An Approach for a Synthetic CTL Vaccine Design against Zika Flavivrus Using Class I and Class II Epitopes Identified by Computer Modeling
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
dARK ID: | ark:/48912/001300000r31z |
DOI: | 10.3389/fimmu.2017.00640 |
Texto Completo: | http://dx.doi.org/10.3389/fimmu.2017.00640 https://repositorio.unifesp.br/handle/11600/53664 |
Resumo: | The threat posed by severe congenital abnormalities related to Zika virus (ZKV) infection during pregnancy has turned development of a ZKV vaccine into an emergency. Recent work suggests that the cytotoxic T lymphocyte (CTL) response to infection is an important defense mechanism in response to ZKV. Here, we develop the rationale and strategy for a new approach to developing cytotoxic T lymphocyte (CTL) vaccines for ZKV flavivirus infection. The proposed approach is based on recent studies using a protein structure computer model for HIV epitope selection designed to select epitopes for CTL attack optimized for viruses that exhibit antigenic drift. Because naturally processed and presented human ZKV T cell epitopes have not yet been described, we identified predicted class I peptide sequences on ZKV matching previously identified DNV (Dengue) class I epitopes and by using a Major Histocompatibility Complex (MHC) binding prediction tool. A subset of those met the criteria for optimal CD8+ attack based on physical chemistry parameters determined by analysis of the ZKV protein structure encoded in open source Protein Data File (PDB) format files. We also identified candidate ZKV epitopes predicted to bind promiscuously to multiple HLA class II molecules that could provide help to the CTL responses. This work suggests that a CTL vaccine for ZKV may be possible even if ZKV exhibits significant antigenic drift. We have previously described a microsphere-based CTL vaccine platform capable of eliciting an immune response for class I epitopes in mice and are currently working toward in vivo testing of class I and class II epitope delivery directed against ZKV epitopes using the same microsphere-based vaccine. |
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An Approach for a Synthetic CTL Vaccine Design against Zika Flavivrus Using Class I and Class II Epitopes Identified by Computer ModelingZika vaccineepitopeCTL vaccineprotein foldingdengueflaviviruscomputer modelThe threat posed by severe congenital abnormalities related to Zika virus (ZKV) infection during pregnancy has turned development of a ZKV vaccine into an emergency. Recent work suggests that the cytotoxic T lymphocyte (CTL) response to infection is an important defense mechanism in response to ZKV. Here, we develop the rationale and strategy for a new approach to developing cytotoxic T lymphocyte (CTL) vaccines for ZKV flavivirus infection. The proposed approach is based on recent studies using a protein structure computer model for HIV epitope selection designed to select epitopes for CTL attack optimized for viruses that exhibit antigenic drift. Because naturally processed and presented human ZKV T cell epitopes have not yet been described, we identified predicted class I peptide sequences on ZKV matching previously identified DNV (Dengue) class I epitopes and by using a Major Histocompatibility Complex (MHC) binding prediction tool. A subset of those met the criteria for optimal CD8+ attack based on physical chemistry parameters determined by analysis of the ZKV protein structure encoded in open source Protein Data File (PDB) format files. We also identified candidate ZKV epitopes predicted to bind promiscuously to multiple HLA class II molecules that could provide help to the CTL responses. This work suggests that a CTL vaccine for ZKV may be possible even if ZKV exhibits significant antigenic drift. We have previously described a microsphere-based CTL vaccine platform capable of eliciting an immune