Peptide microarrays coupled to machine learning reveal individual epitopes from human antibody responses with neutralizing capabilities against SARS-CoV-2
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Peptide microarrays coupled to machine learning reveal individual epitopes from human antibody responses with neutralizing capabilities against SARS-CoV-2. / 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.
in: EMERG MICROBES INFEC, Jahrgang 11, Nr. 1, 12.2022, S. 1037-1048.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Peptide microarrays coupled to machine learning reveal individual epitopes from human antibody responses with neutralizing capabilities against SARS-CoV-2
AU - Hotop, Sven-Kevin
AU - Reimering, Susanne
AU - Shekhar, Aditya
AU - Asgari, Ehsaneddin
AU - Beutling, Ulrike
AU - Dahlke, Christine
AU - Fathi, Anahita
AU - Khan, Fawad
AU - Lütgehetmann, Marc
AU - Ballmann, Rico
AU - Gerstner, Andreas
AU - Tegge, Werner
AU - Cicin-Sain, Luka
AU - Bilitewski, Ursula
AU - McHardy, Alice C
AU - Brönstrup, Mark
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
KW - Antibodies, Neutralizing
KW - Antibodies, Viral
KW - Antibody Formation
KW - COVID-19
KW - Epitopes
KW - Humans
KW - Machine Learning
KW - Peptides
KW - SARS-CoV-2
KW - Spike Glycoprotein, Coronavirus
U2 - 10.1080/22221751.2022.2057874
DO - 10.1080/22221751.2022.2057874
M3 - SCORING: Journal article
C2 - 35320064
VL - 11
SP - 1037
EP - 1048
JO - EMERG MICROBES INFEC
JF - EMERG MICROBES INFEC
SN - 2222-1751
IS - 1
ER -