Peptide microarrays coupled to machine learning reveal individual epitopes from human antibody responses with neutralizing capabilities against SARS-CoV-2

verfasst von
Sven Kevin Hotop, Susanne Reimering, Aditya Shekhar, Ehsaneddin Asgari, Ulrike Beutling, Christine Dahlke, Anahita Fathi, Fawad Khan, Marc Lütgehetmann, Rico Ballmann, Andreas Gerstner, Werner Tegge, Luka Cicin-Sain, Ursula Bilitewski, Alice C. McHardy, Mark Brönstrup
Abstract

The coronavirus SARS-CoV-2 is the causative agent for the disease COVID-19. To capture the IgA, IgG, and IgM antibody response of patients infected with SARS-CoV-2 at individual epitope resolution, we constructed planar microarrays of 648 overlapping peptides that cover the four major structural proteins S(pike), N(ucleocapsid), M(embrane), and E(nvelope). The arrays were incubated with sera of 67 SARS-CoV-2 positive and 22 negative control samples. Specific responses to SARS-CoV-2 were detectable, and nine peptides were associated with a more severe course of the disease. A random forest model disclosed that antibody binding to 21 peptides, mostly localized in the S protein, was associated with higher neutralization values in cellular anti-SARS-CoV-2 assays. For antibodies addressing the N-terminus of M, or peptides close to the fusion region of S, protective effects were proven by antibody depletion and neutralization assays. The study pinpoints unusual viral binding epitopes that might be suited as vaccine candidates.

Organisationseinheit(en)
Zentrum für Biomolekulare Wirkstoffe (BMWZ)
Externe Organisation(en)
Helmholtz-Zentrum für Infektionsforschung GmbH (HZI)
Technische Universität Braunschweig
Universität Hamburg
Bernhard-Nocht-Institut für Tropenmedizin (BNITM)
Deutsches Zentrum für Infektionsforschung (DZIF)
Städtisches Klinikum Braunschweig
Typ
Artikel
Journal
Emerging Microbes and Infections
Band
11
Seiten
1037-1048
Anzahl der Seiten
12
ISSN
2222-1751
Publikationsdatum
2022
Publikationsstatus
Veröffentlicht
Peer-reviewed
Ja
ASJC Scopus Sachgebiete
Parasitologie, Epidemiologie, Mikrobiologie, Immunologie, Wirkstoffforschung, Virologie, Infektionskrankheiten
Ziele für nachhaltige Entwicklung
SDG 3 – Gute Gesundheit und Wohlergehen
Elektronische Version(en)
https://doi.org/10.1080/22221751.2022.2057874 (Zugang: Offen)