Evaluation of a multi-species SARS-CoV-2 surrogate virus neutralization test
Carmen W.E. Embregts,
Babs Verstrepen,
Jan A.M. Langermans,
Kinga P. Böszörményi,
Reina S. Sikkema,
Rory D. de Vries,
Donata Hoffmann,
Kerstin Wernike,
Lidwien A.M. Smit,
Shan Zhao,
Barry Rockx,
Marion P.G. Koopmans,
Bart L. Haagmans,
Thijs Kuiken,
Corine H. GeurtsvanKessel
Affiliations
Carmen W.E. Embregts
Department of Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands; Corresponding authors.
Babs Verstrepen
Biomedical Primate Research Centre, Rijswijk, the Netherlands
Jan A.M. Langermans
Biomedical Primate Research Centre, Rijswijk, the Netherlands; Department Population Health Sciences, Division Animals in Science and Society, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands
Kinga P. Böszörményi
Biomedical Primate Research Centre, Rijswijk, the Netherlands
Reina S. Sikkema
Department of Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands
Rory D. de Vries
Department of Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands
Donata Hoffmann
Institute of Diagnostic Virology, Friedrich-Loeffler-Institute, Insel Riems, Germany
Kerstin Wernike
Institute of Diagnostic Virology, Friedrich-Loeffler-Institute, Insel Riems, Germany
Lidwien A.M. Smit
Institute for Risk Assessment Sciences, Utrecht University, Utrecht, the Netherlands
Shan Zhao
Department of Biomolecular Health Sciences, Virology Division, Faculty of Veterinary Medicine, Utrecht University, the Netherlands
Barry Rockx
Department of Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands
Marion P.G. Koopmans
Department of Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands
Bart L. Haagmans
Department of Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands
Thijs Kuiken
Department of Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands
Corine H. GeurtsvanKessel
Department of Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands; Corresponding authors.
Assays to measure SARS-CoV-2-specific neutralizing antibodies are important to monitor seroprevalence, to study asymptomatic infections and to reveal (intermediate) hosts. A recently developed assay, the surrogate virus-neutralization test (sVNT) is a quick and commercially available alternative to the “gold standard” virus neutralization assay using authentic virus, and does not require processing at BSL-3 level. The assay relies on the inhibition of binding of the receptor binding domain (RBD) on the spike (S) protein to human angiotensin-converting enzyme 2 (hACE2) by antibodies present in sera. As the sVNT does not require species- or isotype-specific conjugates, it can be similarly used for antibody detection in human and animal sera. In this study, we used 298 sera from PCR-confirmed COVID-19 patients and 151 sera from patients confirmed with other coronavirus or other (respiratory) infections, to evaluate the performance of the sVNT. To analyze the use of the assay in a One Health setting, we studied the presence of RBD-binding antibodies in 154 sera from nine animal species (cynomolgus and rhesus macaques, ferrets, rabbits, hamsters, cats, cattle, mink and dromedary camels). The sVNT showed a moderate to high sensitivity and a high specificity using sera from confirmed COVID-19 patients (91.3% and 100%, respectively) and animal sera (93.9% and 100%), however it lacked sensitivity to detect low titers. Significant correlations were found between the sVNT outcomes and PRNT50 and the Wantai total Ig and IgM ELISAs. While species-specific validation will be essential, our results show that the sVNT holds promise in detecting RBD-binding antibodies in multiple species.
