Prediction and in vitro verification of potential CTL epitopes conserved among PRRSV-2 strains

Autores
Welner, Simon; Nielsen, Morten; Rasmussen, Michael; Buus, Søren; Jungersen, Gregers; Larsen, Lars Erik
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) is the causative agent of one of the most important porcine diseases with a high impact on animal health, welfare, and production economy. PRRSV exhibits a multitude of immunoevasive strategies that, in combination with a very high mutation rate, has hampered the development of safe and broadly protective vaccines. Aiming at a vaccine inducing an effective cytotoxic T cell response, a bioinformatics approach was taken to identify conserved PRRSV-derived peptides predicted to react broadly with common swine leukocyte antigen (SLA) class I alleles. Briefly, all possible 9- and 10-mer peptides were generated from 104 complete PRRSV type 2 genomes of confirmed high quality, and peptides with high binding affinity to five common SLAs were identified combining the NetMHCpan and positional scanning combinatorial peptide libraries binding predictions. Predicted binders were prioritized according to genomic conservation and SLA coverage using the PopCover algorithm. From this, 53 peptides were acquired for further analysis. Binding affinity and stability of a subset of 101 peptide-SLA combinations were validated in vitro for 4 of the 5 SLAs. Eventually, 23% of the predicted peptide-SLA combinations showed to form complexes with a dissociation half-life ≥30 min. Additionally, combining the two prediction methods proved to be more robust across alleles than either method used alone in terms of predicted-to-observed correlations. In summary, our approach represents a finely tuned epitope prediction pipeline providing a rationally selected ensemble of peptides for future in vivo experiments with pigs expressing the included SLAs.
Fil: Welner, Simon. Technical University of Denmark; Dinamarca
Fil: Nielsen, Morten. Technical University of Denmark; Dinamarca. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Rasmussen, Michael. Universidad de Copenhagen; Dinamarca
Fil: Buus, Søren. Universidad de Copenhagen; Dinamarca
Fil: Jungersen, Gregers. Technical University of Denmark; Dinamarca
Fil: Larsen, Lars Erik. Technical University of Denmark; Dinamarca
Materia
Cytotoxic T Lymphocytes
Netmhcpan
Popcover
Positional Scanning Combinatorial Peptide Library (Pscpl)
Swine Leukocyte Antigen
Vaccine
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/48613
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/48613
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Prediction and in vitro verification of potential CTL epitopes conserved among PRRSV-2 strainsWelner, SimonNielsen, MortenRasmussen, MichaelBuus, SørenJungersen, GregersLarsen, Lars ErikCytotoxic T LymphocytesNetmhcpanPopcoverPositional Scanning Combinatorial Peptide Library (Pscpl)Swine Leukocyte AntigenVaccinehttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) is the causative agent of one of the most important porcine diseases with a high impact on animal health, welfare, and production economy. PRRSV exhibits a multitude of immunoevasive strategies that, in combination with a very high mutation rate, has hampered the development of safe and broadly protective vaccines. Aiming at a vaccine inducing an effective cytotoxic T cell response, a bioinformatics approach was taken to identify conserved PRRSV-derived peptides predicted to react broadly with common swine leukocyte antigen (SLA) class I alleles. Briefly, all possible 9- and 10-mer peptides were generated from 104 complete PRRSV type 2 genomes of confirmed high quality, and peptides with high binding affinity to five common SLAs were identified combining the NetMHCpan and positional scanning combinatorial peptide libraries binding predictions. Predicted binders were prioritized according to genomic conservation and SLA coverage using the PopCover algorithm. From this, 53 peptides were acquired for further analysis. Binding affinity and stability of a subset of 101 peptide-SLA combinations were validated in vitro for 4 of the 5 SLAs. Eventually, 23% of the predicted peptide-SLA combinations showed to form complexes with a dissociation half-life ≥30 min. Additionally, combining the two prediction methods proved to be more robust across alleles than either method used alone in terms of predicted-to-observed correlations. In summary, our approach represents a finely tuned epitope prediction pipeline providing a rationally selected ensemble of peptides for future in vivo experiments with pigs expressing the included SLAs.Fil: Welner, Simon. Technical University of Denmark; DinamarcaFil: Nielsen, Morten. Technical University of Denmark; Dinamarca. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Rasmussen, Michael. Universidad de Copenhagen; DinamarcaFil: Buus, Søren. Universidad de Copenhagen; DinamarcaFil: Jungersen, Gregers. Technical University of Denmark; DinamarcaFil: Larsen, Lars Erik. Technical University of Denmark; DinamarcaSpringer2017-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/48613Welner, Simon; Nielsen, Morten; Rasmussen, Michael; Buus, Søren; Jungersen, Gregers; et al.; Prediction and in vitro verification of potential CTL epitopes conserved among PRRSV-2 strains; Springer; Immunogenetics; 69; 10; 10-2017; 689-7020093-7711CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1007/s00251-017-1004-8info:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007%2Fs00251-017-1004-8info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:20:46Zoai:ri.conicet.gov.ar:11336/48613instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 11:20:46.694CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Prediction and in vitro verification of potential CTL epitopes conserved among PRRSV-2 strains
title Prediction and in vitro verification of potential CTL epitopes conserved among PRRSV-2 strains
spellingShingle Prediction and in vitro verification of potential CTL epitopes conserved among PRRSV-2 strains
Welner, Simon
Cytotoxic T Lymphocytes
Netmhcpan
Popcover
Positional Scanning Combinatorial Peptide Library (Pscpl)