response for class I epitopes in mice and are currently working toward in vivo testing of class I and class II epitope delivery directed against ZKV epitopes using the same microsphere-based vaccine.Univ Sao Paulo, Sch Med, Lab Clin Immunol & Allergy LIM60, Sao Paulo, BrazilInst Invest Immunol III INCT, Sao Paulo, BrazilUniv Sao Paulo, Heart Inst Incor, Sch Med, Sao Paulo, BrazilFed Univ Sao Paulo UNIFESP EPM, Dept Microbiol Immunol & Parasitol, Sao Paulo, BrazilColumbia Univ, Dept Med, Sch Med, Endocrinol Div, New York, NY USAMorrow, AlexCiotlos, SerbanFlow Pharma Inc, Redwood City, CA 94063 USAMassachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USAUniv Fed Sao Paulo UNIFESP EPM, Dept Microbiol Immunol & Parasitol, Sao Paulo, BrazilWeb of ScienceFlow Pharma, Inc.CNPq (Brazilian National Scientific Council)FAPESP (Sao Paulo State Research Foundation)Flow Pharma, Inc.CNPqFAPESP: 13/50302-3Frontiers Media Sa2020-06-26T16:30:37Z2020-06-26T16:30:37Z2017info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion-application/pdfhttp://dx.doi.org/10.3389/fimmu.2017.00640Frontiers In Immunology. Lausanne, v. 8, p. -, 2017.10.3389/fimmu.2017.00640WOS000402910200001.pdf1664-3224https://repositorio.unifesp.br/handle/11600/53664WOS:000402910200001ark:/48912/001300000r31zengFrontiers In ImmunologyLausanneinfo:eu-repo/semantics/openAccessCunha-Neto, EdecioRosa, Daniela S. [UNIFESP]Harris, Paul E.Olson, TimMorrow, AlexCiotlos, SerbanHerst, Charles V.Rubsamen, Reid Martinreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2024-08-11T01:50:36Zoai:repositorio.unifesp.br/:11600/53664Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652024-12-11T20:32:21.879183Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.none.fl_str_mv |
An Approach for a Synthetic CTL Vaccine Design against Zika Flavivrus Using Class I and Class II Epitopes Identified by Computer Modeling |
title |
An Approach for a Synthetic CTL Vaccine Design against Zika Flavivrus Using Class I and Class II Epitopes Identified by Computer Modeling |
spellingShingle |
An Approach for a Synthetic CTL Vaccine Design against Zika Flavivrus Using Class I and Class II Epitopes Identified by Computer Modeling An Approach for a Synthetic CTL Vaccine Design against Zika Flavivrus Using Class I and Class II Epitopes Identified by Computer Modeling Cunha-Neto, Edecio Zika vaccine epitope CTL vaccine protein folding dengue flavivirus computer model Cunha-Neto, Edecio Zika vaccine epitope CTL vaccine protein folding dengue flavivirus computer model |
title_short |
An Approach for a Synthetic CTL Vaccine Design against Zika Flavivrus Using Class I and Class II Epitopes Identified by Computer Modeling |
title_full |
An Approach for a Synthetic CTL Vaccine Design against Zika Flavivrus Using Class I and Class II Epitopes Identified by Computer Modeling |
title_fullStr |
An Approach for a Synthetic CTL Vaccine Design against Zika Flavivrus Using Class I and Class II Epitopes Identified by Computer Modeling An Approach for a Synthetic CTL Vaccine Design against Zika Flavivrus Using Class I and Class II Epitopes Identified by Computer Modeling |
title_full_unstemmed |
An Approach for a Synthetic CTL Vaccine Design against Zika Flavivrus Using Class I and Class II Epitopes Identified by Computer Modeling An Approach for a Synthetic CTL Vaccine Design against Zika Flavivrus Using Class I and Class II Epitopes Identified by Computer Modeling |
title_sort |
An Approach for a Synthetic CTL Vaccine Design against Zika Flavivrus Using Class I and Class II Epitopes Identified by Computer Modeling |
author |
Cunha-Neto, Edecio |
author_facet |
Cunha-Neto, Edecio Cunha-Neto, Edecio Rosa, Daniela S. [UNIFESP] Harris, Paul E. Olson, Tim Morrow, Alex Ciotlos, Serban Herst, Charles V. Rubsamen, Reid Martin Rosa, Daniela S. [UNIFESP] Harris, Paul E. Olson, Tim Morrow, Alex Ciotlos, Serban Herst, Charles V. Rubsamen, Reid Martin |
