Affiliations
- Suzhou Medical College, Soochow University, Suzhou 215123, China.
- Key Laboratory of Immune Response and Immunotherapy, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Shanghai 200031, China.
- CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China.
- The CAS Key Laboratory of Receptor Research and State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201210, China.
- Shanghai Sci-Tech Inno Center for Infection & Immunity, Shanghai 200052, China.
PMID: 38675908 PMCID: PMC11053997 DOI: 10.3390/v16040566
Abstract
Background: Neutralizing antibodies (nAbs) play an essential role in combating SARS-CoV-2 infections. Previous studies have shown that Ab08, a potent RBD-binding nAb, effectively neutralized the prototype SARS-CoV-2 and several variants but exhibited reduced efficacy against the L452R mutation.
Methods: To overcome this limitation, several structure-based derivatives of Ab08 were developed. Among them, Ab08-K99E showed the most enhanced neutralizing potency against the Delta variant with the L452R mutation.
Results: Ab08-K99E also exhibited high binding properties and affinities to the RBDs of the prototype, Delta, and Omicron BA.4/5 variants. This derivative demonstrated improved neutralization against multiple SARS-CoV-2 variants compared to the original Ab08.
Conclusion: The optimized nAb Ab08-K99E is a promising candidate for combating SARS-CoV-2 variants, highlighting structure-based optimization as an effective approach for antibody development against evolving pathogens.
Keywords: COVID-19; L452R mutation; neutralizing antibody; structure-based antibody optimization.
