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NeutrobodyPlex—monitoring SARS‐CoV‐2 neutralizing immune responses using nanobodies
Author(s) -
Wagner Teresa R,
Ostertag 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,
SchenkeLayland Katja,
Nelde Annika,
Strengert Monika,
Walz Juliane S,
Zocher Georg,
Stehle Thilo,
Schindler Michael,
SchneiderhanMarra Nicole,
Rothbauer Ulrich
Publication year - 2021
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.202052325
Subject(s) - covid-19 , virology , sars virus , biology , immune system , immune escape , neutralizing antibody , computational biology , genetics , virus , medicine , infectious disease (medical specialty) , outbreak , disease , pathology
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.