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Polymer brushes as a delivery tool to increase the immunogenicity of a Zika Virus DNA vaccine model

Grant number: 21/12476-6
Support type:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): June 14, 2022
Effective date (End): June 13, 2023
Field of knowledge:Biological Sciences - Immunology
Principal researcher:Maria Notomi Sato
Grantee:Franciane Mouradian Emidio Teixeira
Supervisor abroad: Julien Gautrot
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Research place: Queen Mary University of London, England  
Associated to the scholarship:18/18230-6 - Evaluation of the efficacy of the Zika Virus chimeric DNA vaccine and the lysosomal-associated membrane protein in mice, BP.DR

Abstract

DNA vaccines are safety and stable gene expression vectors, with easy design of genetic sequences, which allows molecular manipulation to ensure improved immunogenicity. However, naked plasmids present limitations that can compromise their effectiveness. We previously developed an optimized DNA vaccine to Zika virus (ZIKV) consisting of the DNA sequence coding for the viral antigens carried by the pcDNA3.1 expression plasmid. This strategy elicited strong humoral response that prevented adult mice infection, but the antibody titer has decreased after 2 months post immunization. We hypothesize that the naked DNA only has promoted limited expression of the antigens in situ. Here we propose to optimize our ZIKV DNA vaccine delivery system aiming more effective cellular delivery in order to promote a sustained antigen expression and to lead to an improved long-term immunogenicity. In this proposal, we will develop a gene delivery vector design based on the use of polymer brush-functionalised nanoparticles, which will allow the evaluation of the vaccine antigen's cellular distribution and location at short to long time points. This project proposes to introduce for the first time the use of polymer brush-based nanomaterials for DNA vaccine design and will evaluate the suitability of this strategy as ZIKV vaccine candidate. Prof. Gautrot's laboratory has pioneered the use of polymer brush-based nanomaterials to deliver DNA or RNA molecules. We believe this innovative technology will providing a promising approach to tackle not only the ZIKV problem, but also other pathogens of public health importance.

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