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Adapting Neutralizing Antibodies to Viral Variants by Structure-Guided Affinity Maturation Using Phage Display
Frederik Peissert1, Mattia Pedotti2, Riccardo Corbellari1
1Philochem AG Libernstrasse 3 Otelfingen 8112 Switzerland.
Global Challenges (Hoboken, NJ)
|October 13, 2023
Summary
Researchers developed a method to rapidly adapt existing neutralizing antibodies against new pathogen variants. This structure-guided affinity maturation approach enhances antibody efficacy against evolving viruses like SARS-CoV-2 without compromising activity against earlier strains.
Area of Science:
- Immunology
- Virology
- Biotechnology
Background:
- Neutralizing monoclonal antibodies are effective therapeutics for infectious diseases.
- Antibody efficacy diminishes with target antigen mutations in emerging pathogen variants.
- Developing new antibodies for each variant is time-consuming and costly.
Purpose of the Study:
- To present a methodology for rapidly evolving existing neutralizing antibodies.
- To improve antibody function against new pathogen variants while retaining activity against previous ones.
- To demonstrate the application of this method for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants.
Main Methods:
- Structure-guided affinity maturation using combinatorial mutagenesis.
- Phage display technology for antibody selection.
- Application to a bispecific antibody (CoV-X2) against SARS-CoV-2 variants, including Delta.
Main Results:
- The evolved antibodies showed significantly improved neutralization potency against the Delta variant.
- No loss of efficacy was observed against previously targeted viral sequences.
- The method successfully adapted a neutralizing antibody to a new viral variant.
Conclusions:
- Structure-guided affinity maturation is a viable strategy for rapid antibody adaptation.
- This approach can accelerate the development of therapeutics against evolving infectious diseases.
- The methodology is broadly applicable to various pathogens and their variants.
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