Details
| Original language | English |
|---|---|
| Pages (from-to) | 1037-1048 |
| Number of pages | 12 |
| Journal | Emerging Microbes and Infections |
| Volume | 11 |
| Issue number | 1 |
| Publication status | Published - 2022 |
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.
Keywords
- COVID-19, immunoassays, machine learning, neutralizing antibodies, peptide arrays, SARS CoV-2, serology
ASJC Scopus subject areas
- Immunology and Microbiology(all)
- Parasitology
- Medicine(all)
- Epidemiology
- Immunology and Microbiology(all)
- Microbiology
- Immunology and Microbiology(all)
- Immunology
- Pharmacology, Toxicology and Pharmaceutics(all)
- Drug Discovery
- Immunology and Microbiology(all)
- Virology
- Medicine(all)
- Infectious Diseases
Sustainable Development Goals
Cite this
- Standard
- Harvard
- Apa
- Vancouver
- BibTeX
- RIS
In: Emerging Microbes and Infections, Vol. 11, No. 1, 2022, p. 1037-1048.
Research output: Contribution to journal › Article › Research › peer review
}
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
N1 - Funding Information: The work was funded by a grant from the Ministry of Science and Culture of Lower Saxony in Germany (project 14-76103-184 Corona 13/20) and by the COVID-19 Research Network of the State of Lower Saxony (COFONI) (14-76403-184). The authors thank Michael Hust for providing the SH2029-G6 monoclonal antibody for assay validation. We also thank the HZI peptide facility, in particular Brigitte Kornak, for its peptide synthesis support. SKH, UBE, RB and WT manufactured chips, performed chip experiments and analyzed the data; CD, AF, ML and AG characterized and provided the serum samples; AS, FK performed SARS-CoV-2 neutralization experiments, UBI, LC conceived and supervised SARS-CoV-2 neutralization experiments, SR, EA and AM analyzed the data. MB conceived the study, analyzed the data and wrote the manuscript.
PY - 2022
Y1 - 2022
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 - COVID-19
KW - immunoassays
KW - machine learning
KW - neutralizing antibodies
KW - peptide arrays
KW - SARS CoV-2
KW - serology
UR - http://www.scopus.com/inward/record.url?scp=85128411633&partnerID=8YFLogxK
U2 - 10.1080/22221751.2022.2057874
DO - 10.1080/22221751.2022.2057874
M3 - Article
C2 - 35320064
AN - SCOPUS:85128411633
VL - 11
SP - 1037
EP - 1048
JO - Emerging Microbes and Infections
JF - Emerging Microbes and Infections
SN - 2222-1751
IS - 1
ER -