Swine Leukocyte Antigen
Vaccine
title_short Prediction and in vitro verification of potential CTL epitopes conserved among PRRSV-2 strains
title_full Prediction and in vitro verification of potential CTL epitopes conserved among PRRSV-2 strains
title_fullStr Prediction and in vitro verification of potential CTL epitopes conserved among PRRSV-2 strains
title_full_unstemmed Prediction and in vitro verification of potential CTL epitopes conserved among PRRSV-2 strains
title_sort Prediction and in vitro verification of potential CTL epitopes conserved among PRRSV-2 strains
dc.creator.none.fl_str_mv Welner, Simon
Nielsen, Morten
Rasmussen, Michael
Buus, Søren
Jungersen, Gregers
Larsen, Lars Erik
author Welner, Simon
author_facet Welner, Simon
Nielsen, Morten
Rasmussen, Michael
Buus, Søren
Jungersen, Gregers
Larsen, Lars Erik
author_role author
author2 Nielsen, Morten
Rasmussen, Michael
Buus, Søren
Jungersen, Gregers
Larsen, Lars Erik
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Cytotoxic T Lymphocytes
Netmhcpan
Popcover
Positional Scanning Combinatorial Peptide Library (Pscpl)
Swine Leukocyte Antigen
Vaccine
topic Cytotoxic T Lymphocytes
Netmhcpan
Popcover
Positional Scanning Combinatorial Peptide Library (Pscpl)
Swine Leukocyte Antigen
Vaccine
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) is the causative agent of one of the most important porcine diseases with a high impact on animal health, welfare, and production economy. PRRSV exhibits a multitude of immunoevasive strategies that, in combination with a very high mutation rate, has hampered the development of safe and broadly protective vaccines. Aiming at a vaccine inducing an effective cytotoxic T cell response, a bioinformatics approach was taken to identify conserved PRRSV-derived peptides predicted to react broadly with common swine leukocyte antigen (SLA) class I alleles. Briefly, all possible 9- and 10-mer peptides were generated from 104 complete PRRSV type 2 genomes of confirmed high quality, and peptides with high binding affinity to five common SLAs were identified combining the NetMHCpan and positional scanning combinatorial peptide libraries binding predictions. Predicted binders were prioritized according to genomic conservation and SLA coverage using the PopCover algorithm. From this, 53 peptides were acquired for further analysis. Binding affinity and stability of a subset of 101 peptide-SLA combinations were validated in vitro for 4 of the 5 SLAs. Eventually, 23% of the predicted peptide-SLA combinations showed to form complexes with a dissociation half-life ≥30 min. Additionally, combining the two prediction methods proved to be more robust across alleles than either method used alone in terms of predicted-to-observed correlations. In summary, our approach represents a finely tuned epitope prediction pipeline providing a rationally selected ensemble of peptides for future in vivo experiments with pigs expressing the included SLAs.
Fil: Welner, Simon. Technical University of Denmark; Dinamarca
Fil: Nielsen, Morten. Technical University of Denmark; Dinamarca. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Rasmussen, Michael. Universidad de Copenhagen; Dinamarca
Fil: Buus, Søren. Universidad de Copenhagen; Dinamarca
Fil: Jungersen, Gregers. Technical University of Denmark; Dinamarca
Fil: Larsen, Lars Erik. Technical University of Denmark; Dinamarca
description Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) is the causative agent of one of the most important porcine diseases with a high impact on animal health, welfare, and production economy. PRRSV exhibits a multitude of immunoevasive strategies that, in combination with a very high mutation rate, has hampered the development of safe and broadly protective vaccines. Aiming at a vaccine inducing an effective cytotoxic T cell response, a bioinformatics approach was taken to identify conserved PRRSV-derived peptides predicted to react broadly with common swine leukocyte antigen (SLA) class I alleles. Briefly, all possible 9- and 10-mer peptides were generated from 104 complete PRRSV type 2 genomes of confirmed high quality, and peptides with high binding affinity to five common SLAs were identified combining the NetMHCpan and positional scanning combinatorial peptide libraries binding predictions. Predicted binders were prioritized according to genomic conservation and SLA coverage using the PopCover algorithm. From this, 53 peptides were acquired for further analysis. Binding affinity and stability of a subset of 101 peptide-SLA combinations were validated in vitro for 4 of the 5 SLAs. Eventually, 23% of the predicted peptide-SLA combinations showed to form complexes with a dissociation half-life ≥30 min. Additionally, combining the two prediction methods proved to be more robust across alleles than either method used alone in terms of predicted-to-observed correlations. In summary, our approach represents a finely tuned epitope prediction pipeline providing a rationally selected ensemble of peptides for future in vivo experiments with pigs expressing the included SLAs.
publishDate 2017
dc.date.none.fl_str_mv 2017-10
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/48613
Welner, Simon; Nielsen, Morten; Rasmussen, Michael; Buus, Søren; Jungersen, Gregers; et al.; Prediction and in vitro verification of potential CTL epitopes conserved among PRRSV-2 strains; Springer; Immunogenetics; 69; 10; 10-2017; 689-702
0093-7711
CONICET Digital
CONICET
url http://hdl.handle.net/11336/48613
identifier_str_mv Welner, Simon; Nielsen, Morten; Rasmussen, Michael; Buus, Søren; Jungersen, Gregers; et al.; Prediction and in vitro verification of potential CTL epitopes conserved among PRRSV-2 strains; Springer; Immunogenetics; 69; 10; 10-2017; 689-702
0093-7711
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1007/s00251-017-1004-8
info:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007%2Fs00251-017-1004-8
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Springer
publisher.none.fl_str_mv Springer
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.982451

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