Peptide microarrays coupled to machine learning reveal individual epitopes from human antibody responses with neutralizing capabilities against SARS-CoV-2. Issue 1 (31st December 2022)

• Record Type: Journal Article
• Authors: Hotop, Sven-Kevin; Reimering, Susanne; Shekhar, Aditya; Asgari, Ehsaneddin; Beutling, Ulrike; Dahlke, Christine; Fathi, Anahita; Khan, Fawad; Lütgehetmann, Marc; Ballmann, Rico; Gerstner, Andreas; Tegge, Werner; Cicin-Sain, Luka; Bilitewski, Ursula; McHardy, Alice C.; Brönstrup, Mark
• Is Part Of: Emerging microbes & infections. Volume 11:Issue 1(2022)
• Page Start: 1037
• Page End: 1048
• Publication Date: 2022-12-31
• Subjects: COVID-19 -- SARS CoV-2 -- immunoassays -- peptide arrays -- serology -- machine learning -- neutralizing antibodies; Medical microbiology -- Periodicals; Communicable diseases -- Periodicals; Infection -- Periodicals; 616.9041
• DOI: 10.1080/22221751.2022.2057874
• Languages: English
• ISSNs: 2222-1751

Abstract

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.