Design and production of dengue virus chimeric proteins useful for developing tetravalent vaccines

dc.creatorBatista, Izabella Cristina Andrade
dc.creatorQuinan, Bárbara Resende
dc.creatorAlves, Érica Alessandra Rocha
dc.creatorJangola, Soraya Torres Gaze
dc.creatorOliveira, Eneida Santos
dc.creatorColombarolli, Stella Garcia
dc.creatorFerreira, Jorge Gomes Goulart
dc.creatorRocha, Eliseu Soares de Oliveira
dc.creatorKroon, Erna Geessien
dc.creatorAssis, Rafael Ramiro de
dc.creatorOliveira, Jaquelline Germano de
dc.creatorFiuza, Jacqueline Araújo
dc.creatorSilva, Carlos Eduardo Calzavara
dc.date2023-05-17T14:23:15Z
dc.date2023-05-17T14:23:15Z
dc.date2020
dc.date.accessioned2023-09-26T23:50:29Z
dc.date.available2023-09-26T23:50:29Z
dc.identifierBATISTA, Izabella Cristina Andrade et al.Design and production of dengue virus chimeric proteins useful for developing tetravalent vacines. Vaccine, v. 38, n. 8, p. 2005-2015, 2020.
dc.identifier0264-410X
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/58459
dc.identifier10.1016/j.vaccine.2020.01.003
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8894792
dc.descriptionDengue virus (DENV) is a Flavivirus estimated to cause 390 million infections/year. Currently, there is no anti-viral specific treatment for dengue, and efficient DENV vector control is still unfeasible. Here, we designed and produced chimeric proteins containing potential immunogenic epitopes from the four DENV serotypes in an attempt to further compose safer, balanced tetravalent dengue vaccines. For this, South American DENV isolate sequences were downloaded from the NCBI/Virus Variation/ Dengue virus databases and intraserotype-aligned to generate four consensuses. Four homologous DENV sequences were retrieved using BLAST and then interserotype-aligned. In parallel, sequences were subjected to linear B epitope prediction analysis. Regions of the envelope and NS1 proteins that are highly homologous among the four DENV serotypes, non-conserved antigenic regions and the most antigenic epitopes found in the C, prM, E and NS1 DENV proteins were used to construct 11 chimeric peptides. Genes encoding the chimeric proteins were commercially synthesized, and proteins were expressed, purified by affinity chromatography and further subjected to ELISA assays using sera from individuals infected with DENVs 1, 2, 3 or 4. As a proof-of-concept, the chimeric EnvEpII protein was selected to immunize BALB/c and C57BL/6 mice strains. The immunization with EnvEpII protein associated with aluminum induced an increased number of T CD4(+) and CD8(+) cells, high production of IgG(1) and IgG(2) antibodies, and increased levels of IL-2 and IL-17 cytokines, in both mouse strains. Because the EnvEpII protein associated with aluminum induced an efficient cellular response by stimulating the production of IL-2, IL-4, IL-17 and induced a robust humoral response in mice, we conclude that it resembles an efficient specific response against DENV infection. Although further experiments are required, our results indicate that epitope selection by bioinformatic tools is efficient to create recombinant proteins that can be used as candidates for the development of vaccines against infectious diseases.
dc.description2099-12-31
dc.formatapplication/pdf
dc.languageeng
dc.publisherElsevier
dc.rightsrestricted access
dc.subjectDengue
dc.subjectTetravalent vaccin
dc.subjectChimeric proteins
dc.titleDesign and production of dengue virus chimeric proteins useful for developing tetravalent vaccines
dc.typeArticle


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