NeutrobodyPlex-monitoring SARS-CoV-2 neutralizing immune responses using nanobodies.
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Authors
Wagner, Teresa ROstertag, Elena
Kaiser, Philipp D
Gramlich, Marius
Ruetalo, Natalia
Junker, Daniel
Haering, Julia
Traenkle, Bjoern
Becker, Matthias
Dulovic, Alex
Schweizer, Helen
Nueske, Stefan
Scholz, Armin
Zeck, Anne
Schenke-Layland, Katja
Nelde, Annika
Strengert, Monika
Walz, Juliane S
Zocher, Georg
Stehle, Thilo
Schindler, Michael
Schneiderhan-Marra, Nicole
Rothbauer, Ulrich
Issue Date
2021-04-27
Metadata
Show full item recordAbstract
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.Citation
EMBO Rep. 2021 May 5;22(5):e52325. doi: 10.15252/embr.202052325. Epub 2021 Apr 27.Affiliation
TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany.Publisher
EMBO PressJournal
EMBO reportsPubMed ID
33904225Type
ArticleLanguage
enEISSN
1469-3178ae974a485f413a2113503eed53cd6c53
10.15252/embr.202052325
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The following license files are associated with this item:
- Creative Commons
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