TY - JOUR
T1 - A point-of-care lateral flow assay for neutralising antibodies against SARS-CoV-2
AU - Fulford, Thomas S.
AU - Van, Huy
AU - Gherardin, Nicholas A.
AU - Zheng, Shuning
AU - Ciula, Marcin
AU - Drummer, Heidi E.
AU - Redmond, Samuel
AU - Tan, Hyon Xhi
AU - Boo, Irene
AU - Center, Rob J.
AU - Li, Fan
AU - Grimley, Samantha L.
AU - Wines, Bruce D.
AU - Nguyen, Thi H.O.
AU - Mordant, Francesca L.
AU - Ellenberg, Paula
AU - Rowntree, Louise C.
AU - Kedzierski, Lukasz
AU - Cheng, Allen C.
AU - Doolan, Denise L.
AU - Matthews, Gail
AU - Bond, Katherine
AU - Hogarth, P. Mark
AU - McQuilten, Zoe
AU - Subbarao, Kanta
AU - Kedzierska, Katherine
AU - Juno, Jennifer A.
AU - Wheatley, Adam K.
AU - Kent, Stephen J.
AU - Williamson, Deborah A.
AU - Purcell, Damian F.J.
AU - Anderson, David A.
AU - Godfrey, Dale I.
N1 - Funding Information:
We are grateful to the volunteers who provided samples for study. The authors would like to thank the Australian Red Cross Lifeblood for the supply of specimens from COVID-19 convalescent plasma donors and ‘pre-COVID’ controls. Australian Governments fund the Australian Red Cross Lifeblood to provide blood, blood products and services to the Australian community. The authors gratefully acknowledge the contribution to this work of the Victorian Operational Infrastructure Support Program received by the Burnet Institute. This work was supported by grants from the Department of Health and Human Services (DHHS) of the Victorian State Government; the Australian Research Council (ARC; CE140100011, CE140100036) the National Health and Medical Research Council of Australia (NHMRC; 1113293, 2002317 and 1116530), and Medical Research Future Fund (MRFF) Awards (2005544, 2002073, 2002132). THON and AKW were supported by an NHMRC Emerging Leadership Level 1 Investigator Grants (1194036), HV was supported by an NHMRC APPRISE Research Fellowship (1116530), KK was supported by the NHMRC Leadership Investigator Grant (1173871), DLL was supported by a NHMRC Principal Research Fellowship (1137285), KS and DAW are supported by NHMRC Investigator Grants (1177174 and 1174555). KS also received support from the A2 Milk Company and KS, DP and DG received support from the Jack Ma Foundation. The Melbourne WHO Collaborating Centre for Reference and Research on Influenza is supported by the Australian Government Department of Health. DIG and SJK were supported by NHMRC Senior Principal Research Fellowships (1117766 and 1136322).
Funding Information:
Dr. Fulford reports a patent Australian Provisional Patent Application 2021901011 (filed 7 April 2021) “Point of care lateral flow test for COVID19 detection” pending. Mr. Van reports grants from Government of the State of Victoria, during the conduct of the study; In addition, Mr. Van has a patent Australian Provisional Patent Application 2021901011 (filed 7 April 2021) “Point of care lateral flow test for COVID19 detection” pending. Dr. Gherardin reports a patent Australian Provisional Patent Application 2021901011 (filed 7 April 2021) “Point of care lateral flow test for COVID19 detection” pending. Ms. Zheng reports grants from Government of the State of Victoria, during the conduct of the study; In addition, Ms. Zheng has a patent Australian Provisional Patent Application 2021901011 (filed 7 April 2021) “Point of care lateral flow test for COVID19 detection” pending. Mr. Ciula has nothing to disclose. Prof. Drummer has nothing to disclose. Mr. Redmond has nothing to disclose. Dr. Tan has nothing to disclose. Ms. Boo has nothing to disclose. Dr. Center has nothing to disclose. Dr. Li has nothing to disclose. Dr. Grimley has nothing to disclose. Dr. Wines reports grants from Australian Govt, Medical Research Future Fund, grants from NHMRC, National Health and Medical Research Council GNT1145303, Australia, during the conduct of the study; In addition, Dr. Wines has a patent drafted for use of ACE2-Fc pending. Dr. Nguyen has nothing to disclose. Ms. Mordant has nothing to disclose. Dr. Ellenberg has nothing to disclose. Dr. Rowntree has nothing to disclose. Lukasz Kedzierski has nothing to disclose. Prof. Cheng reports that he is a member of government advisory committees advising on COVID policy. Prof. Doolan has nothing to disclose. Prof. Matthews reports grants from Curran Foundation, during the conduct of the study; grants from Gilead sciences, grants from Abbvie Inc outside the submitted work. Dr. Bond has nothing to disclose. Prof. Hogarth reports grants from NHMRC, grants from MRFF, during the conduct of the study; In addition, Prof. Hogarth has a patent Antiviral pending. A/Prof. McQuilten reports grants from Medical Research Future Fund, during the conduct of the study. Prof. Subbarao has nothing to disclose. Prof. Kedzierska has nothing to disclose. Dr. Juno has nothing to disclose. Dr. Wheatley has nothing to disclose. Prof. Kent has nothing to disclose. Prof. Williamson has nothing to disclose. Prof. Purcell reports grants from Victorian Government DHHS, grants from Medical Research Future Fund, other from Jack Ma Foundation, during the conduct of the study; In addition, Prof. Purcell has a patent PCT/AU2021/050839 pending. Prof. Anderson reports grants from Government of the State of Victoria, during the conduct of the study; other from Nanjing BioPoint Diagnostic Technology, outside the submitted work; In addition, Prof. Anderson has a patent Australian Provisional Patent Application 2021901011 (filed 7 April 2021) “Point of care lateral flow test for COVID19 detection” pending. Prof. Godfrey reports grants from Victorian Government DHHS, and from Australian Research Council, during the conduct of the study; grants from Medical Research Future Fund, other from Jack Ma Foundation, grants from National Health and Medical Research Council, outside the submitted work; In addition, Prof. Godfrey has a patent Australian Provisional Patent Application 2021901011 (filed 7 April 2021) “Point of care lateral flow test for COVID19 detection” pending.
Publisher Copyright:
© 2021
PY - 2021/12
Y1 - 2021/12
N2 - 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-testTM 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.
AB - 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-testTM 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.
KW - Lateral flow assay
KW - Neturalising antibodies
KW - Point of care test
KW - SARS-CoV-2
UR - http://www.scopus.com/inward/record.url?scp=85120496986&partnerID=8YFLogxK
U2 - 10.1016/j.ebiom.2021.103729
DO - 10.1016/j.ebiom.2021.103729
M3 - Article
C2 - 34871960
AN - SCOPUS:85120496986
SN - 2352-3964
VL - 74
JO - EBioMedicine
JF - EBioMedicine
M1 - 103729
ER -
