Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSPTEIXEIRA, Franciane Mouradian EmidioOLIVEIRA, Luana de MendoncaBRANCO, Anna Claudia Calvielli CasteloALBERCA, Ricardo WesleySOUSA, Emanuella Sarmento Alho deLEITE, Bruno Henrique de SousaADAN, Wenny Camilla dos SantosDUARTE, Alberto Jose da SilvaLINS, Roberto DiasSATO, Maria NotomiVIANA, Isabelle Freire Tabosa2024-04-052024-04-052024FRONTIERS IN IMMUNOLOGY, v.15, article ID 1307546, 12p, 20241664-3224https://observatorio.fm.usp.br/handle/OPI/59033Zika 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_Delta STP), 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_Delta STP 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-Delta STP incorporating aluminum hydroxide (Alum) adjuvant led to sustained neutralizing response. In consistency with the high and long-term protective response, ZK_Delta STP+Alum protected adult mice upon viral challenge. Collectively, the ZK_Delta STP+Alum vaccine formulation advances the understanding of the requirements for a successful and protective vaccine against flaviviruses and is worthy of further translational studies.engopenAccessDNA vaccineZika virusenvelope proteinmembrane-anchoring regionsadjuvantsprotectionimmunogenicityclass-ii compartmentimmune-responsessignal sequencesvirus challengens1 geneproteindengueimmunizationantibodiesincreasesarticleCopyright FRONTIERS MEDIA SA10.3389/fimmu.2024.1307546Immunology