ジャーナル: AIChE J / 年: 2021 タイトル: Antibody screening at reduced pH enables preferential selection of potently neutralizing antibodies targeting SARS-CoV-2. 著者: Bharat Madan / Eswar R Reddem / Pengfei Wang / Ryan G Casner / Manoj S Nair / Yaoxing Huang / Ahmed S Fahad / Matheus Oliveira de Souza / Bailey B Banach / Sheila N López Acevedo / Xiaoli ...著者: Bharat Madan / Eswar R Reddem / Pengfei Wang / Ryan G Casner / Manoj S Nair / Yaoxing Huang / Ahmed S Fahad / Matheus Oliveira de Souza / Bailey B Banach / Sheila N López Acevedo / Xiaoli Pan / Rajani Nimrania / I-Ting Teng / Fabiana Bahna / Tongqing Zhou / Baoshan Zhang / Michael T Yin / David D Ho / Peter D Kwong / Lawrence Shapiro / Brandon J DeKosky / 要旨: 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 ...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.