Protein-Based Immunome Wide Association Studies (PIWAS) for the Discovery of Significant Disease-Associated Antigens

Haynes, Winston; Kamath, Kathy; Waitz, Rebecca; Daugherty, Patrick S.; Shon, John

doi:10.3389/fimmu.2021.625311

Cited by 14 publications

(9 citation statements)

References 54 publications

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“…The published PIWAS method 65 was used to identify antigen and epitope signals against the UniProt reference SARS-CoV-2 proteome ( UP000464024 ). For each sample, approximately 1–3 million 12-mers were obtained from the SERA assay and these were decomposed into constituent 5- and 6-mers.…”

Section: Methodsmentioning

confidence: 99%

Distinguishing features of long COVID identified through immune profiling

Klein,

Wood,

Jaycox

et al. 2023

Nature

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249

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Post-acute infection syndromes may develop after acute viral disease1. Infection with SARS-CoV-2 can result in the development of a post-acute infection syndrome known as long COVID. Individuals with long COVID frequently report unremitting fatigue, post-exertional malaise, and a variety of cognitive and autonomic dysfunctions2–4. However, the biological processes that are associated with the development and persistence of these symptoms are unclear. Here 275 individuals with or without long COVID were enrolled in a cross-sectional study that included multidimensional immune phenotyping and unbiased machine learning methods to identify biological features associated with long COVID. Marked differences were noted in circulating myeloid and lymphocyte populations relative to the matched controls, as well as evidence of exaggerated humoral responses directed against SARS-CoV-2 among participants with long COVID. Furthermore, higher antibody responses directed against non-SARS-CoV-2 viral pathogens were observed among individuals with long COVID, particularly Epstein–Barr virus. Levels of soluble immune mediators and hormones varied among groups, with cortisol levels being lower among participants with long COVID. Integration of immune phenotyping data into unbiased machine learning models identified the key features that are most strongly associated with long COVID status. Collectively, these findings may help to guide future studies into the pathobiology of long COVID and help with developing relevant biomarkers.

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Section: Methodsmentioning

confidence: 99%

Distinguishing features of long COVID identified through immune profiling

Klein,

Wood,

Jaycox

et al. 2023

Nature

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249

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“…Published Protein-based Immunome Wide Association Studies (PIWAS) methodology, which detects linear epitopes based on SERA data, was used to identify antigen and epitope signals against the SARS-CoV-2 proteome (Uniprot reference: UP000464024) ( 24 ). PIWAS analysis was performed on individual samples, with comparisons drawn longitudinally for each participant and among different booster vaccine formulations using a large convenience control cohort (n = 2766) for signal normalization.…”

Section: Methodsmentioning

confidence: 99%

Profiling antibody epitopes induced by mRNA-1273 vaccination and boosters

Girard,

Baum-Jones,

Best

et al. 2024

Front. Immunol.

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BackgroundCharacterizing the antibody epitope profiles of messenger RNA (mRNA)-based vaccines against SARS-CoV-2 can aid in elucidating the mechanisms underlying the antibody-mediated immune responses elicited by these vaccines.MethodsThis study investigated the distinct antibody epitopes toward the SARS-CoV-2 spike (S) protein targeted after a two-dose primary series of mRNA-1273 followed by a booster dose of mRNA-1273 or a variant-updated vaccine among serum samples from clinical trial adult participants.ResultsMultiple S-specific epitopes were targeted after primary vaccination; while signal decreased over time, a booster dose after >6 months largely revived waning antibody signals. Epitope identity also changed after booster vaccination in some subjects, with four new S-specific epitopes detected with stronger signals after boosting than with primary vaccination. Notably, the strength of antibody responses after booster vaccination differed by the exact vaccine formulation, with variant-updated mRNA-1273.211 and mRNA-1273.617.2 booster formulations inducing significantly stronger S-specific signals than a mRNA-1273 booster.ConclusionOverall, these results identify key S-specific epitopes targeted by antibodies induced by mRNA-1273 primary and variant-updated booster vaccination.

