An Approach for a Synthetic CTL Vaccine Design against Zika Flavivrus Using Class I and Class II Epitopes Identified by Computer Modeling

Detalhes bibliográficos
Autor(a) principal: Cunha-Neto, Edecio
Data de Publicação: 2017
Outros Autores: Rosa, Daniela S. [UNIFESP], Harris, Paul E., Olson, Tim, Morrow, Alex, Ciotlos, Serban, Herst, Charles V., Rubsamen, Reid Martin
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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spelling 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