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Viral epitope profiling of COVID-19 patients reveals cross-reactivity and correlates of severity.

ABSTRACT: Understanding humoral responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for improving diagnostics, therapeutics, and vaccines. Deep serological profiling of 232 coronavirus disease 2019 (COVID-19) patients and 190 pre-COVID-19 era controls using VirScan revealed more than 800 epitopes in the SARS-CoV-2 proteome, including 10 epitopes likely recognized by neutralizing antibodies. Preexisting antibodies in controls recognized SARS-CoV-2 ORF1, whereas only COVID-19 patient antibodies primarily recognized spike protein and nucleoprotein. A machine learning model trained on VirScan data predicted SARS-CoV-2 exposure history with 99% sensitivity and 98% specificity; a rapid Luminex-based diagnostic was developed from the most discriminatory SARS-CoV-2 peptides. Individuals with more severe COVID-19 exhibited stronger and broader SARS-CoV-2 responses, weaker antibody responses to prior infections, and higher incidence of cytomegalovirus and herpes simplex virus 1, possibly influenced by demographic covariates. Among hospitalized patients, males produce stronger SARS-CoV-2 antibody responses than females.

SUBMITTER: Shrock E

PROVIDER: S-EPMC7857405 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Viral epitope profiling of COVID-19 patients reveals cross-reactivity and correlates of severity.

Shrock Ellen E Fujimura Eric E Kula Tomasz T Timms Richard T RT Lee I-Hsiu IH Leng Yumei Y Robinson Matthew L ML Sie Brandon M BM Li Mamie Z MZ Chen Yuezhou Y Logue Jennifer J Zuiani Adam A McCulloch Denise D Lelis Felipe J N FJN Henson Stephanie S Monaco Daniel R DR Travers Meghan M Habibi Shaghayegh S Clarke William A WA Caturegli Patrizio P Laeyendecker Oliver O Piechocka-Trocha Alicja A Li Jonathan Z JZ Khatri Ashok A Chu Helen Y HY Villani Alexandra-Chloé AC Kays Kyle K Goldberg Marcia B MB Hacohen Nir N Filbin Michael R MR Yu Xu G XG Walker Bruce D BD Wesemann Duane R DR Larman H Benjamin HB Lederer James A JA Elledge Stephen J SJ

Science (New York, N.Y.) 20200929 6520

Understanding humoral responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for improving diagnostics, therapeutics, and vaccines. Deep serological profiling of 232 coronavirus disease 2019 (COVID-19) patients and 190 pre-COVID-19 era controls using VirScan revealed more than 800 epitopes in the SARS-CoV-2 proteome, including 10 epitopes likely recognized by neutralizing antibodies. Preexisting antibodies in controls recognized SARS-CoV-2 ORF1, whereas only COVID- ...[more]

PMID: 32994364

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Project description:Antibodies play an important part in combating SARS‐CoV‐2 infection whether generated by the infection or vaccination. However, the many epitopes generated by infection have not been fully investigated with only a few epitopes known and these being mostly limited to the S protein’s receptor binding domain (RBD) and the N‐terminal domain which limits vaccine and drug design 1‐4. The difference between epitopes generated by infection and vaccination has also not been studied. To address this, we employed a SARS‐CoV‐2 proteome microarray to screen for linear epitopes recognized by antibodies present in COVID‐19 patients and individuals vaccinated with the Pfizer‐BioNTech mRNA COVID‐19 Vaccine. The proteome microarray consisted of S, N, and E proteins, as well as spotting peptides that were 15 amino acids in length with overlaps of 5‐amino acids, covering the entire SARS‐CoV‐2 proteome (MN908947.3) (Figure 1). Blood samples were incubated onto the arrays followed by an incubation of fluorescent secondary anti‐human antibodies. Fluorescent intensity data generated and normalized using the Z‐score method and then further analyzed for significance by parametric one‐way ANOVA with Dunnett's post hoc test (COVID‐19 cohort) and repeated measure ANOVAs with Dunnett's post hoc tests (vaccinated cohort). The full‐length S protein showed a significant increase in COVID‐19 patients at around 20‐23 days after symptom onset and vaccinated individuals over all time points in both IgM and IgG antibodies (Figure 2A). Linear mapping of the IgM epitopes revealed a degree of overlap between infected and vaccinated individuals (22.2%; 6/27 total) with both having epitopes in the RBD and fusion peptide (FP) (Figure 2B). Structural mapping on 3D models of the S protein showed that all epitopes where on the surface of the protein and that COVID‐19 generated epitopes have a different pattern than those generated by vaccination (Figure 2C). An Epitope identified in this study with future prospects is epitope S481‐495 from COIVD‐19 patients that partially overlapped the binding site of two neutralizing antibodies previously isolated from COVID‐19 patients, S2H135 and F2B‐2F61, and contacted amino acids that interact with ACE2 receptor6,7. One epitope of note from the vaccinated individuals is epitope S811‐825 which mapped adjacent to the fusion‐peptide proximal region. These epitopes may be helpful in future vaccine and antibody therapy development. 1 Ju, B. et al. Nature 584, 115‐119. 2 Robbiani, D. F. et al. Nature 584, 437‐442. 3 Seydoux, E. et al. bioRxiv. 4 Wu, Y. et al. Science 368, 1274‐1278. 5 Piccoli, L. et al. Cell 183, 1024‐1042 e1021. 6 Casalino, L. et al. ACS Cent Sci 6, 1722‐1734. 7 Wang, Q. et al. Cell 181, 894‐904 e899.

Dataset Information

Viral epitope profiling of COVID-19 patients reveals cross-reactivity and correlates of severity.

Publications

Viral epitope profiling of COVID-19 patients reveals cross-reactivity and correlates of severity.

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