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

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorTEIXEIRA, Franciane Mouradian Emidio
dc.contributor.authorOLIVEIRA, Luana de Mendonca
dc.contributor.authorBRANCO, Anna Claudia Calvielli Castelo
dc.contributor.authorALBERCA, Ricardo Wesley
dc.contributor.authorSOUSA, Emanuella Sarmento Alho de
dc.contributor.authorLEITE, Bruno Henrique de Sousa
dc.contributor.authorADAN, Wenny Camilla dos Santos
dc.contributor.authorDUARTE, Alberto Jose da Silva
dc.contributor.authorLINS, Roberto Dias
dc.contributor.authorSATO, Maria Notomi
dc.contributor.authorVIANA, Isabelle Freire Tabosa
dc.date.accessioned2024-04-05T19:35:42Z
dc.date.available2024-04-05T19:35:42Z
dc.date.issued2024
dc.description.abstractZika 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.eng
dc.description.indexMEDLINE
dc.description.indexPubMed
dc.description.indexScopus
dc.description.indexDimensions
dc.description.indexWoS
dc.description.sponsorshipLaboratorio de Investigacao Medica, Unidade 56, Department of Dermatology, School of Medicine, University of Sao Paulo, Brazil
dc.description.sponsorshipFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2018/18230-6, 2019/25119-7]
dc.description.sponsorshipState of Pernambuco Funding Agency (Fundacaao de Amparo a Ciencia e Tecnologia do Estado de Pernambuco - FACEPE) [BFP-0010-2.11/22, APQ-0346-2.09/19]
dc.description.sponsorshipNational Council for Scientific and Technological Development (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico - CNPq) [165071/2018-4, 303833/2022-0, 425997/2018-9]
dc.description.sponsorshipOswaldo Cruz Foundation through the Innovation Program (INOVA) [VPPCB-007-FIO-18-2-134, IAM-005-FIO-22-2-44]
dc.description.sponsorshipEuropean Union [H2020 734548]
dc.description.sponsorshipCuraZika Foundation [0061012]
dc.identifier.citationFRONTIERS IN IMMUNOLOGY, v.15, article ID 1307546, 12p, 2024
dc.identifier.doi10.3389/fimmu.2024.1307546
dc.identifier.issn1664-3224
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/59033
dc.language.isoeng
dc.publisherFRONTIERS MEDIA SAeng
dc.relation.ispartofFrontiers in Immunology
dc.rightsopenAccesseng
dc.rights.holderCopyright FRONTIERS MEDIA SAeng
dc.subjectDNA vaccineeng
dc.subjectZika viruseng
dc.subjectenvelope proteineng
dc.subjectmembrane-anchoring regionseng
dc.subjectadjuvantseng
dc.subjectprotectioneng
dc.subjectimmunogenicityeng
dc.subject.otherclass-ii compartmenteng
dc.subject.otherimmune-responseseng
dc.subject.othersignal sequenceseng
dc.subject.othervirus challengeeng
dc.subject.otherns1 geneeng
dc.subject.otherproteineng
dc.subject.otherdengueeng
dc.subject.otherimmunizationeng
dc.subject.otherantibodieseng
dc.subject.otherincreaseseng
dc.subject.wosImmunologyeng
dc.titleEnhanced immunogenicity and protective efficacy in mice following a Zika DNA vaccine designed by modulation of membrane-anchoring regions and its association to adjuvantseng
dc.typearticleeng
dc.type.categoryoriginal articleeng
dc.type.versionpublishedVersioneng
dspace.entity.typePublication
hcfmusp.author.externalLEITE, Bruno Henrique de Sousa:Fundacao Oswaldo Cruz, Aggeu Magalhaes Inst, Dept Virol, Recife, Brazil
hcfmusp.author.externalADAN, Wenny Camilla dos Santos:Fundacao Oswaldo Cruz, Aggeu Magalhaes Inst, Dept Virol, Recife, Brazil
hcfmusp.author.externalLINS, Roberto Dias:Fundacao Oswaldo Cruz, Aggeu Magalhaes Inst, Dept Virol, Recife, Brazil
hcfmusp.author.externalVIANA, Isabelle Freire Tabosa:Fundacao Oswaldo Cruz, Aggeu Magalhaes Inst, Dept Virol, Recife, Brazil
hcfmusp.citation.scopus0
hcfmusp.contributor.author-fmusphcFRANCIANE MOURADIAN EMIDIO TEIXEIRA
hcfmusp.contributor.author-fmusphcLUANA DE MENDONCA OLIVEIRA
hcfmusp.contributor.author-fmusphcANNA CLAUDIA CALVIELLI CASTELLO BRANCO
hcfmusp.contributor.author-fmusphcRICARDO WESLEY ALBERCA CUSTODIO
hcfmusp.contributor.author-fmusphcEMANUELLA SARMENTO ALHO DE SOUSA
hcfmusp.contributor.author-fmusphcALBERTO JOSE DA SILVA DUARTE
hcfmusp.contributor.author-fmusphcMARIA NOTOMI SATO
hcfmusp.description.articlenumber1307546
hcfmusp.description.volume15
hcfmusp.origemWOS
hcfmusp.origem.dimensionspub.1168055071
hcfmusp.origem.pubmed38361945
hcfmusp.origem.scopus2-s2.0-85185111645
hcfmusp.origem.wosWOS:001161460700001
hcfmusp.publisher.cityLAUSANNEeng
hcfmusp.publisher.countrySWITZERLANDeng
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