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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/48613
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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 Técnicas2025-09-29T09:51:23Zoai: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:34982025-09-29 09:51:23.841CONICET 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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13.070432 |