scholarly journals Peptide microarray based analysis of antibody responses to SARS‐CoV‐2 identifies unique epitopes with potential for diagnostic test development

Author(s):  
Pavlo Holenya ◽  
Paul Joris Lange ◽  
Ulf Reimer ◽  
Wolfram Woltersdorf ◽  
Thomas Panterodt ◽  
...  
2019 ◽  
Vol 134 (2_suppl) ◽  
pp. 53S-57S ◽  
Author(s):  
Marla Petway ◽  
Laura Anderson ◽  
Rosemary Humes ◽  
Stephanie Sincock ◽  
Wendi Kuhnert-Tallman ◽  
...  

This study describes the efforts and outcomes associated with the establishment of a clinical sample repository during the 2016 Zika virus epidemic. To overcome the challenge of limited access to clinical samples to support diagnostic test development, multiple US Department of Health and Human Services (HHS) agencies formed a partnership to create the HHS Zika Specimen Repository. In 2016-2017, the Biomedical Advanced Research and Development Authority and the Centers for Disease Control and Prevention collected patient specimens (4420 convalescent sera aliquots from 100 donors and 7171 plasma aliquots from 239 donors), confirmed Zika virus test results, assembled 1 panel for molecular testing (n = 25 sets) and 7 panels for serologic testing (n = 92), and distributed the panels to test developers. We manufactured 8 test panels and distributed 74 sets of panels to 32 commercial companies, public health partners, and research institutions. Manufacturers used these panels to generate data that supported 14 US Food and Drug Administration (FDA) emergency use authorizations and 1 FDA approval. To develop a repository that can respond immediately to future disease outbreaks, we recommend that organizations pre-position procedures, resources, and partnerships to optimize each partner’s contribution.


2016 ◽  
Vol 10 (2) ◽  
pp. e0004331 ◽  
Author(s):  
Edith Roset Bahmanyar ◽  
William Cairns Smith ◽  
Patrick Brennan ◽  
Ray Cummings ◽  
Malcolm Duthie ◽  
...  

2021 ◽  
Author(s):  
Stéphane Pelleau ◽  
Tom Woudenberg ◽  
Jason Rosado ◽  
Françoise Donnadieu ◽  
Laura Garcia ◽  
...  

AbstractInfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a complex antibody response that varies by orders of magnitude between individuals and over time. Waning antibody levels lead to reduced sensitivity of serological diagnostic tests over time. This undermines the utility of serological surveillance as the SARS-CoV-2 pandemic progresses into its second year. Here we develop a multiplex serological test for measuring antibodies of three isotypes (IgG, IgM, IgA) to five SARS-CoV-2 antigens (Spike (S), receptor binding domain (RBD), Nucleocapsid (N), Spike subunit 2, Membrane-Envelope fusion) and the Spike proteins of four seasonal coronaviruses. We measure antibody responses in several cohorts of French and Irish hospitalized patients and healthcare workers followed for up to eleven months after symptom onset. The data are analysed with a mathematical model of antibody kinetics to quantify the duration of antibody responses accounting for inter-individual variation. One year after symptoms, we estimate that 36% (95% range: 11%, 94%) of anti-S IgG remains, 31% (9%, 89%) anti-RBD IgG remains, and 7% (1%, 31%) anti-N IgG remains. Antibodies of the IgM isotype waned more rapidly, with 9% (2%, 32%) anti-RBD IgM remaining after one year. Antibodies of the IgA isotype also waned rapidly, with 10% (3%, 38%) anti-RBD IgA remaining after one year. Quantitative measurements of antibody responses were used to train machine learning algorithms for classification of previous infection and estimation of time since infection. The resulting diagnostic test classified previous infections with 99% specificity and 98% (95% confidence interval: 94%, 99%) sensitivity, with no evidence for declining sensitivity over the time scale considered. The diagnostic test also provided accurate classification of time since infection into intervals of 0 – 3 months, 3 – 6 months, and 6 – 12 months. Finally, we present a computational method for serological reconstruction of past SARS-CoV-2 transmission using the data from this test when applied to samples from a single cross-sectional sero-prevalence survey.


2020 ◽  
Author(s):  
Pavlo Holenya ◽  
Paul Joris Lange ◽  
Ulf Reimer ◽  
Wolfram Woltersdorf ◽  
Thomas Panterodt ◽  
...  

SummaryHumoral immunity to the Severe Adult Respiratory Syndrome (SARS) Coronavirus (CoV)-2 is not fully understood yet but may be a crucial factor of immune protection. The possibility of antibody cross-reactivity between SARS-CoV-2 and other human coronaviruses (HCoVs) would have important implications for immune protection but also for the development of specific diagnostic ELISA tests. Using peptide microarrays, n=24 patient samples and n=12 control samples were screened for antibodies against the entire SARS-CoV-2 proteome as well as the Spike (S), Nucleocapsid (N), VME1 (V), R1ab, and Protein 3a (AP3A) of the HCoV strains SARS, MERS, OC43 and 229E. While widespread cross-reactivity was revealed across several immunodominant regions of S and N, IgG binding to several SARS-CoV-2-derived peptides provided statistically significant discrimination between COVID-19 patients and controls. Selected target peptides may serve as capture antigens for future, highly COVID-19-specific diagnostic antibody tests.


2014 ◽  
Vol 52 (10) ◽  
pp. 3755-3762 ◽  
Author(s):  
C. R. Molins ◽  
C. Sexton ◽  
J. W. Young ◽  
L. V. Ashton ◽  
R. Pappert ◽  
...  

Author(s):  
Anna S Heffron ◽  
Sean J McIlwain ◽  
Maya F Amjadi ◽  
David A Baker ◽  
Saniya Khullar ◽  
...  

The search for potential antibody-based diagnostics, vaccines, and therapeutics for pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has focused almost exclusively on the spike (S) and nucleocapsid (N) proteins. Coronavirus membrane (M), ORF3a, and ORF8 proteins are humoral immunogens in other coronaviruses (CoVs) but remain largely uninvestigated for SARS-CoV-2. Here we use ultradense peptide microarray mapping to show that SARS-CoV-2 infection induces robust antibody responses to epitopes throughout the SARS-CoV-2 proteome, particularly in M, in which one epitope achieved excellent diagnostic accuracy. We map 79 B cell epitopes throughout the SARS-CoV-2 proteome and demonstrate that antibodies that develop in response to SARS-CoV-2 infection bind homologous peptide sequences in the six other known human CoVs. We also confirm reactivity against four of our top-ranking epitopes by enzyme-linked immunosorbent assay (ELISA). Illness severity correlated with increased reactivity to nine SARS-CoV-2 epitopes in S, M, N, and ORF3a in our population. Our results demonstrate previously unknown, highly reactive B cell epitopes throughout the full proteome of SARS-CoV-2 and other CoV proteins.


PLoS ONE ◽  
2018 ◽  
Vol 13 (12) ◽  
pp. e0208851 ◽  
Author(s):  
Aekkachai Tuekprakhon ◽  
Orapim Puiprom ◽  
Tadahiro Sasaki ◽  
Johan Michiels ◽  
Koen Bartholomeeusen ◽  
...  

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