A flow cytometry-based neutralization assay for simultaneous evaluation of blocking antibodies against SARS-CoV-2 variants
Vaccines against SARS-CoV-2 have alleviated infection rates, hospitalization and deaths associated with COVID-19. In order to monitor humoral immunity, several serology tests have been developed, but the recent emergence of variants of concern has revealed the need for assays that predict the neutra...
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Language: | English |
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Frontiers Media S.A.
2022-11-01
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Series: | Frontiers in Immunology |
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Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1014309/full |
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author | Leire Egia-Mendikute Alexandre Bosch Endika Prieto-Fernández Laura Vila-Vecilla Samanta Romina Zanetti So Young Lee Borja Jiménez-Lasheras Ana García del Río Asier Antoñana-Vildosola Ander de Blas Paloma Velasco-Beltrán Marina Serrano-Maciá Paula Iruzubieta Majid Mehrpouyan Edward M. Goldberg Scott J. Bornheimer Nieves Embade María L. Martínez-Chantar María L. Martínez-Chantar Marcos López-Hoyos José M. Mato José M. Mato Óscar Millet Óscar Millet Asís Palazón Asís Palazón |
author_facet | Leire Egia-Mendikute Alexandre Bosch Endika Prieto-Fernández Laura Vila-Vecilla Samanta Romina Zanetti So Young Lee Borja Jiménez-Lasheras Ana García del Río Asier Antoñana-Vildosola Ander de Blas Paloma Velasco-Beltrán Marina Serrano-Maciá Paula Iruzubieta Majid Mehrpouyan Edward M. Goldberg Scott J. Bornheimer Nieves Embade María L. Martínez-Chantar María L. Martínez-Chantar Marcos López-Hoyos José M. Mato José M. Mato Óscar Millet Óscar Millet Asís Palazón Asís Palazón |
author_sort | Leire Egia-Mendikute |
collection | DOAJ |
description | Vaccines against SARS-CoV-2 have alleviated infection rates, hospitalization and deaths associated with COVID-19. In order to monitor humoral immunity, several serology tests have been developed, but the recent emergence of variants of concern has revealed the need for assays that predict the neutralizing capacity of antibodies in a fast and adaptable manner. Sensitive and fast neutralization assays would allow a timely evaluation of immunity against emerging variants and support drug and vaccine discovery efforts. Here we describe a simple, fast, and cell-free multiplexed flow cytometry assay to interrogate the ability of antibodies to prevent the interaction of Angiotensin-converting enzyme 2 (ACE2) and the receptor binding domain (RBD) of the original Wuhan-1 SARS-CoV-2 strain and emerging variants simultaneously, as a surrogate neutralization assay. Using this method, we demonstrate that serum antibodies collected from representative individuals at different time-points during the pandemic present variable neutralizing activity against emerging variants, such as Omicron BA.1 and South African B.1.351. Importantly, antibodies present in samples collected during 2021, before the third dose of the vaccine was administered, do not confer complete neutralization against Omicron BA.1, as opposed to samples collected in 2022 which show significant neutralizing activity. The proposed approach has a comparable performance to other established surrogate methods such as cell-based assays using pseudotyped lentiviral particles expressing the spike of SARS-CoV-2, as demonstrated by the assessment of the blocking activity of therapeutic antibodies (i.e. Imdevimab) and serum samples. This method offers a scalable, cost effective and adaptable platform for the dynamic evaluation of antibody protection in affected populations against variants of SARS-CoV-2. |
first_indexed | 2024-04-12T04:48:36Z |
format | Article |
id | doaj.art-f1a79275891c4ccc8b0bee29864100b3 |
institution | Directory Open Access Journal |
issn | 1664-3224 |
language | English |
last_indexed | 2024-04-12T04:48:36Z |
publishDate | 2022-11-01 |
publisher | Frontiers Media S.A. |
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series | Frontiers in Immunology |
spelling | doaj.art-f1a79275891c4ccc8b0bee29864100b32022-12-22T03:47:25ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-11-011310.3389/fimmu.2022.10143091014309A flow cytometry-based neutralization assay for simultaneous evaluation of blocking antibodies against SARS-CoV-2 variantsLeire Egia-Mendikute0Alexandre Bosch1Endika Prieto-Fernández2Laura Vila-Vecilla3Samanta Romina Zanetti4So Young Lee5Borja Jiménez-Lasheras6Ana García del Río7Asier Antoñana-Vildosola8Ander de Blas9Paloma Velasco-Beltrán10Marina Serrano-Maciá11Paula Iruzubieta12Majid Mehrpouyan13Edward M. Goldberg14Scott J. Bornheimer15Nieves Embade16María L. Martínez-Chantar17María L. Martínez-Chantar18Marcos López-Hoyos19José M. Mato20José M. Mato21Óscar Millet22Óscar Millet23Asís Palazón24Asís Palazón25Cancer Immunology and Immunotherapy Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Derio, SpainCancer Immunology and Immunotherapy Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Derio, SpainCancer Immunology and Immunotherapy Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Derio, SpainCancer Immunology and Immunotherapy Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Derio, SpainCancer Immunology and Immunotherapy Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Derio, SpainCancer Immunology