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NeutrobodyPlex-monitoring SARS-CoV-2 neutralizing immune responses using nanobodies.
Wagner, Teresa R Ostertag, Elena Kaiser, Philipp D Gramlich, Marius Ruetalo, Natalia Junker, Daniel Haering, Julia Traenkle, Bjoern Becker, Matthias Dulovic, Alex
Wagner, Teresa R
Ostertag, Elena
Kaiser, Philipp D
Gramlich, Marius
Ruetalo, Natalia
Junker, Daniel
Haering, Julia
Traenkle, Bjoern
Becker, Matthias
Dulovic, Alex
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2021-04-27
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Abstract
In light of the COVID-19 pandemic, there is an ongoing need for diagnostic tools to monitor the immune status of large patient cohorts and the effectiveness of vaccination campaigns. Here, we present 11 unique nanobodies (Nbs) specific for the SARS-CoV-2 spike receptor-binding domain (RBD), of which 8 Nbs potently inhibit the interaction of RBD with angiotensin-converting enzyme 2 (ACE2) as the major viral docking site. Following detailed epitope mapping and structural analysis, we select two inhibitory Nbs, one of which binds an epitope inside and one of which binds an epitope outside the RBD:ACE2 interface. Based on these, we generate a biparatopic nanobody (bipNb) with viral neutralization efficacy in the picomolar range. Using bipNb as a surrogate, we establish a competitive multiplex binding assay ("NeutrobodyPlex") for detailed analysis of the presence and performance of neutralizing RBD-binding antibodies in serum of convalescent or vaccinated patients. We demonstrate that NeutrobodyPlex enables high-throughput screening and detailed analysis of neutralizing immune responses in infected or vaccinated individuals, to monitor immune status or to guide vaccine design.
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EMBO Rep. 2021 May 5;22(5):e52325. doi: 10.15252/embr.202052325. Epub 2021 Apr 27.
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en
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1469-3178
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Attribution 4.0 International