Measuring SARS-CoV-2 neutralizing antibody activity using pseudotyped and chimeric viruses

Fabian Schmidt, Yiska Weisblum, Frauke Muecksch, Hans Heinrich Hoffmann, Eleftherios Michailidis, Julio C.C. Lorenzi, Pilar Mendoza, Magdalena Rutkowska, Eva Bednarski, Christian Gaebler, Marianna Agudelo, Alice Cho, Zijun Wang, Anna Gazumyan, Melissa Cipolla, Marina Caskey, Davide F. Robbiani, Michel C. Nussenzweig, Charles M. Rice, Theodora HatziioannouPaul D. Bieniasz

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350 Scopus citations


The emergence of SARS-CoV-2 and the ensuing explosive epidemic of COVID-19 disease has generated a need for assays to rapidly and conveniently measure the antiviral activity of SARS-CoV-2-specific antibodies. Here, we describe a collection of approaches based on SARS-CoV-2 spike-pseudotyped, single-cycle, replication-defective human immunodeficiency virus type-1 (HIV-1), and vesicular stomatitis virus (VSV), as well as a replication-competent VSV/SARS-CoV-2 chimeric virus. While each surrogate virus exhibited subtle differences in the sensitivity with which neutralizing activity was detected, the neutralizing activity of both convalescent plasma and human monoclonal antibodies measured using each virus correlated quantitatively with neutralizing activity measured using an authentic SARS-CoV-2 neutralization assay. The assays described herein are adaptable to high throughput and are useful tools in the evaluation of serologic immunity conferred by vaccination or prior SARS-CoV-2 infection, as well as the potency of convalescent plasma or human monoclonal antibodies.
Original languageEnglish (US)
JournalJournal of Experimental Medicine
Issue number11
StatePublished - Jul 21 2020
Externally publishedYes


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