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Evaluation of Antibody-Dependent Fc-Mediated Viral Entry, as Compared With Neutralization, in SARS-CoV-2 Infection
Fc-mediated virus entry has been observed for many viruses, but the characterization of this activity in convalescent plasma against SARS-CoV-2 Variants of Concern (VOC) is undefined. In this study, we evaluated Fc-mediated viral entry (FVE) on FcγRIIa-expressing HEK293 cells in the presence of SARS...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9193970/ https://www.ncbi.nlm.nih.gov/pubmed/35711449 http://dx.doi.org/10.3389/fimmu.2022.901217 |
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author | Wieczorek, Lindsay Zemil, Michelle Merbah, Mélanie Dussupt, Vincent Kavusak, Erin Molnar, Sebastian Heller, Jonah Beckman, Bradley Wollen-Roberts, Suzanne Peachman, Kristina K. Darden, Janice M. Krebs, Shelly Rolland, Morgane Peel, Sheila A. Polonis, Victoria R. |
author_facet | Wieczorek, Lindsay Zemil, Michelle Merbah, Mélanie Dussupt, Vincent Kavusak, Erin Molnar, Sebastian Heller, Jonah Beckman, Bradley Wollen-Roberts, Suzanne Peachman, Kristina K. Darden, Janice M. Krebs, Shelly Rolland, Morgane Peel, Sheila A. Polonis, Victoria R. |
author_sort | Wieczorek, Lindsay |
collection | PubMed |
description | Fc-mediated virus entry has been observed for many viruses, but the characterization of this activity in convalescent plasma against SARS-CoV-2 Variants of Concern (VOC) is undefined. In this study, we evaluated Fc-mediated viral entry (FVE) on FcγRIIa-expressing HEK293 cells in the presence of SARS-CoV-2 convalescent plasma and compared it with SARS-CoV-2 pseudovirus neutralization using ACE2-expressing HEK293 cells. The plasma were collected early in the pandemic from 39 individuals. We observed both neutralization and FVE against the infecting Washington SARS-CoV-2 strain for 31% of plasmas, neutralization, but not FVE for 61% of plasmas, and no neutralization or FVE for 8% of plasmas. Neutralization titer correlated significantly with the plasma dilution at which maximum FVE was observed, indicating Fc-mediated uptake peaked as neutralization potency waned. While total Spike-specific plasma IgG levels were similar between plasma that mediated FVE and those that did not, Spike-specific plasma IgM levels were significantly higher in plasma that did not mediate FVE. Plasma neutralization titers against the Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1) and Delta (B.1.617.2) VOC were significantly lower than titers against the Washington strain, while plasma FVE activity against the VOC was either higher or similar. This is the first report to demonstrate a functional shift in convalescent plasma antibodies from neutralizing and FVE-mediating against the earlier Washington strain, to an activity mediating only FVE and no neutralization activity against the emerging VOC, specifically the Beta (B.1.351) and Gamma (P.1) VOC. It will be important to determine the in vivo relevance of these findings. |
format | Online Article Text |
id | pubmed-9193970 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-91939702022-06-15 Evaluation of Antibody-Dependent Fc-Mediated Viral Entry, as Compared With Neutralization, in SARS-CoV-2 Infection Wieczorek, Lindsay Zemil, Michelle Merbah, Mélanie Dussupt, Vincent Kavusak, Erin Molnar, Sebastian Heller, Jonah Beckman, Bradley Wollen-Roberts, Suzanne Peachman, Kristina K. Darden, Janice M. Krebs, Shelly Rolland, Morgane Peel, Sheila A. Polonis, Victoria R. Front Immunol Immunology Fc-mediated virus entry has been observed for many viruses, but the characterization of this activity in convalescent plasma against SARS-CoV-2 Variants of Concern (VOC) is undefined. In this study, we evaluated Fc-mediated viral entry (FVE) on FcγRIIa-expressing HEK293 cells in the presence of SARS-CoV-2 convalescent plasma and compared it with SARS-CoV-2 pseudovirus neutralization using ACE2-expressing HEK293 cells. The plasma were collected early in the pandemic from 39 individuals. We observed both neutralization and FVE against the infecting Washington SARS-CoV-2 strain for 31% of plasmas, neutralization, but not FVE for 61% of plasmas, and no neutralization or FVE for 8% of plasmas. Neutralization titer correlated significantly with the plasma dilution at which maximum FVE was observed, indicating Fc-mediated uptake peaked as neutralization potency waned. While total Spike-specific plasma IgG levels were similar between plasma that mediated FVE and those that did not, Spike-specific plasma IgM levels were significantly higher in plasma that did not mediate FVE. Plasma neutralization titers against the Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1) and Delta (B.1.617.2) VOC were significantly lower than titers against the Washington strain, while plasma FVE activity against the VOC was either higher or similar. This is the first report to demonstrate a functional shift in convalescent plasma antibodies from neutralizing and FVE-mediating against the earlier Washington strain, to an activity mediating only FVE and no neutralization activity against the emerging VOC, specifically the Beta (B.1.351) and Gamma (P.1) VOC. It will be important to determine the in vivo relevance of these findings. Frontiers Media S.A. 2022-05-31 /pmc/articles/PMC9193970/ /pubmed/35711449 http://dx.doi.org/10.3389/fimmu.2022.901217 Text en Copyright © 2022 Wieczorek, Zemil, Merbah, Dussupt, Kavusak, Molnar, Heller, Beckman, Wollen-Roberts, Peachman, Darden, Krebs, Rolland, Peel and Polonis https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Wieczorek, Lindsay Zemil, Michelle Merbah, Mélanie Dussupt, Vincent Kavusak, Erin Molnar, Sebastian Heller, Jonah Beckman, Bradley Wollen-Roberts, Suzanne Peachman, Kristina K. Darden, Janice M. Krebs, Shelly Rolland, Morgane Peel, Sheila A. Polonis, Victoria R. Evaluation of Antibody-Dependent Fc-Mediated Viral Entry, as Compared With Neutralization, in SARS-CoV-2 Infection |
title | Evaluation of Antibody-Dependent Fc-Mediated Viral Entry, as Compared With Neutralization, in SARS-CoV-2 Infection |
title_full | Evaluation of Antibody-Dependent Fc-Mediated Viral Entry, as Compared With Neutralization, in SARS-CoV-2 Infection |
title_fullStr | Evaluation of Antibody-Dependent Fc-Mediated Viral Entry, as Compared With Neutralization, in SARS-CoV-2 Infection |
title_full_unstemmed | Evaluation of Antibody-Dependent Fc-Mediated Viral Entry, as Compared With Neutralization, in SARS-CoV-2 Infection |
title_short | Evaluation of Antibody-Dependent Fc-Mediated Viral Entry, as Compared With Neutralization, in SARS-CoV-2 Infection |
title_sort | evaluation of antibody-dependent fc-mediated viral entry, as compared with neutralization, in sars-cov-2 infection |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9193970/ https://www.ncbi.nlm.nih.gov/pubmed/35711449 http://dx.doi.org/10.3389/fimmu.2022.901217 |
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