title: Recombinant vesicular stomatitis virus-based dengue-2 vaccine candidate induces humoral response and protects mice against lethal infection.
abstract: Dengue is the most important arbovirus disease throughout the world and it is responsible for more than 500,000 dengue hemorrhagic cases and 22,000 deaths every year. One vaccine was recently licensed for human use in Brazil, Mexico and Philippines and although at least seven candidates have been in clinical trials the results of the most developed CYD vaccine have demonstrated immunization problems, such as uneven protection and interference between serotypes. We constructed a vaccine candidate based on vesicular stomatitis virus (VSV) expression of pre-membrane (prM) and envelope (E) proteins of dengue-2 virus (DENV-2) and tested it in mice to evaluate immunogenicity and protection against DENV-2 infection. VSV has been successfully used as vaccine vectors for several viruses to induce strong humoral and cellular immune responses. The VSV-DENV-2 recombinant was constructed by inserting the DENV-2 structural proteins into a VSV plasmid DNA for recombinant VSV-DENV-2 recovery. Infectious recombinant VSV viruses were plaque purified and prM and E expression were confirmed by immunofluorescence and radiolabeling of proteins of infected cells. Forty Balb/C mice were inoculated through subcutaneous (s.c.) route with VSV-DENV-2 vaccine in a two doses schedule 15 d apart and 29 d after first inoculation, sera were collected and the mice were challenged with 50 lethal doses (LD50) of a neurovirulent DENV-2. The VSV-DENV-2 induced anti-DENV-2 antibodies and protected animals in the challenge experiment comparable to DENV-2 immunization control group. We conclude that VSV is a promising platform to test as a DENV vaccine and perhaps against others Flaviviridae.
authors.affiliation: a Department of Internal Medicine , School of Medicine of Ribeirão Preto, University of São Paulo , Ribeirão Preto - SP , Brazil.
authors.forename: Flavio
authors.initials: F
authors.lastname: Lauretti
authors.affiliation: b Department of Pathology , Yale University School of Medicine , New Haven , CT , USA.
authors.forename: Anasuya
authors.initials: A
authors.lastname: Chattopadhyay
authors.affiliation: a Department of Internal Medicine , School of Medicine of Ribeirão Preto, University of São Paulo , Ribeirão Preto - SP , Brazil.
authors.forename: Rafael Freitas
authors.initials: RF
authors.lastname: de Oliveira França
authors.affiliation: a Department of Internal Medicine , School of Medicine of Ribeirão Preto, University of São Paulo , Ribeirão Preto - SP , Brazil.
authors.forename: Luiza
authors.initials: L
authors.lastname: Castro-Jorge
authors.affiliation: b Department of Pathology , Yale University School of Medicine , New Haven , CT , USA.
authors.forename: John
authors.initials: J
authors.lastname: Rose
authors.affiliation: a Department of Internal Medicine , School of Medicine of Ribeirão Preto, University of São Paulo , Ribeirão Preto - SP , Brazil.
authors.forename: Benedito A L da
authors.initials: BA
authors.lastname: Fonseca
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D003715:Dengue / Q000517:prevention & control*; D053059:Dengue Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D003716:Dengue Virus / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D004337:Drug Carriers; D005822:Genetic Vectors; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008807:Mice, Inbred BALB C; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D018116:Vesiculovirus / Q000235:genetics*; D015678:Viral Structural Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D053059:Dengue Vaccines; D004337:Drug Carriers; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; D015678:Viral Structural Proteins
keywords: dengue 2; dengue vaccine candidate; mouse challenge; neutralizing antibodies; recombinant vesicular stomatitis virus