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

doi:10.1038/s44298-024-00083-9

Automated and virus variant-programmable surrogate test qualitatively compares to the gold standard SARS-CoV-2 neutralization assay

Npj Viruses. 2024 Dec 30;2(1):68. doi: 10.1038/s44298-024-00083-9.

Authors

Danielle W Ali¹, Maggie L Bartlett¹, Christopher D Heger², Francisco Ramirez², Linwood Johnson¹, Kevin L Schully³, Eric D Laing⁴, Wei Wang⁵, Carol D Weiss⁵, Emilie Goguet^{4

6}, Christopher C Broder⁴, Stephanie A Richard^{6

7}, Nusrat J Epsi^{6

7}, Brian Agan⁷, David Tribble⁷, Mark P Simons⁷, Timothy H Burgess⁷, Edward Mitre⁴, Simon Pollett^{6

7}, Darci R Smith⁸

Affiliations

¹ Microbiology and Immunology Department, Biological Defense Research Directorate, Naval Medical Research Command, Fort Detrick, Maryland, MD, USA.
² ProteinSimple, a Bio-Techne brand, San Jose, CA, USA.
³ Austere Environments Consortium for Enhanced Sepsis Outcomes (ACESO), Biological Defense Research Directorate, Naval Medical Research Command, Fort Detrick, MD, USA.
⁴ Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
⁵ Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.
⁶ Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA.
⁷ Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
⁸ Microbiology and Immunology Department, Biological Defense Research Directorate, Naval Medical Research Command, Fort Detrick, Maryland, MD, USA. darci.r.smith.civ@health.mil.

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.

Abstract

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