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Peptide Scanning-assisted Identification of a Monoclonal Antibody-recognized Linear B-cell Epitope
Published on: March 24, 2017
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Broad sarbecovirus neutralization by a human monoclonal antibody
M Alejandra Tortorici1,2, Nadine Czudnochowski3, Tyler N Starr4
1Department of Biochemistry, University of Washington, Seattle, WA, USA.
Nature
|July 19, 2021
Summary
A new human monoclonal antibody, S2X259, broadly neutralizes SARS-CoV-2 variants and other sarbecoviruses by targeting a conserved epitope. This antibody shows promise for preventing and treating infections from emergent and zoonotic coronaviruses.
Area of Science:
- Virology
- Immunology
- Drug Discovery
Background:
- Emergence of SARS-CoV-2 variants and recurrent coronavirus spillovers necessitate broadly neutralizing antibodies.
- Existing antibodies may be affected by viral antigenic drift, limiting their efficacy against future zoonotic threats.
Purpose of the Study:
- To identify and characterize a human monoclonal antibody with broad neutralizing activity against SARS-CoV-2 variants and other sarbecoviruses.
- To evaluate the therapeutic and prophylactic potential of this antibody against emergent coronavirus infections.
Main Methods:
- Characterization of a human monoclonal antibody (S2X259) targeting a conserved epitope on the SARS-CoV-2 spike protein's receptor-binding domain.
- In vitro neutralization assays, deep-mutational scanning, and in vivo studies in a hamster model.
Main Results:
- S2X259 broadly neutralizes SARS-CoV-2 variants (e.g., B.1.1.7, B.1.351) and various sarbecoviruses by inhibiting ACE2 binding.
- Limited viral escape observed, with resistance only emerging after a single amino acid substitution (G504D).
- Prophylactic and therapeutic administration of S2X259 protected hamsters against SARS-CoV-2 and B.1.351 variant challenge.
Conclusions:
- S2X259 is a promising candidate for preventing and treating infections caused by emergent SARS-CoV-2 variants and zoonotic sarbecoviruses.
- The identified conserved antigenic site targeted by S2X259 can guide the development of pan-sarbecovirus vaccines.
