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

Autor:	Cunha-Neto E; Laboratory of Clinical Immunology and Allergy-LIM60, University of São Paulo School of Medicine, São Paulo, Brazil.; Institute for Investigation in Immunology (III) INCT, São Paulo, Brazil.; School of Medicine, Heart Institute (Incor), University of São Paulo, São Paulo, Brazil., Rosa DS; Institute for Investigation in Immunology (III) INCT, São Paulo, Brazil.; Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo (UNIFESP/EPM), São Paulo, Brazil., Harris PE; Endocrinology Division, Department of Medicine, School of Medicine, Columbia University, New York, NY, United States., Olson T; Flow Pharma, Inc., Redwood City, CA, United States., Morrow A; Flow Pharma, Inc., Redwood City, CA, United States., Ciotlos S; Flow Pharma, Inc., Redwood City, CA, United States., Herst CV; Flow Pharma, Inc., Redwood City, CA, United States., Rubsamen RM; Flow Pharma, Inc., Redwood City, CA, United States.; Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2017 Jun 09; Vol. 8, pp. 640. Date of Electronic Publication: 2017 Jun 09 (Print Publication: 2017).
DOI:	10.3389/fimmu.2017.00640
Abstrakt:	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.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu