Development of neutralizing antibodies against SARS-CoV-2, using a high-throughput single-B-cell cloning method

Area of Science:

• Immunology
• Virology
• Structural Biology

Background:

• Developing effective neutralizing antibodies (nAbs) from virus-infected patients is crucial.
• Current strategies for isolating nAbs require rapid and efficient methods.

Purpose of the Study:

• To report a high-throughput single-B-cell cloning method for isolating nAbs targeting diverse SARS-CoV-2 receptor binding domain (RBD) epitopes.
• To demonstrate the method's simplicity, speed, and efficiency in generating SARS-CoV-2-neutralizing antibodies.

Main Methods:

• High-throughput single-B-cell cloning for isolating nAbs from convalescent COVID-19 patients' B cells.
• Utilized cryo-electron microscopy (CryoEM) and crystallography to determine antibody-RBD binding structures.
• Live virus assays were performed to assess nAb efficacy in blocking viral entry.

Main Results:

• Successfully developed multiple nAbs targeting distinct SARS-CoV-2-RBD epitopes.
• Structural analysis revealed precise binding mechanisms of the identified nAbs to RBD.
• Demonstrated that the developed nAbs effectively block viral entry into host cells in live virus assays.

Conclusions:

• The developed method is simple, fast, and highly efficient for isolating SARS-CoV-2-neutralizing antibodies.
• This approach holds potential for developing human therapeutic antibodies for various diseases.
• The method could be valuable for future pandemic preparedness.