author_role |
author |
author2 |
Rosa, Daniela S. [UNIFESP] Harris, Paul E. Olson, Tim Morrow, Alex Ciotlos, Serban Herst, Charles V. Rubsamen, Reid Martin |
author2_role |
author author author author author author author |
dc.contributor.author.fl_str_mv |
Cunha-Neto, Edecio Rosa, Daniela S. [UNIFESP] Harris, Paul E. Olson, Tim Morrow, Alex Ciotlos, Serban Herst, Charles V. Rubsamen, Reid Martin |
dc.subject.por.fl_str_mv |
Zika vaccine epitope CTL vaccine protein folding dengue flavivirus computer model |
topic |
Zika vaccine epitope CTL vaccine protein folding dengue flavivirus computer model |
description |
The threat posed by severe congenital abnormalities related to Zika virus (ZKV) infection during pregnancy has turned development of a ZKV vaccine into an emergency. Recent work suggests that the cytotoxic T lymphocyte (CTL) response to infection is an important defense mechanism in response to ZKV. Here, we develop the rationale and strategy for a new approach to developing cytotoxic T lymphocyte (CTL) vaccines for ZKV flavivirus infection. The proposed approach is based on recent studies using a protein structure computer model for HIV epitope selection designed to select epitopes for CTL attack optimized for viruses that exhibit antigenic drift. Because naturally processed and presented human ZKV T cell epitopes have not yet been described, we identified predicted class I peptide sequences on ZKV matching previously identified DNV (Dengue) class I epitopes and by using a Major Histocompatibility Complex (MHC) binding prediction tool. A subset of those met the criteria for optimal CD8+ attack based on physical chemistry parameters determined by analysis of the ZKV protein structure encoded in open source Protein Data File (PDB) format files. We also identified candidate ZKV epitopes predicted to bind promiscuously to multiple HLA class II molecules that could provide help to the CTL responses. This work suggests that a CTL vaccine for ZKV may be possible even if ZKV exhibits significant antigenic drift. We have previously described a microsphere-based CTL vaccine platform capable of eliciting an immune response for class I epitopes in mice and are currently working toward in vivo testing of class I and class II epitope delivery directed against ZKV epitopes using the same microsphere-based vaccine. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017 2020-06-26T16:30:37Z 2020-06-26T16:30:37Z |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.3389/fimmu.2017.00640 Frontiers In Immunology. Lausanne, v. 8, p. -, 2017. 10.3389/fimmu.2017.00640 WOS000402910200001.pdf 1664-3224 https://repositorio.unifesp.br/handle/11600/53664 WOS:000402910200001 |
dc.identifier.dark.fl_str_mv |
ark:/48912/001300000r31z |
url |
http://dx.doi.org/10.3389/fimmu.2017.00640 https://repositorio.unifesp.br/handle/11600/53664 |
identifier_str_mv |
Frontiers In Immunology. Lausanne, v. 8, p. -, 2017. 10.3389/fimmu.2017.00640 WOS000402910200001.pdf 1664-3224 WOS:000402910200001 ark:/48912/001300000r31z |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Frontiers In Immunology |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
- application/pdf |
dc.coverage.none.fl_str_mv |
Lausanne |
dc.publisher.none.fl_str_mv |
Frontiers Media Sa |
publisher.none.fl_str_mv |
Frontiers Media Sa |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UNIFESP instname:Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP |
instname_str |
Universidade Federal de São Paulo (UNIFESP) |
instacron_str |
UNIFESP |
institution |
UNIFESP |
reponame_str |
Repositório Institucional da UNIFESP |
collection |
Repositório Institucional da UNIFESP |
repository.name.fl_str_mv |
Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP) |
repository.mail.fl_str_mv |
biblioteca.csp@unifesp.br |
_version_ |
1822219207478083584 |
dc.identifier.doi.none.fl_str_mv |
10.3389/fimmu.2017.00640 |