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A point-of-care lateral flow assay for neutralising antibodies against SARS-CoV-2
BACKGROUND: As vaccines against SARS-CoV-2 are now being rolled out, a better understanding of immunity to the virus, whether from infection, or passive or active immunisation, and the durability of this protection is required. This will benefit from the ability to measure antibody-based protection...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8641961/ https://www.ncbi.nlm.nih.gov/pubmed/34871960 http://dx.doi.org/10.1016/j.ebiom.2021.103729 |
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author | Fulford, Thomas S. Van, Huy Gherardin, Nicholas A. Zheng, Shuning Ciula, Marcin Drummer, Heidi E. Redmond, Samuel Tan, Hyon-Xhi Boo, Irene Center, Rob J. Li, Fan Grimley, Samantha L. Wines, Bruce D. Nguyen, Thi H.O. Mordant, Francesca L. Ellenberg, Paula Rowntree, Louise C. Kedzierski, Lukasz Cheng, Allen C. Doolan, Denise L. Matthews, Gail Bond, Katherine Hogarth, P. Mark McQuilten, Zoe Subbarao, Kanta Kedzierska, Katherine Juno, Jennifer A. Wheatley, Adam K. Kent, Stephen J. Williamson, Deborah A. Purcell, Damian F.J. Anderson, David A. Godfrey, Dale I. |
author_facet | Fulford, Thomas S. Van, Huy Gherardin, Nicholas A. Zheng, Shuning Ciula, Marcin Drummer, Heidi E. Redmond, Samuel Tan, Hyon-Xhi Boo, Irene Center, Rob J. Li, Fan Grimley, Samantha L. Wines, Bruce D. Nguyen, Thi H.O. Mordant, Francesca L. Ellenberg, Paula Rowntree, Louise C. Kedzierski, Lukasz Cheng, Allen C. Doolan, Denise L. Matthews, Gail Bond, Katherine Hogarth, P. Mark McQuilten, Zoe Subbarao, Kanta Kedzierska, Katherine Juno, Jennifer A. Wheatley, Adam K. Kent, Stephen J. Williamson, Deborah A. Purcell, Damian F.J. Anderson, David A. Godfrey, Dale I. |
author_sort | Fulford, Thomas S. |
collection | PubMed |
description | BACKGROUND: As vaccines against SARS-CoV-2 are now being rolled out, a better understanding of immunity to the virus, whether from infection, or passive or active immunisation, and the durability of this protection is required. This will benefit from the ability to measure antibody-based protection to SARS-CoV-2, ideally with rapid turnaround and without the need for laboratory-based testing. METHODS: We have developed a lateral flow POC test that can measure levels of RBD-ACE2 neutralising antibody (NAb) from whole blood, with a result that can be determined by eye or quantitatively on a small instrument. We compared our lateral flow test with the gold-standard microneutralisation assay, using samples from convalescent and vaccinated donors, as well as immunised macaques. FINDINGS: We show a high correlation between our lateral flow test with conventional neutralisation and that this test is applicable with animal samples. We also show that this assay is readily adaptable to test for protection to newly emerging SARS-CoV-2 variants, including the beta variant which revealed a marked reduction in NAb activity. Lastly, using a cohort of vaccinated humans, we demonstrate that our whole-blood test correlates closely with microneutralisation assay data (specificity 100% and sensitivity 96% at a microneutralisation cutoff of 1:40) and that fingerprick whole blood samples are sufficient for this test. INTERPRETATION: Taken together, the COVID-19 NAb-test(TM) device described here provides a rapid readout of NAb based protection to SARS-CoV-2 at the point of care. FUNDING: Support was received from the Victorian Operational Infrastructure Support Program and the Australian Government Department of Health. This work was supported by grants from the Department of Health and Human Services of the Victorian State Government; the ARC (CE140100011, CE140100036), the NHMRC (1113293, 2002317 and 1116530), and Medical Research Future Fund Awards (2005544, 2002073, 2002132). Individual researchers were supported by an NHMRC Emerging Leadership Level 1 Investigator Grants (1194036), NHMRC APPRISE Research Fellowship (1116530), NHMRC Leadership Investigator Grant (1173871), NHMRC Principal Research Fellowship (1137285), NHMRC Investigator Grants (1177174 and 1174555) and NHMRC Senior Principal Research Fellowships (1117766 and 1136322). Grateful support was also received from the A2 Milk Company and the Jack Ma Foundation. |
format | Online Article Text |