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“…Serimmune peptide array for antibody binding specificity. For identification of antibody binding specificities in 74 samples from 69 subjects from Thiès, Senegal (SEN2), the Serum Epitope Repertoire Analysis (SERA) assay used a fully random 12-mer peptide library displayed by bacteria as described previously 21,22 . Escherichia coli was grown to express a library of 8 × 10 10 peptides and antibodies in serum bound to expressed antigen mimic peptides.…”

Section: Rapid Extracellular Antigen Profiling (Reap)mentioning

confidence: 99%

“…Escherichia coli was grown to express a library of 8 × 10 10 peptides and antibodies in serum bound to expressed antigen mimic peptides. The Protein-based Immunome Wide Association Study (PIWAS) algorithm was used to determine associations between immune profiles and exposure to disease, as has been done in previous studies 22 . Peptide motifs representing epitopes or mimotopes of malaria-specific antibodies were discovered using the IMUNE algorithm as previously described 23 .…”

Section: Rapid Extracellular Antigen Profiling (Reap)mentioning

confidence: 99%

“…To test whether the cross-reactivity in malaria endemic regions was related to exposure to other alpha and beta-human coronaviruses, we used bacterially expressed peptide arrays [21][22][23] and yeast expressed protein arrays known as Rapid Exoproteome Antigen Profiling (REAP) 17 to test reactivity to the receptor binding domain (RBD) of human coronaviruses. Linear peptide epitopes tested against bacterial display libraries did not identify substantial binding of malaria-induced antibodies against SARS-CoV-2 peptides (Fig.…”

Section: Lack Of Correlated Cross-reactivity Between Anti-s1 Antibodi...mentioning

confidence: 99%

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Plasmodium infection is associated with cross-reactive antibodies to carbohydrate epitopes on the SARS-CoV-2 Spike protein

Lapidus

Liu

Casanovas‐Massana

et al. 2022

Sci Rep

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Sero-surveillance can monitor and project disease burden and risk. However, SARS-CoV-2 antibody test results can produce false positive results, limiting their efficacy as a sero-surveillance tool. False positive SARS-CoV-2 antibody results are associated with malaria exposure, and understanding this association is essential to interpret sero-surveillance results from malaria-endemic countries. Here, pre-pandemic samples from eight malaria endemic and non-endemic countries and four continents were tested by ELISA to measure SARS-CoV-2 Spike S1 subunit reactivity. Individuals with acute malaria infection generated substantial SARS-CoV-2 reactivity. Cross-reactivity was not associated with reactivity to other human coronaviruses or other SARS-CoV-2 proteins, as measured by peptide and protein arrays. ELISAs with deglycosylated and desialated Spike S1 subunits revealed that cross-reactive antibodies target sialic acid on N-linked glycans of the Spike protein. The functional activity of cross-reactive antibodies measured by neutralization assays showed that cross-reactive antibodies did not neutralize SARS-CoV-2 in vitro. Since routine use of glycosylated or sialated assays could result in false positive SARS-CoV-2 antibody results in malaria endemic regions, which could overestimate exposure and population-level immunity, we explored methods to increase specificity by reducing cross-reactivity. Overestimating population-level exposure to SARS-CoV-2 could lead to underestimates of risk of continued COVID-19 transmission in sub-Saharan Africa.

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Protein-Based Immunome Wide Association Studies (PIWAS) for the Discovery of Significant Disease-Associated Antigens

Cited by 14 publications

References 54 publications

Distinguishing features of long COVID identified through immune profiling

Distinguishing features of long COVID identified through immune profiling

Profiling antibody epitopes induced by mRNA-1273 vaccination and boosters

Plasmodium infection is associated with cross-reactive antibodies to carbohydrate epitopes on the SARS-CoV-2 Spike protein

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