A DNA vaccine candidate expressing dengue-3 virus prM and E proteins elicits neutralizing antibodies and protects mice against lethal challenge

Autor(es)

De Paula, Sergio Oliveira ^{[1, 2]} ; Lima, Danielle Malta ^{[3, 4]} ; de Oliveira Franca, Rafael Freitas ^[3] ; Gomes-Ruiz, Alessandra Cristina ^{[3, 4]} ; Lopes da Fonseca, Benedito Antonio ^[3]

Afiliação do(s) autor(es)

^[1] Univ Fed Vi, Dept Biol Geral, LaboratA, Rio Imunovirologia Mol, BR-36570000 CEP 36570000 - Brazil

^[2] Univ Fed Vicosa, Dept Biol Geral, Lab Imunovirol Mol, BR-36570000 Vicosa, MG - Brazil

^[3] Univ Sao Paulo, Sch Med Ribeirao, Dept Internal Med, Ribeirao Preto - Brazil

^[4] Preto, Univ SA, Sch Med Ribeirao, Dept Internal Med, Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: ARCHIVES OF VIROLOGY; v. 153, n. 12, p. 2215-2223, DEC 2008.
• Citações Web of Science: 20

Resumo

In an effort to develop a suitable DNA vaccine candidate for dengue, using dengue-3 virus (DENV-3) as a prototype, the genes coding for premembrane (prM) and envelope proteins (E) were inserted into an expression plasmid. After selecting recombinant clones containing prM/E genes, protein expression in the cell monolayer was detected by indirect immunofluorescence and immunoprecipitation assays. After selecting three vaccine candidates (pVAC1DEN3, pVAC2DEN3 and pVAC3DEN3), they were analyzed in vivo to determine their ability to induce a DENV-3-specific immune response. After three immunizations, the spleens of the immunized animals were isolated, and the cells were cultivated to measure cytokine levels by ELISA and used for lymphoproliferation assays. All of the animals inoculated with the recombinant clones induced neutralizing antibodies against DENV-3 and produced a T cell proliferation response after specific stimuli. Immunized and control mice were challenged with a lethal dose of DENV-3 and observed in order to assess their survival capability. The groups that presented the best survival rate after the challenge were the animals vaccinated with the pVAC3DEN3 clones, with an 80% survival rate. Thus, these data show that we have manufactured a vaccine candidate for DENV-3 that is able to induce a specific immune response and protects mice against a lethal challenge. (AU)

• Processo FAPESP: 00/09287-0 - Produção de vacina de DNA recombinante para o vírus dengue-3
• Beneficiário: Sérgio Oliveira de Paula
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 00/12957-8 - Producao de vacina de dna recombinante para o virus dengue-3.
• Beneficiário: Benedito Antônio Lopes da Fonseca
• Modalidade de apoio: Auxílio à Pesquisa - Regular