id | pubmed-8641961 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-86419612021-12-06 A point-of-care lateral flow assay for neutralising antibodies against SARS-CoV-2 Fulford, Thomas S. Van, Huy Gherardin, Nicholas A. Zheng, Shuning Ciula, Marcin Drummer, Heidi E. Redmond, Samuel Tan, Hyon-Xhi Boo, Irene Center, Rob J. Li, Fan Grimley, Samantha L. Wines, Bruce D. Nguyen, Thi H.O. Mordant, Francesca L. Ellenberg, Paula Rowntree, Louise C. Kedzierski, Lukasz Cheng, Allen C. Doolan, Denise L. Matthews, Gail Bond, Katherine Hogarth, P. Mark McQuilten, Zoe Subbarao, Kanta Kedzierska, Katherine Juno, Jennifer A. Wheatley, Adam K. Kent, Stephen J. Williamson, Deborah A. Purcell, Damian F.J. Anderson, David A. Godfrey, Dale I. EBioMedicine Research paper BACKGROUND: As vaccines against SARS-CoV-2 are now being rolled out, a better understanding of immunity to the virus, whether from infection, or passive or active immunisation, and the durability of this protection is required. This will benefit from the ability to measure antibody-based protection to SARS-CoV-2, ideally with rapid turnaround and without the need for laboratory-based testing. METHODS: We have developed a lateral flow POC test that can measure levels of RBD-ACE2 neutralising antibody (NAb) from whole blood, with a result that can be determined by eye or quantitatively on a small instrument. We compared our lateral flow test with the gold-standard microneutralisation assay, using samples from convalescent and vaccinated donors, as well as immunised macaques. FINDINGS: We show a high correlation between our lateral flow test with conventional neutralisation and that this test is applicable with animal samples. We also show that this assay is readily adaptable to test for protection to newly emerging SARS-CoV-2 variants, including the beta variant which revealed a marked reduction in NAb activity. Lastly, using a cohort of vaccinated humans, we demonstrate that our whole-blood test correlates closely with microneutralisation assay data (specificity 100% and sensitivity 96% at a microneutralisation cutoff of 1:40) and that fingerprick whole blood samples are sufficient for this test. INTERPRETATION: Taken together, the COVID-19 NAb-test(TM) device described here provides a rapid readout of NAb based protection to SARS-CoV-2 at the point of care. FUNDING: Support was received from the Victorian Operational Infrastructure Support Program and the Australian Government Department of Health. This work was supported by grants from the Department of Health and Human Services of the Victorian State Government; the ARC (CE140100011, CE140100036), the NHMRC (1113293, 2002317 and 1116530), and Medical Research Future Fund Awards (2005544, 2002073, 2002132). Individual researchers were supported by an NHMRC Emerging Leadership Level 1 Investigator Grants (1194036), NHMRC APPRISE Research Fellowship (1116530), NHMRC Leadership Investigator Grant (1173871), NHMRC Principal Research Fellowship (1137285), NHMRC Investigator Grants (1177174 and 1174555) and NHMRC Senior Principal Research Fellowships (1117766 and 1136322). Grateful support was also received from the A2 Milk Company and the Jack Ma Foundation. Elsevier 2021-12-03 /pmc/articles/PMC8641961/ /pubmed/34871960 http://dx.doi.org/10.1016/j.ebiom.2021.103729 Text en © 2021 Published by Elsevier B.V. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research paper Fulford, Thomas S. Van, Huy Gherardin, Nicholas A. Zheng, Shuning Ciula, Marcin Drummer, Heidi E. Redmond, Samuel Tan, Hyon-Xhi Boo, Irene Center, Rob J. Li, Fan Grimley, Samantha L. Wines, Bruce D. Nguyen, Thi H.O. Mordant, Francesca L. Ellenberg, Paula Rowntree, Louise C. Kedzierski, Lukasz Cheng, Allen C. Doolan, Denise L. Matthews, Gail Bond, Katherine Hogarth, P. Mark McQuilten, Zoe Subbarao, Kanta Kedzierska, Katherine Juno, Jennifer A. Wheatley, Adam K. Kent, Stephen J. Williamson, Deborah A. Purcell, Damian F.J. Anderson, David A. Godfrey, Dale I. A point-of-care lateral flow assay for neutralising antibodies against SARS-CoV-2 |
title | A point-of-care lateral flow assay for neutralising antibodies against SARS-CoV-2 |
title_full | A point-of-care lateral flow assay for neutralising antibodies against SARS-CoV-2 |
title_fullStr | A point-of-care lateral flow assay for neutralising antibodies against SARS-CoV-2 |
title_full_unstemmed | A point-of-care lateral flow assay for neutralising antibodies against SARS-CoV-2 |
title_short | A point-of-care lateral flow assay for neutralising antibodies against SARS-CoV-2 |
title_sort | point-of-care lateral flow assay for neutralising antibodies against sars-cov-2 |
topic | Research paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8641961/ https://www.ncbi.nlm.nih.gov/pubmed/34871960 http://dx.doi.org/10.1016/j.ebiom.2021.103729 |
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