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

Author Cunha-Neto, Edecio Google Scholar
Rosa, Daniela S. Autor UNIFESP Google Scholar
Harris, Paul E. Google Scholar
Olson, Tim Google Scholar
Morrow, Alex Google Scholar
Ciotlos, Serban Google Scholar
Herst, Charles V. Google Scholar
Rubsamen, Reid Martin Google Scholar
Abstract 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.
Keywords Zika vaccine
epitope
CTL vaccine
protein folding
dengue
flavivirus
computer model
xmlui.dri2xhtml.METS-1.0.item-coverage Lausanne
Language English
Sponsor Flow Pharma, Inc.
CNPq (Brazilian National Scientific Council)
FAPESP (Sao Paulo State Research Foundation)
Grant number Flow Pharma, Inc.
CNPq
FAPESP: 13/50302-3
Date 2017
Published in Frontiers In Immunology. Lausanne, v. 8, p. -, 2017.
ISSN 1664-3224 (Sherpa/Romeo, impact factor)
Publisher Frontiers Media Sa
Extent -
Origin http://dx.doi.org/10.3389/fimmu.2017.00640
Access rights ACESSO ABERTO
Type Article
Web of Science ID WOS:000402910200001
URI https://repositorio.unifesp.br/handle/11600/53664

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