Antibody Binding to SARS-CoV-2 S Glycoprotein Correlates with but Does Not Predict Neutralization
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 antibodi...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-10-01
|
| Series: | Viruses |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4915/12/11/1214 |
| _version_ | 1827703517647732736 |
|---|---|
| author | Shilei Ding Annemarie Laumaea Mehdi Benlarbi Guillaume Beaudoin-Bussières Romain Gasser Halima Medjahed Marie Pancera Leonidas Stamatatos Andrew T. McGuire Renée Bazin Andrés Finzi |
| author_facet | Shilei Ding Annemarie Laumaea Mehdi Benlarbi Guillaume Beaudoin-Bussières Romain Gasser Halima Medjahed Marie Pancera Leonidas Stamatatos Andrew T. McGuire Renée Bazin Andrés Finzi |
| author_sort | Shilei Ding |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T15:20:10Z |
| format | Article |
| id | doaj.art-d32707bb2bf54b92a0e1119285d9019e |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T15:20:10Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-d32707bb2bf54b92a0e1119285d9019e2023-11-20T18:36:57ZengMDPI AGViruses1999-49152020-10-011211121410.3390/v12111214Antibody Binding to SARS-CoV-2 S Glycoprotein Correlates with but Does Not Predict NeutralizationShilei Ding0Annemarie Laumaea1Mehdi Benlarbi2Guillaume Beaudoin-Bussières3Romain Gasser4Halima Medjahed5Marie Pancera6Leonidas Stamatatos7Andrew T. McGuire8Renée Bazin9Andrés Finzi10Centre de Recherche du CHUM, Montréal, QC H2X 0A9, CanadaCentre de Recherche du CHUM, Montréal, QC H2X 0A9, CanadaCentre de Recherche du CHUM, Montréal, QC H2X 0A9, CanadaCentre de Recherche du CHUM, Montréal, QC H2X 0A9, CanadaCentre de Recherche du CHUM, Montréal, QC H2X 0A9, CanadaCentre de Recherche du CHUM, Montréal, QC H2X 0A9, CanadaFred Hutchinson Cancer Research Center, Vaccines and Infectious Diseases Division, Seattle, 98109 WA, USAFred Hutchinson Cancer Research Center, Vaccines and Infectious Diseases Division, Seattle, 98109 WA, USAFred Hutchinson Cancer Research Center, Vaccines and Infectious Diseases Division, Seattle, 98109 WA, USAHéma-Québec, Affaires Médicales et Innovation, Québec, QC G1V 5C3, CanadaCentre de Recherche du CHUM, Montréal, QC H2X 0A9, CanadaConvalescent 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.https://www.mdpi.com/1999-4915/12/11/1214COVID-19SARS-COV-2convalescent plasmaELISAneutralizationvirus capture assay |
| spellingShingle | Shilei Ding Annemarie Laumaea Mehdi Benlarbi Guillaume Beaudoin-Bussières Romain Gasser Halima Medjahed Marie Pancera Leonidas Stamatatos Andrew T. McGuire Renée Bazin Andrés Finzi Antibody Binding to SARS-CoV-2 S Glycoprotein Correlates with but Does Not Predict Neutralization Viruses COVID-19 SARS-COV-2 convalescent plasma ELISA neutralization virus capture assay |
| title | Antibody Binding to SARS-CoV-2 S Glycoprotein Correlates with but Does Not Predict Neutralization |
| title_full | Antibody Binding to SARS-CoV-2 S Glycoprotein Correlates with but Does Not Predict Neutralization |
| title_fullStr | Antibody Binding to SARS-CoV-2 S Glycoprotein Correlates with but Does Not Predict Neutralization |
| title_full_unstemmed | Antibody Binding to SARS-CoV-2 S Glycoprotein Correlates with but Does Not Predict Neutralization |
| title_short | Antibody Binding to SARS-CoV-2 S Glycoprotein Correlates with but Does Not Predict Neutralization |
| title_sort | antibody binding to sars cov 2 s glycoprotein correlates with but does not predict neutralization |
| topic | COVID-19 SARS-COV-2 convalescent plasma ELISA neutralization virus capture assay |
| url | https://www.mdpi.com/1999-4915/12/11/1214 |
| work_keys_str_mv | AT shileiding antibodybindingtosarscov2sglycoproteincorrelateswithbutdoesnotpredictneutralization AT annemarielaumaea antibodybindingtosarscov2sglycoproteincorrelateswithbutdoesnotpredictneutralization AT mehdibenlarbi antibodybindingtosarscov2sglycoproteincorrelateswithbutdoesnotpredictneutralization AT guillaumebeaudoinbussieres antibodybindingtosarscov2sglycoproteincorrelateswithbutdoesnotpredictneutralization AT romaingasser antibodybindingtosarscov2sglycoproteincorrelateswithbutdoesnotpredictneutralization AT halimamedjahed antibodybindingtosarscov2sglycoproteincorrelateswithbutdoesnotpredictneutralization AT mariepancera antibodybindingtosarscov2sglycoproteincorrelateswithbutdoesnotpredictneutralization AT leonidasstamatatos antibodybindingtosarscov2sglycoproteincorrelateswithbutdoesnotpredictneutralization AT andrewtmcguire antibodybindingtosarscov2sglycoproteincorrelateswithbutdoesnotpredictneutralization AT reneebazin antibodybindingtosarscov2sglycoproteincorrelateswithbutdoesnotpredictneutralization AT andresfinzi antibodybindingtosarscov2sglycoproteincorrelateswithbutdoesnotpredictneutralization |