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Simultaneous measurement of multiple variant-specific SARS-CoV-2 neutralizing antibodies with a multiplexed flow cytometric assay
INTRODUCTION: Neutralizing antibodies (NAbs) have been recognized as surrogates of protection against SARS-CoV-2; however, the emergence of variants/subvariants escaping neutralization suggests that laboratory assessments of NAbs against the ancestral/wild type (WT) antigens likely overestimate the...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9732243/ https://www.ncbi.nlm.nih.gov/pubmed/36505453 http://dx.doi.org/10.3389/fimmu.2022.1039163 |
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author | Liu, Hong Varvel, Stephen Chen, Ge McConnell, Joseph Caffrey, Rebecca Galdzicka, Marzena Shabahang, Shahrokh |
author_facet | Liu, Hong Varvel, Stephen Chen, Ge McConnell, Joseph Caffrey, Rebecca Galdzicka, Marzena Shabahang, Shahrokh |
author_sort | Liu, Hong |
collection | PubMed |
description | INTRODUCTION: Neutralizing antibodies (NAbs) have been recognized as surrogates of protection against SARS-CoV-2; however, the emergence of variants/subvariants escaping neutralization suggests that laboratory assessments of NAbs against the ancestral/wild type (WT) antigens likely overestimate the degree of protection. METHODS: A novel flow cytometry-based multiplex test system was developed for the simultaneous detection of NAbs of multiple SARS-CoV-2 variants. SARS-CoV-2 antibodies (Abs) including IgG, IgM, IgA isotypes were measured in the same system. Samples from negative, convalesced, vaccinated, boosted, and breakthrough infection (BTI) populations were tested for both NAbs and Abs. RESULTS: NAbs induced by WT showed neutralization activity that correlated strongly to all variants (R(2) > 0.85) except omicron BA.1/BA.2 (R(2) <0.50). Two doses of vaccine elicited very little protective immunity against BA.1/BA.2, though a booster dose significantly improved NAbs for all variants. NAbs/Abs increased more following BTI than after a booster, suggesting that hybrid immunity (vaccination + natural immunity) was more robust to all variants including BA.1/BA.2. BTIs occurring in the omicron era led to stronger NAb responses against BA.1/BA.2 than did older BTIs. In all comparisons, the RBD antigens demonstrated greater differences between WT and BA.1/BA.2 than the spike antigens. DISCUSSION: Taken together, we demonstrated that both Ab and NAb against multiple SARS-CoV-2 variants/subvariants can be reliably detected on the same multiplex platform. Distinguishing NAbs to the appropriate antigenic target of prevalent variants offers the best correlate of protection and aids individual decisions about the appropriateness and cadence of vaccine boosters and other exposure mitigation strategies. |
format | Online Article Text |
id | pubmed-9732243 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-97322432022-12-10 Simultaneous measurement of multiple variant-specific SARS-CoV-2 neutralizing antibodies with a multiplexed flow cytometric assay Liu, Hong Varvel, Stephen Chen, Ge McConnell, Joseph Caffrey, Rebecca Galdzicka, Marzena Shabahang, Shahrokh Front Immunol Immunology INTRODUCTION: Neutralizing antibodies (NAbs) have been recognized as surrogates of protection against SARS-CoV-2; however, the emergence of variants/subvariants escaping neutralization suggests that laboratory assessments of NAbs against the ancestral/wild type (WT) antigens likely overestimate the degree of protection. METHODS: A novel flow cytometry-based multiplex test system was developed for the simultaneous detection of NAbs of multiple SARS-CoV-2 variants. SARS-CoV-2 antibodies (Abs) including IgG, IgM, IgA isotypes were measured in the same system. Samples from negative, convalesced, vaccinated, boosted, and breakthrough infection (BTI) populations were tested for both NAbs and Abs. RESULTS: NAbs induced by WT showed neutralization activity that correlated strongly to all variants (R(2) > 0.85) except omicron BA.1/BA.2 (R(2) <0.50). Two doses of vaccine elicited very little protective immunity against BA.1/BA.2, though a booster dose significantly improved NAbs for all variants. NAbs/Abs increased more following BTI than after a booster, suggesting that hybrid immunity (vaccination + natural immunity) was more robust to all variants including BA.1/BA.2. BTIs occurring in the omicron era led to stronger NAb responses against BA.1/BA.2 than did older BTIs. In all comparisons, the RBD antigens demonstrated greater differences between WT and BA.1/BA.2 than the spike antigens. DISCUSSION: Taken together, we demonstrated that both Ab and NAb against multiple SARS-CoV-2 variants/subvariants can be reliably detected on the same multiplex platform. Distinguishing NAbs to the appropriate antigenic target of prevalent variants offers the best correlate of protection and aids individual decisions about the appropriateness and cadence of vaccine boosters and other exposure mitigation strategies. Frontiers Media S.A. 2022-11-25 /pmc/articles/PMC9732243/ /pubmed/36505453 http://dx.doi.org/10.3389/fimmu.2022.1039163 Text en Copyright © 2022 Liu, Varvel, Chen, McConnell, Caffrey, Galdzicka and Shabahang 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 Liu, Hong Varvel, Stephen Chen, Ge McConnell, Joseph Caffrey, Rebecca Galdzicka, Marzena Shabahang, Shahrokh Simultaneous measurement of multiple variant-specific SARS-CoV-2 neutralizing antibodies with a multiplexed flow cytometric assay |
title | Simultaneous measurement of multiple variant-specific SARS-CoV-2 neutralizing antibodies with a multiplexed flow cytometric assay |
title_full | Simultaneous measurement of multiple variant-specific SARS-CoV-2 neutralizing antibodies with a multiplexed flow cytometric assay |
title_fullStr | Simultaneous measurement of multiple variant-specific SARS-CoV-2 neutralizing antibodies with a multiplexed flow cytometric assay |
title_full_unstemmed | Simultaneous measurement of multiple variant-specific SARS-CoV-2 neutralizing antibodies with a multiplexed flow cytometric assay |
title_short | Simultaneous measurement of multiple variant-specific SARS-CoV-2 neutralizing antibodies with a multiplexed flow cytometric assay |
title_sort | simultaneous measurement of multiple variant-specific sars-cov-2 neutralizing antibodies with a multiplexed flow cytometric assay |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9732243/ https://www.ncbi.nlm.nih.gov/pubmed/36505453 http://dx.doi.org/10.3389/fimmu.2022.1039163 |
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