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

dc.citation.volume8]
dc.contributor.authorCunha-Neto, Edecio
dc.contributor.authorRosa, Daniela S. [UNIFESP]
dc.contributor.authorHarris, Paul E.
dc.contributor.authorOlson, Tim
dc.contributor.authorMorrow, Alex
dc.contributor.authorCiotlos, Serban
dc.contributor.authorHerst, Charles V.
dc.contributor.authorRubsamen, Reid Martin
dc.coverageLausanne
dc.date.accessioned2020-06-26T16:30:37Z
dc.date.available2020-06-26T16:30:37Z
dc.date.issued2017
dc.description.abstractThe 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.en
dc.description.affiliationUniv Sao Paulo, Sch Med, Lab Clin Immunol & Allergy LIM60, Sao Paulo, Brazil
dc.description.affiliationInst Invest Immunol III INCT, Sao Paulo, Brazil
dc.description.affiliationUniv Sao Paulo, Heart Inst Incor, Sch Med, Sao Paulo, Brazil
dc.description.affiliationFed Univ Sao Paulo UNIFESP EPM, Dept Microbiol Immunol & Parasitol, Sao Paulo, Brazil
dc.description.affiliationColumbia Univ, Dept Med, Sch Med, Endocrinol Div, New York, NY USA
dc.description.affiliationMorrow, Alex
dc.description.affiliationCiotlos, Serban
dc.description.affiliationFlow Pharma Inc, Redwood City, CA 94063 USA
dc.description.affiliationMassachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA
dc.description.affiliationUnifespUniv Fed Sao Paulo UNIFESP EPM, Dept Microbiol Immunol & Parasitol, Sao Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFlow Pharma, Inc.
dc.description.sponsorshipCNPq (Brazilian National Scientific Council)
dc.description.sponsorshipFAPESP (Sao Paulo State Research Foundation)
dc.description.sponsorshipIDFlow Pharma, Inc.
dc.description.sponsorshipIDCNPq
dc.description.sponsorshipIDFAPESP: 13/50302-3
dc.format.extent-
dc.identifierhttp://dx.doi.org/10.3389/fimmu.2017.00640]
dc.identifier.citationFrontiers In Immunology. Lausanne, v. 8, p. -, 2017.
dc.identifier.doi10.3389/fimmu.2017.00640
dc.identifier.fileWOS000402910200001.pdf
dc.identifier.issn1664-3224
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/53664
dc.identifier.wosWOS:000402910200001
dc.language.isoeng
dc.publisherFrontiers Media Sa
dc.relation.ispartofFrontiers In Immunology
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectZika vaccineen
dc.subjectepitopeen
dc.subjectCTL vaccineen
dc.subjectprotein foldingen
dc.subjectdengueen
dc.subjectflavivirusen
dc.subjectcomputer modelen
dc.titleAn Approach for a Synthetic CTL Vaccine Design against Zika Flavivrus Using Class I and Class II Epitopes Identified by Computer Modelingen
dc.typeinfo:eu-repo/semantics/article
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