Identification and validation of 174 COVID-19 vaccine candidate epitopes reveals low performance of common epitope prediction tools

Abstract The outbreak of SARS-CoV-2 (2019-nCoV) virus has highlighted the need for fast and efficacious vaccine development. Stimulation of a proper immune response that leads to protection is highly dependent on presentation of epitopes to circulating T-cells via the HLA complex. SARS-CoV-2 is a la...

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Autores principales:	Marek Prachar, Sune Justesen, Daniel Bisgaard Steen-Jensen, Stephan Thorgrimsen, Erik Jurgons, Ole Winther, Frederik Otzen Bagger
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2e4f85ebafd44c1a9adb239a6bb78181
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spelling	oai:doaj.org-article:2e4f85ebafd44c1a9adb239a6bb781812021-12-02T15:10:05ZIdentification and validation of 174 COVID-19 vaccine candidate epitopes reveals low performance of common epitope prediction tools10.1038/s41598-020-77466-42045-2322https://doaj.org/article/2e4f85ebafd44c1a9adb239a6bb781812020-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-77466-4https://doaj.org/toc/2045-2322Abstract The outbreak of SARS-CoV-2 (2019-nCoV) virus has highlighted the need for fast and efficacious vaccine development. Stimulation of a proper immune response that leads to protection is highly dependent on presentation of epitopes to circulating T-cells via the HLA complex. SARS-CoV-2 is a large RNA virus and testing of all of its overlapping peptides in vitro to deconvolute an immune response is not feasible. Therefore HLA-binding prediction tools are often used to narrow down the number of peptides to test. We tested NetMHC suite tools' predictions by using an in vitro peptide-MHC stability assay. We assessed 777 peptides that were predicted to be good binders across 11 MHC alleles in a complex-stability assay and tested a selection of 19 epitope-HLA-binding prediction tools against the assay. In this investigation of potential SARS-CoV-2 epitopes we found that current prediction tools vary in performance when assessing binding stability, and they are highly dependent on the MHC allele in question. Designing a COVID-19 vaccine where only a few epitope targets are included is therefore a very challenging task. Here, we present 174 SARS-CoV-2 epitopes with high prediction binding scores, validated to bind stably to 11 HLA alleles. Our findings may contribute to the design of an efficacious vaccine against COVID-19.Marek PracharSune JustesenDaniel Bisgaard Steen-JensenStephan ThorgrimsenErik JurgonsOle WintherFrederik Otzen BaggerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-8 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Marek Prachar Sune Justesen Daniel Bisgaard Steen-Jensen Stephan Thorgrimsen Erik Jurgons Ole Winther Frederik Otzen Bagger Identification and validation of 174 COVID-19 vaccine candidate epitopes reveals low performance of common epitope prediction tools
description	Abstract The outbreak of SARS-CoV-2 (2019-nCoV) virus has highlighted the need for fast and efficacious vaccine development. Stimulation of a proper immune response that leads to protection is highly dependent on presentation of epitopes to circulating T-cells via the HLA complex. SARS-CoV-2 is a large RNA virus and testing of all of its overlapping peptides in vitro to deconvolute an immune response is not feasible. Therefore HLA-binding prediction tools are often used to narrow down the number of peptides to test. We tested NetMHC suite tools' predictions by using an in vitro peptide-MHC stability assay. We assessed 777 peptides that were predicted to be good binders across 11 MHC alleles in a complex-stability assay and tested a selection of 19 epitope-HLA-binding prediction tools against the assay. In this investigation of potential SARS-CoV-2 epitopes we found that current prediction tools vary in performance when assessing binding stability, and they are highly dependent on the MHC allele in question. Designing a COVID-19 vaccine where only a few epitope targets are included is therefore a very challenging task. Here, we present 174 SARS-CoV-2 epitopes with high prediction binding scores, validated to bind stably to 11 HLA alleles. Our findings may contribute to the design of an efficacious vaccine against COVID-19.
format	article
author	Marek Prachar Sune Justesen Daniel Bisgaard Steen-Jensen Stephan Thorgrimsen Erik Jurgons Ole Winther Frederik Otzen Bagger
author_facet	Marek Prachar Sune Justesen Daniel Bisgaard Steen-Jensen Stephan Thorgrimsen Erik Jurgons Ole Winther Frederik Otzen Bagger
author_sort	Marek Prachar
title	Identification and validation of 174 COVID-19 vaccine candidate epitopes reveals low performance of common epitope prediction tools
title_short	Identification and validation of 174 COVID-19 vaccine candidate epitopes reveals low performance of common epitope prediction tools
title_full	Identification and validation of 174 COVID-19 vaccine candidate epitopes reveals low performance of common epitope prediction tools
title_fullStr	Identification and validation of 174 COVID-19 vaccine candidate epitopes reveals low performance of common epitope prediction tools
title_full_unstemmed	Identification and validation of 174 COVID-19 vaccine candidate epitopes reveals low performance of common epitope prediction tools
title_sort	identification and validation of 174 covid-19 vaccine candidate epitopes reveals low performance of common epitope prediction tools
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/2e4f85ebafd44c1a9adb239a6bb78181
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Identification and validation of 174 COVID-19 vaccine candidate epitopes reveals low performance of common epitope prediction tools

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