Automated and virus variant-programmable surrogate test qualitatively compares to the gold standard SARS-CoV-2 neutralization assay
Danielle W. Ali,
Maggie L. Bartlett,
Christopher D. Heger,
Francisco Ramirez,
Linwood Johnson,
Kevin L. Schully,
Eric D. Laing,
Wei Wang,
Carol D. Weiss,
Emilie Goguet,
Christopher C. Broder,
Stephanie A. Richard,
Nusrat J. Epsi,
Brian Agan,
David Tribble,
Mark P. Simons,
Timothy H. Burgess,
Edward Mitre,
Simon Pollett,
Darci R. Smith
Affiliations
Danielle W. Ali
Microbiology and Immunology Department, Biological Defense Research Directorate, Naval Medical Research Command, Fort Detrick
Maggie L. Bartlett
Microbiology and Immunology Department, Biological Defense Research Directorate, Naval Medical Research Command, Fort Detrick
Christopher D. Heger
ProteinSimple, a Bio-Techne brand
Francisco Ramirez
ProteinSimple, a Bio-Techne brand
Linwood Johnson
Microbiology and Immunology Department, Biological Defense Research Directorate, Naval Medical Research Command, Fort Detrick
Kevin L. Schully
Austere Environments Consortium for Enhanced Sepsis Outcomes (ACESO), Biological Defense Research Directorate, Naval Medical Research Command
Eric D. Laing
Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences
Wei Wang
Center for Biologics Evaluation and Research, U.S. Food and Drug Administration
Carol D. Weiss
Center for Biologics Evaluation and Research, U.S. Food and Drug Administration
Emilie Goguet
Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences
Christopher C. Broder
Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences
Stephanie A. Richard
Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc.
Nusrat J. Epsi
Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc.
Brian Agan
Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences
David Tribble
Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences
Mark P. Simons
Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences
Timothy H. Burgess
Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences
Edward Mitre
Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences
Simon Pollett
Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc.
Darci R. Smith
Microbiology and Immunology Department, Biological Defense Research Directorate, Naval Medical Research Command, Fort Detrick
Abstract The ongoing emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants underscores the need for rapid, adaptable, high-throughput testing. However, assays for neutralizing antibodies, which are a good measure of viral protection, usually require cell culture and either infectious SARS-CoV-2 or pseudotyped viral particles. To circumvent the challenges of cell-based assays, SARS-CoV-2 surrogate virus neutralization tests (sVNTs) measure inhibition of the binding of the spike (S) protein receptor binding domain (RBD) to its receptor, human angiotensin-converting enzyme 2 (hACE2) by neutralizing antibodies. Here we tested a prototype automated microfluidic cartridge-based sVNT platform using SARS-CoV-2 wild-type (WT) and B.1.617.2 (Delta) variant RBDs. This sVNT showed a high correlation with cell-based neutralization assays for biospecimens collected post-COVID-19 vaccination and post-SARS-CoV-2 infection as well as for pre-pandemic SARS-CoV-2 negative sera. Thus, this assay, which takes less than 80 min, is a relatively simple, safe, and accurate alternative to traditional VNTs.
