AI Article Synopsis
- Antiviral monoclonal antibody (mAb) discovery aims to develop effective treatments for viral infections, but traditional methods are often inefficient due to the high affinity of antibodies not always translating to neutralizing activity.
- Researchers explored screening for anti-SARS-CoV-2 mAbs at lower pH levels, specifically pH 4.5, and found that neutralizing antibodies were more effectively enriched at this acidity compared to physiological pH (7.4).
- A new antibody, LP5, was identified that targets a key area of the SARS-CoV-2 virus, demonstrating the potential of low pH screening to enhance the discovery of effective antiviral antibodies.
Article Abstract
Antiviral monoclonal antibody (mAb) discovery enables the development of antibody-based antiviral therapeutics. Traditional antiviral mAb discovery relies on affinity between antibody and a viral antigen to discover potent neutralizing antibodies, but these approaches are inefficient because many high affinity mAbs have no neutralizing activity. We sought to determine whether screening for anti-SARS-CoV-2 mAbs at reduced pH could provide more efficient neutralizing antibody discovery. We mined the antibody response of a convalescent COVID-19 patient at both physiological pH (7.4) and reduced pH (4.5), revealing that SARS-CoV-2 neutralizing antibodies were preferentially enriched in pH 4.5 yeast display sorts. Structural analysis revealed that a potent new antibody called LP5 targets the SARS-CoV-2 N-terminal domain supersite via a unique binding recognition mode. Our data combine with evidence from prior studies to support antibody screening at pH 4.5 to accelerate antiviral neutralizing antibody discovery.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8646896 | PMC |
| http://dx.doi.org/10.1002/aic.17440 | DOI Listing |
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