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TitleAntibody screening at reduced pH enables preferential selection of potently neutralizing antibodies targeting SARS-CoV-2.
Journal, issue, pagesAIChE J, Vol. 67, Issue 12, Page e17440, Year 2021
Publish dateOct 4, 2021
AuthorsBharat 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 /
PubMed AbstractAntiviral 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.
External linksAIChE J / PubMed:34898670 / PubMed Central
MethodsEM (single particle)
Resolution4.46 Å
Structure data

24075

7mxp

EMDB-24075, PDB-7mxp:
Cryo-EM structure of NTD-directed neutralizing antibody LP5 Fab in complex with SARS-CoV-2 S2P spike
Method: EM (single particle) / Resolution: 4.46 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • severe acute respiratory syndrome coronavirus 2
  • homo sapiens (human)
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / Neturalsing antibody / Fusion protein / Spike glycoprotein / NRD / NTD-directed antibody / LP5 / Viral Protein / IMMUNE SYSTEM / Viral Protein-IMMUNE SYSTEM complex

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