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SARS-CoV-2 neutralizing human recombinant antibodies selected from pre-pandemic healthy donors binding at RBD-ACE2

Federico Bertoglio1, Doris Meier1, Nora Langreder1

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Nature Communications
|March 12, 2021
PubMed
Summary

Researchers developed fully human antibodies against SARS-CoV-2 using phage display. One antibody, STE73-2E9, neutralizes the virus by binding the ACE2-RBD interface, offering a rapid pandemic response strategy.

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Area of Science:

  • Virology
  • Immunology
  • Biotechnology

Background:

  • COVID-19, caused by SARS-CoV-2, utilizes the human ACE2 enzyme for cell entry via the spike protein's receptor binding domain (RBD).
  • Developing effective therapeutics rapidly is crucial during pandemics.

Purpose of the Study:

  • To identify and characterize fully human antibodies targeting the SARS-CoV-2 spike protein.
  • To evaluate the neutralizing capacity of these antibodies against SARS-CoV-2 infection.

Main Methods:

  • Phage display technology was employed to screen human naïve antibody gene libraries (HAL9/10).
  • 309 unique anti-S1 antibodies were identified, with 17 targeting the RBD.
  • Selected antibodies were tested for inhibition of spike-ACE2 binding and SARS-CoV-2 neutralization in cell culture.

Main Results:

  • 17 antibodies bound the RBD and inhibited spike protein binding to ACE2-expressing cells.
  • Antibodies demonstrated neutralization of active SARS-CoV-2 infection in VeroE6 cells.
  • The antibody STE73-2E9, as IgG, neutralized SARS-CoV-2 and binds the ACE2-RBD interface.

Conclusions:

  • Phage display using universal libraries from healthy donors enables rapid generation of SARS-CoV-2 antibodies.
  • The identified antibodies, particularly STE73-2E9, show therapeutic potential for COVID-19.
  • This approach provides an advantage during pandemics by not relying on convalescent patient materials.