and Immunotherapy Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Derio, SpainCancer Immunology and Immunotherapy Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Derio, SpainCancer Immunology and Immunotherapy Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Derio, SpainCancer Immunology and Immunotherapy Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Derio, SpainCancer Immunology and Immunotherapy Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Derio, SpainCancer Immunology and Immunotherapy Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Derio, SpainLiver Disease Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Derio, SpainServicio Inmunología, Hospital Universitario Marqués de Valdecilla-IDIVAL, Cantabria, SpainBD Biosciences, San Jose, CA, United StatesBD Biosciences, San Jose, CA, United StatesBD Biosciences, San Jose, CA, United StatesPrecision Medicine and Metabolism Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Derio, SpainLiver Disease Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Derio, SpainCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, SpainServicio Inmunología, Hospital Universitario Marqués de Valdecilla-IDIVAL, Cantabria, SpainPrecision Medicine and Metabolism Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Derio, SpainCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, SpainPrecision Medicine and Metabolism Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Derio, SpainCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, SpainCancer Immunology and Immunotherapy Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Derio, SpainIkerbasque, Basque Foundation for Science, Bizkaia, SpainVaccines against SARS-CoV-2 have alleviated infection rates, hospitalization and deaths associated with COVID-19. In order to monitor humoral immunity, several serology tests have been developed, but the recent emergence of variants of concern has revealed the need for assays that predict the neutralizing capacity of antibodies in a fast and adaptable manner. Sensitive and fast neutralization assays would allow a timely evaluation of immunity against emerging variants and support drug and vaccine discovery efforts. Here we describe a simple, fast, and cell-free multiplexed flow cytometry assay to interrogate the ability of antibodies to prevent the interaction of Angiotensin-converting enzyme 2 (ACE2) and the receptor binding domain (RBD) of the original Wuhan-1 SARS-CoV-2 strain and emerging variants simultaneously, as a surrogate neutralization assay. Using this method, we demonstrate that serum antibodies collected from representative individuals at different time-points during the pandemic present variable neutralizing activity against emerging variants, such as Omicron BA.1 and South African B.1.351. Importantly, antibodies present in samples collected during 2021, before the third dose of the vaccine was administered, do not confer complete neutralization against Omicron BA.1, as opposed to samples collected in 2022 which show significant neutralizing activity. The proposed approach has a comparable performance to other established surrogate methods such as cell-based assays using pseudotyped lentiviral particles expressing the spike of SARS-CoV-2, as demonstrated by the assessment of the blocking activity of therapeutic antibodies (i.e. Imdevimab) and serum samples. This method offers a scalable, cost effective and adaptable platform for the dynamic evaluation of antibody protection in affected populations against variants of SARS-CoV-2.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1014309/fullSARS-CoV-2COVID-19antibodiesflow cytometryneutralizationbeads array |
spellingShingle | Leire Egia-Mendikute Alexandre Bosch Endika Prieto-Fernández Laura Vila-Vecilla Samanta Romina Zanetti So Young Lee Borja Jiménez-Lasheras Ana García del Río Asier Antoñana-Vildosola Ander de Blas Paloma Velasco-Beltrán Marina Serrano-Maciá Paula Iruzubieta Majid Mehrpouyan Edward M. Goldberg Scott J. Bornheimer Nieves Embade María L. Martínez-Chantar María L. Martínez-Chantar Marcos López-Hoyos José M. Mato José M. Mato Óscar Millet Óscar Millet Asís Palazón Asís Palazón A flow cytometry-based neutralization assay for simultaneous evaluation of blocking antibodies against SARS-CoV-2 variants Frontiers in Immunology SARS-CoV-2 COVID-19 antibodies flow cytometry neutralization beads array |
title | A flow cytometry-based neutralization assay for simultaneous evaluation of blocking antibodies against SARS-CoV-2 variants |
title_full | A flow cytometry-based neutralization assay for simultaneous evaluation of blocking antibodies against SARS-CoV-2 variants |
title_fullStr | A flow cytometry-based neutralization assay for simultaneous evaluation of blocking antibodies against SARS-CoV-2 variants |
title_full_unstemmed | A flow cytometry-based neutralization assay for simultaneous evaluation of blocking antibodies against SARS-CoV-2 variants |
title_short | A flow cytometry-based neutralization assay for simultaneous evaluation of blocking antibodies against SARS-CoV-2 variants |
title_sort | flow cytometry based neutralization assay for simultaneous evaluation of blocking antibodies against sars cov 2 variants |
topic | SARS-CoV-2 COVID-19 antibodies flow cytometry neutralization beads array |
url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1014309/full |
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