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)