Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike

Area of Science:

• Virology
• Immunology
• Structural Biology

Background:

• The ongoing severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic necessitates the development of effective treatments and preventative measures.
• Monoclonal antibodies targeting SARS-CoV-2 are a promising therapeutic strategy to combat the virus.

Purpose of the Study:

• To isolate and characterize SARS-CoV-2-neutralizing monoclonal antibodies from patients with severe coronavirus disease 2019 (COVID-19).
• To evaluate the potency and epitope targets of these antibodies for potential clinical development.

Main Methods:

• Isolation of monoclonal antibodies from five hospitalized COVID-19 patients.
• In vitro neutralization assays to determine virus-inhibitory concentrations.
• Epitope mapping and cryo-electron microscopy to identify antibody binding sites and spike protein conformations.

Main Results:

• Sixty-one SARS-CoV-2-neutralizing monoclonal antibodies were isolated.
• Nineteen antibodies demonstrated potent in vitro neutralization, with nine showing very high potency (0.7-9 ng/ml).
• Antibodies targeted the receptor-binding domain (RBD) and N-terminal domain (NTD), recognizing the closed spike conformation.

Conclusions:

• A collection of potent SARS-CoV-2-neutralizing monoclonal antibodies has been identified.
• These antibodies, targeting key regions of the viral spike protein, show promise as therapeutic and prophylactic agents against SARS-CoV-2.
• Structural analysis provides insights into antibody-spike interactions, guiding further development.