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Severe Acute Respiratory Syndrome Coronavirus 2 Receptor (Human Angiotensin-Converting Enzyme 2) Binding Inhibition Assay: A Rapid, High-Throughput Assay Useful for Vaccine Immunogenicity Evaluation

Emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) show immune evasion of vaccine-derived immunity, highlighting the need for better clinical immunogenicity biomarkers. To address this need, an enzyme-linked immunosorbent assay-based, human angiotensin-converting enzym...

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Autores principales: Plested, Joyce S., Zhu, Mingzhu, Cloney-Clark, Shane, Massuda, Edmond, Patel, Urvashi, Klindworth, Andrew, Massare, Michael J., Cai, Rongman, Fries, Louis, Glenn, Greg, Kalkeri, Raj
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9965183/
https://www.ncbi.nlm.nih.gov/pubmed/36838333
http://dx.doi.org/10.3390/microorganisms11020368
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author Plested, Joyce S.
Zhu, Mingzhu
Cloney-Clark, Shane
Massuda, Edmond
Patel, Urvashi
Klindworth, Andrew
Massare, Michael J.
Cai, Rongman
Fries, Louis
Glenn, Greg
Kalkeri, Raj
author_facet Plested, Joyce S.
Zhu, Mingzhu
Cloney-Clark, Shane
Massuda, Edmond
Patel, Urvashi
Klindworth, Andrew
Massare, Michael J.
Cai, Rongman
Fries, Louis
Glenn, Greg
Kalkeri, Raj
author_sort Plested, Joyce S.
collection PubMed
description Emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) show immune evasion of vaccine-derived immunity, highlighting the need for better clinical immunogenicity biomarkers. To address this need, an enzyme-linked immunosorbent assay-based, human angiotensin-converting enzyme 2 (hACE2) binding inhibition assay was developed to measure antibodies against the ancestral strain of SARS-CoV-2 and was validated for precision, specificity, linearity, and other parameters. This assay measures the inhibition of SARS-CoV-2 spike (S) protein binding to the receptor, hACE2, by serum from vaccine clinical trials. Inter- and intra-assay precision, specificity, linearity, lower limit of quantitation, and assay robustness parameters successfully met the acceptance criteria. Heme and lipid matrix effects showed minimal interference on the assay. Samples were stable for testing in the assay even with 8 freeze/thaws and up to 24 months in −80 °C storage. The assay was also adapted for variants (Delta and Omicron BA.1/BA.5), with similar validation results. The hACE2 assay showed significant correlation with anti-recombinant S immunoglobulin G levels and neutralizing antibody titers. This assay provides a rapid, high-throughput option to evaluate vaccine immunogenicity. Along with other clinical biomarkers, it can provide valuable insights into immune evasion and correlates of protection and enable vaccine development against emerging COVID-19 variants.
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spelling pubmed-99651832023-02-26 Severe Acute Respiratory Syndrome Coronavirus 2 Receptor (Human Angiotensin-Converting Enzyme 2) Binding Inhibition Assay: A Rapid, High-Throughput Assay Useful for Vaccine Immunogenicity Evaluation Plested, Joyce S. Zhu, Mingzhu Cloney-Clark, Shane Massuda, Edmond Patel, Urvashi Klindworth, Andrew Massare, Michael J. Cai, Rongman Fries, Louis Glenn, Greg Kalkeri, Raj Microorganisms Article Emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) show immune evasion of vaccine-derived immunity, highlighting the need for better clinical immunogenicity biomarkers. To address this need, an enzyme-linked immunosorbent assay-based, human angiotensin-converting enzyme 2 (hACE2) binding inhibition assay was developed to measure antibodies against the ancestral strain of SARS-CoV-2 and was validated for precision, specificity, linearity, and other parameters. This assay measures the inhibition of SARS-CoV-2 spike (S) protein binding to the receptor, hACE2, by serum from vaccine clinical trials. Inter- and intra-assay precision, specificity, linearity, lower limit of quantitation, and assay robustness parameters successfully met the acceptance criteria. Heme and lipid matrix effects showed minimal interference on the assay. Samples were stable for testing in the assay even with 8 freeze/thaws and up to 24 months in −80 °C storage. The assay was also adapted for variants (Delta and Omicron BA.1/BA.5), with similar validation results. The hACE2 assay showed significant correlation with anti-recombinant S immunoglobulin G levels and neutralizing antibody titers. This assay provides a rapid, high-throughput option to evaluate vaccine immunogenicity. Along with other clinical biomarkers, it can provide valuable insights into immune evasion and correlates of protection and enable vaccine development against emerging COVID-19 variants. MDPI 2023-02-01 /pmc/articles/PMC9965183/ /pubmed/36838333 http://dx.doi.org/10.3390/microorganisms11020368 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Plested, Joyce S.
Zhu, Mingzhu
Cloney-Clark, Shane
Massuda, Edmond
Patel, Urvashi
Klindworth, Andrew
Massare, Michael J.
Cai, Rongman
Fries, Louis
Glenn, Greg
Kalkeri, Raj
Severe Acute Respiratory Syndrome Coronavirus 2 Receptor (Human Angiotensin-Converting Enzyme 2) Binding Inhibition Assay: A Rapid, High-Throughput Assay Useful for Vaccine Immunogenicity Evaluation
title Severe Acute Respiratory Syndrome Coronavirus 2 Receptor (Human Angiotensin-Converting Enzyme 2) Binding Inhibition Assay: A Rapid, High-Throughput Assay Useful for Vaccine Immunogenicity Evaluation
title_full Severe Acute Respiratory Syndrome Coronavirus 2 Receptor (Human Angiotensin-Converting Enzyme 2) Binding Inhibition Assay: A Rapid, High-Throughput Assay Useful for Vaccine Immunogenicity Evaluation
title_fullStr Severe Acute Respiratory Syndrome Coronavirus 2 Receptor (Human Angiotensin-Converting Enzyme 2) Binding Inhibition Assay: A Rapid, High-Throughput Assay Useful for Vaccine Immunogenicity Evaluation
title_full_unstemmed Severe Acute Respiratory Syndrome Coronavirus 2 Receptor (Human Angiotensin-Converting Enzyme 2) Binding Inhibition Assay: A Rapid, High-Throughput Assay Useful for Vaccine Immunogenicity Evaluation
title_short Severe Acute Respiratory Syndrome Coronavirus 2 Receptor (Human Angiotensin-Converting Enzyme 2) Binding Inhibition Assay: A Rapid, High-Throughput Assay Useful for Vaccine Immunogenicity Evaluation
title_sort severe acute respiratory syndrome coronavirus 2 receptor (human angiotensin-converting enzyme 2) binding inhibition assay: a rapid, high-throughput assay useful for vaccine immunogenicity evaluation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9965183/
https://www.ncbi.nlm.nih.gov/pubmed/36838333
http://dx.doi.org/10.3390/microorganisms11020368
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