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Antibody screening at reduced pH enables preferential selection of potently neutralizing antibodies targeting SARS-CoV-2.

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Madan B, Reddem ER, Wang P, Casner RG, Nair MS, Huang Y, Fahad AS, de Souza MO, Banach BB, López Acevedo SN, Pan X, Nimrania R, Teng IT, Bahna F, Zhou T, Zhang B, Yin MT, Ho DD, Kwong PD, Shapiro L, DeKosky BJ
OpenAccess logo AIChE J 67 e17440 (2021)
Cited: 3 times
EuropePMC logo PMID: 34898670

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.

Articles citing this publication (3)

  1. Molecular probes of spike ectodomain and its subdomains for SARS-CoV-2 variants, Alpha through Omicron. Teng IT, Nazzari AF, Choe M, Liu T, Oliveira de Souza M, Petrova Y, Tsybovsky Y, Wang S, Zhang B, Artamonov M, Madan B, Huang A, Lopez Acevedo SN, Pan X, Ruckwardt TJ, DeKosky BJ, Mascola JR, Misasi J, Sullivan NJ, Zhou T, Kwong PD. PLoS One 17 e0268767 (2022)
  2. Large-scale antibody immune response mapping of splenic B cells and bone marrow plasma cells in a transgenic mouse model. Pan X, López Acevedo SN, Cuziol C, De Tavernier E, Fahad AS, Longjam PS, Rao SP, Aguilera-Rodríguez D, Rezé M, Bricault CA, Gutiérrez-González MF, de Souza MO, DiNapoli JM, Vigne E, Shahsavarian MA, DeKosky BJ. Front Immunol 14 1137069 (2023)
  3. Mapping monoclonal anti-SARS-CoV-2 antibody repertoires against diverse coronavirus antigens. de Souza MO, Madan B, Teng IT, Huang A, Liu L, Fahad AS, Lopez Acevedo SN, Pan X, Sastry M, Gutierrez-Gonzalez M, Yin MT, Zhou T, Ho DD, Kwong PD, DeKosky BJ. Front Immunol 13 977064 (2022)


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