Enhanced immunogenicity and protective efficacy in mice following a Zika DNA vaccine designed by modulation of membrane-anchoring regions and its association to adjuvants.

Autor:	Teixeira FME; Laboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Tropical Medicine Institute of São Paulo, University of São Paulo Medical School, São Paulo, Brazil.; Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil., Oliveira LM; Laboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Tropical Medicine Institute of São Paulo, University of São Paulo Medical School, São Paulo, Brazil.; Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil., Branco ACCC; Laboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Tropical Medicine Institute of São Paulo, University of São Paulo Medical School, São Paulo, Brazil.; Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil., Alberca RW; Laboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Tropical Medicine Institute of São Paulo, University of São Paulo Medical School, São Paulo, Brazil., de Sousa ESA; Laboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Tropical Medicine Institute of São Paulo, University of São Paulo Medical School, São Paulo, Brazil.; Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil., Leite BHS; Department of Virology, Aggeu Magalhães Institute, Oswaldo Cruz Foundation, Recife, Brazil., Adan WCDS; Department of Virology, Aggeu Magalhães Institute, Oswaldo Cruz Foundation, Recife, Brazil., Duarte AJDS; Laboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Tropical Medicine Institute of São Paulo, University of São Paulo Medical School, São Paulo, Brazil., Lins RD; Department of Virology, Aggeu Magalhães Institute, Oswaldo Cruz Foundation, Recife, Brazil., Sato MN; Laboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Tropical Medicine Institute of São Paulo, University of São Paulo Medical School, São Paulo, Brazil., Viana IFT; Department of Virology, Aggeu Magalhães Institute, Oswaldo Cruz Foundation, Recife, Brazil.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2024 Jan 19; Vol. 15, pp. 1307546. Date of Electronic Publication: 2024 Jan 19 (Print Publication: 2024).
DOI:	10.3389/fimmu.2024.1307546
Abstrakt:	Zika virus (ZIKV) is a re-emerging pathogen with high morbidity associated to congenital infection. Despite the scientific advances since the last outbreak in the Americas, there are no approved specific treatment or vaccines. As the development of an effective prophylactic approach remains unaddressed, DNA vaccines surge as a powerful and attractive candidate due to the efficacy of sequence optimization in achieving strong immune response. In this study, we developed four DNA vaccine constructs encoding the ZIKV prM/M (pre-membrane/membrane) and E (envelope) proteins in conjunction with molecular adjuvants. The DNA vaccine candidate (called ZK_ΔSTP), where the entire membrane-anchoring regions were completely removed, was far more immunogenic compared to their counterparts. Furthermore, inclusion of the tPA-SP leader sequence led to high expression and secretion of the target vaccine antigens, therefore contributing to adequate B cell stimulation. The ZK_ΔSTP vaccine induced high cellular and humoral response in C57BL/6 adult mice, which included high neutralizing antibody titers and the generation of germinal center B cells. Administration of ZK-ΔSTP incorporating aluminum hydroxide (Alum) adjuvant led to sustained neutralizing response. In consistency with the high and long-term protective response, ZK_ΔSTP+Alum protected adult mice upon viral challenge. Collectively, the ZK_ΔSTP+Alum vaccine formulation advances the understanding of the requirements for a successful and protective vaccine against flaviviruses and is worthy of further translational studies. Competing Interests: A patent application for the devised DNA sequence covering the ZIKV vaccine antigens combined to the tPA molecular adjuvant has been filed by IV, RL, MS and FT. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Teixeira, Oliveira, Branco, Alberca, Sousa, Leite, Adan, Duarte, Lins, Sato and Viana.)
Databáze:	MEDLINE
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