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Antibody Binding to SARS-CoV-2 S Glycoprotein Correlates with but Does Not Predict Neutralization.
Viruses. 2020 10 26; 12(11)V

Abstract

Convalescent plasma from SARS-CoV-2 infected individuals and monoclonal antibodies were shown to potently neutralize viral and pseudoviral particles carrying the S glycoprotein. However, a non-negligent proportion of plasma samples from infected individuals, as well as S-specific monoclonal antibodies, were reported to be non-neutralizing despite efficient interaction with the S glycoprotein in different biochemical assays using soluble recombinant forms of S or when expressed at the cell surface. How neutralization relates to the binding of S glycoprotein in the context of viral particles remains to be established. Here, we developed a pseudovirus capture assay (VCA) to measure the capacity of plasma samples or antibodies immobilized on ELISA plates to bind to membrane-bound S glycoproteins from SARS-CoV-2 expressed at the surface of lentiviral particles. By performing VCA, ELISA, and neutralization assays, we observed a strong correlation between these parameters. However, while we found that plasma samples unable to capture viral particles did not neutralize, capture did not guarantee neutralization, indicating that the capacity of antibodies to bind to the S glycoprotein at the surface of pseudoviral particles is required but not sufficient to mediate neutralization. Altogether, our results highlight the importance of better understanding the inactivation of S by plasma and neutralizing antibodies.

Authors+Show Affiliations

Centre de Recherche du CHUM, Montréal, QC H2X 0A9, Canada.Centre de Recherche du CHUM, Montréal, QC H2X 0A9, Canada. Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC H2X 0A9, Canada.Centre de Recherche du CHUM, Montréal, QC H2X 0A9, Canada.Centre de Recherche du CHUM, Montréal, QC H2X 0A9, Canada. Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC H2X 0A9, Canada.Centre de Recherche du CHUM, Montréal, QC H2X 0A9, Canada. Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC H2X 0A9, Canada.Centre de Recherche du CHUM, Montréal, QC H2X 0A9, Canada.Fred Hutchinson Cancer Research Center, Vaccines and Infectious Diseases Division, Seattle, WA 98109, USA. Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institute of Health, Bethesda, MD 20892, USA.Fred Hutchinson Cancer Research Center, Vaccines and Infectious Diseases Division, Seattle, WA 98109, USA. Department of Global Health, University of Washington, Seattle, WA 98195, USA.Fred Hutchinson Cancer Research Center, Vaccines and Infectious Diseases Division, Seattle, WA 98109, USA. Department of Global Health, University of Washington, Seattle, WA 98195, USA.Héma-Québec, Affaires Médicales et Innovation, Québec, QC G1V 5C3, Canada.Centre de Recherche du CHUM, Montréal, QC H2X 0A9, Canada. Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC H2X 0A9, Canada. Department of Microbiology and Immunology, McGill University, Montreal, QC H3A 2B4, Canada.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33114742

Citation

Ding, Shilei, et al. "Antibody Binding to SARS-CoV-2 S Glycoprotein Correlates With but Does Not Predict Neutralization." Viruses, vol. 12, no. 11, 2020.
Ding S, Laumaea A, Benlarbi M, et al. Antibody Binding to SARS-CoV-2 S Glycoprotein Correlates with but Does Not Predict Neutralization. Viruses. 2020;12(11).
Ding, S., Laumaea, A., Benlarbi, M., Beaudoin-Bussières, G., Gasser, R., Medjahed, H., Pancera, M., Stamatatos, L., McGuire, A. T., Bazin, R., & Finzi, A. (2020). Antibody Binding to SARS-CoV-2 S Glycoprotein Correlates with but Does Not Predict Neutralization. Viruses, 12(11). https://doi.org/10.3390/v12111214
Ding S, et al. Antibody Binding to SARS-CoV-2 S Glycoprotein Correlates With but Does Not Predict Neutralization. Viruses. 2020 10 26;12(11) PubMed PMID: 33114742.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antibody Binding to SARS-CoV-2 S Glycoprotein Correlates with but Does Not Predict Neutralization. AU - Ding,Shilei, AU - Laumaea,Annemarie, AU - Benlarbi,Mehdi, AU - Beaudoin-Bussières,Guillaume, AU - Gasser,Romain, AU - Medjahed,Halima, AU - Pancera,Marie, AU - Stamatatos,Leonidas, AU - McGuire,Andrew T, AU - Bazin,Renée, AU - Finzi,Andrés, Y1 - 2020/10/26/ PY - 2020/10/08/received PY - 2020/10/22/accepted PY - 2020/10/29/entrez PY - 2020/10/30/pubmed PY - 2020/11/11/medline KW - COVID-19 KW - ELISA KW - SARS-COV-2 KW - convalescent plasma KW - neutralization KW - virus capture assay JF - Viruses JO - Viruses VL - 12 IS - 11 N2 - Convalescent plasma from SARS-CoV-2 infected individuals and monoclonal antibodies were shown to potently neutralize viral and pseudoviral particles carrying the S glycoprotein. However, a non-negligent proportion of plasma samples from infected individuals, as well as S-specific monoclonal antibodies, were reported to be non-neutralizing despite efficient interaction with the S glycoprotein in different biochemical assays using soluble recombinant forms of S or when expressed at the cell surface. How neutralization relates to the binding of S glycoprotein in the context of viral particles remains to be established. Here, we developed a pseudovirus capture assay (VCA) to measure the capacity of plasma samples or antibodies immobilized on ELISA plates to bind to membrane-bound S glycoproteins from SARS-CoV-2 expressed at the surface of lentiviral particles. By performing VCA, ELISA, and neutralization assays, we observed a strong correlation between these parameters. However, while we found that plasma samples unable to capture viral particles did not neutralize, capture did not guarantee neutralization, indicating that the capacity of antibodies to bind to the S glycoprotein at the surface of pseudoviral particles is required but not sufficient to mediate neutralization. Altogether, our results highlight the importance of better understanding the inactivation of S by plasma and neutralizing antibodies. SN - 1999-4915 UR - https://www.unboundmedicine.com/medline/citation/33114742/Antibody_Binding_to_SARS_CoV_2_S_Glycoprotein_Correlates_with_but_Does_Not_Predict_Neutralization_ L2 - https://www.mdpi.com/resolver?pii=v12111214 DB - PRIME DP - Unbound Medicine ER -