Engineering SARS-CoV-2 neutralizing antibodies for increased potency and reduced viral escape pathways

Area of Science:

• Virology
• Immunology
• Biotechnology

Background:

• SARS-CoV-2 variants pose a significant threat to existing antibody and vaccine efficacy.
• Mutations in the spike (S) protein's ACE2 receptor binding site can lead to immune escape.

Purpose of the Study:

• To engineer neutralizing antibodies with enhanced binding affinity to the SARS-CoV-2 S protein.
• To assess the impact of affinity maturation on antibody neutralization potency and breadth against viral variants.

Main Methods:

• Directed evolution was employed to engineer three neutralizing antibodies.
• In vitro functional activity, including neutralization potency and breadth, was evaluated.
• Deep mutational scanning identified viral escape mutations.
• In vivo studies were conducted using the Syrian hamster model.

Main Results:

• Engineered antibodies exhibited increased in vitro functional activity against SARS-CoV-2 variants.
• Higher binding affinity correlated with a reduced number of viral escape mutations.
• Affinity-matured antibodies provided superior protection in a Syrian hamster model compared to parental antibodies.

Conclusions:

• Antibody affinity maturation is a promising strategy to enhance neutralization and combat viral escape.
• Improving antibody affinity can reduce viral escape pathways, offering better protection against evolving SARS-CoV-2 variants.
• Affinity maturation of vaccine components may improve resistance to viral variation.