chengjin Ye[SUP] 2 [/SUP], Michael Pipenbrink[SUP] 3 [/SUP], Mark R Walter[SUP] 4 [/SUP], James Kobie[SUP] 3 [/SUP], Luis Martinez-Sobrido[SUP] 5 [/SUP]
Affiliations
Abstract
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, and to assess MARM viral fitness and potential to induce severe infection and associated COVID-19 disease.
Keywords: COVID-19; RBD; SARS-CoV-2; Spike glycoprotein; monoclonal antibodies; monoclonal antibody resistant mutant; neutralizing antibodies; viral drift.
. 2021 Jan 26;290:114084.
doi: 10.1016/j.jviromet.2021.114084. Online ahead of print.
Selection, Identification, and Characterization of SARS-CoV-2 Monoclonal Antibody Resistant Mutants
Fatai S Oladunni[SUP] 1 [/SUP], Jun-Gyu Park[SUP] 2 [/SUP], Kevin Chiem[SUP] 2 [/SUP], Chengjin Ye[SUP] 2 [/SUP], Michael Pipenbrink[SUP] 3 [/SUP], Mark R Walter[SUP] 4 [/SUP], James Kobie[SUP] 3 [/SUP], Luis Martinez-Sobrido[SUP] 5 [/SUP]
Affiliations
- PMID: 33513380
- PMCID: PMC7837211
- DOI: 10.1016/j.jviromet.2021.114084
Abstract
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, and to assess MARM viral fitness and potential to induce severe infection and associated COVID-19 disease.
Keywords: COVID-19; RBD; SARS-CoV-2; Spike glycoprotein; monoclonal antibodies; monoclonal antibody resistant mutant; neutralizing antibodies; viral drift.