title: A dose-response study in mice of a tetravalent vaccine candidate composed of domain III-capsid proteins from dengue viruses.
abstract: Tetra DIIIC is a subunit vaccine candidate based on domain III of the envelope protein and the capsid protein of the four serotypes of dengue virus. This vaccine preparation contains the DIIIC proteins aggregated with a specific immunostimulatory oligodeoxynucleotide (ODN 39M). Tetra DIIIC has already been shown to be immunogenic and protective in mice and monkeys. In this study, we evaluated the immunogenicity in mice of several formulations of Tetra DIIIC containing different amounts of the recombinant proteins. The Tetra DIIIC formulation induced a humoral immune response against the four DENV serotypes, even at the lowest dose assayed. In contrast, the highest level of cell-mediated immunity, measured as frequency of IFNγ-producing cells, was detected in animals immunized with the lowest dose. The protective capacity of the tetravalent formulations was assessed using the mouse model of dengue virus encephalitis. Upon challenge, vaccinated mice showed significantly reduced virus replication in all tested groups. This study provides new information about the functionality of Tetra DIIIC as a vaccine candidate and also supports the crucial role of cell-mediated immunity in protection against dengue virus.
authors.affiliation: Vaccine Division, Center for Genetic Engineering and Biotechnology (CIGB), Avenue 31, P.O. Box 6162, 10 600, Havana 6, Cuba.
authors.forename: Iris
authors.initials: I
authors.lastname: Valdés
authors.affiliation: Vaccine Division, Center for Genetic Engineering and Biotechnology (CIGB), Avenue 31, P.O. Box 6162, 10 600, Havana 6, Cuba.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Marcos
authors.affiliation: Vaccine Division, Center for Genetic Engineering and Biotechnology (CIGB), Avenue 31, P.O. Box 6162, 10 600, Havana 6, Cuba.
authors.forename: Edith
authors.initials: E
authors.lastname: Suzarte
authors.affiliation: Vaccine Division, Center for Genetic Engineering and Biotechnology (CIGB), Avenue 31, P.O. Box 6162, 10 600, Havana 6, Cuba.
authors.forename: Yusleidi
authors.initials: Y
authors.lastname: Pérez
authors.affiliation: Vaccine Division, Center for Genetic Engineering and Biotechnology (CIGB), Avenue 31, P.O. Box 6162, 10 600, Havana 6, Cuba.
authors.forename: Enma
authors.initials: E
authors.lastname: Brown
authors.affiliation: Vaccine Division, Center for Genetic Engineering and Biotechnology (CIGB), Avenue 31, P.O. Box 6162, 10 600, Havana 6, Cuba.
authors.forename: Laura
authors.initials: L
authors.lastname: Lazo
authors.affiliation: Vaccine Division, Center for Genetic Engineering and Biotechnology (CIGB), Avenue 31, P.O. Box 6162, 10 600, Havana 6, Cuba.
authors.forename: Karem
authors.initials: K
authors.lastname: Cobas
authors.affiliation: Vaccine Division, Center for Genetic Engineering and Biotechnology (CIGB), Avenue 31, P.O. Box 6162, 10 600, Havana 6, Cuba.
authors.forename: Melyssa
authors.initials: M
authors.lastname: Yaugel
authors.affiliation: Vaccine Division, Center for Genetic Engineering and Biotechnology (CIGB), Avenue 31, P.O. Box 6162, 10 600, Havana 6, Cuba.
authors.forename: Yadira
authors.initials: Y
authors.lastname: Rodríguez
authors.affiliation: Vaccine Division, Center for Genetic Engineering and Biotechnology (CIGB), Avenue 31, P.O. Box 6162, 10 600, Havana 6, Cuba. lazaro.gil@cigb.edu.cu.
authors.forename: Lázaro
authors.initials: L
authors.lastname: Gil
authors.affiliation: Vaccine Division, Center for Genetic Engineering and Biotechnology (CIGB), Avenue 31, P.O. Box 6162, 10 600, Havana 6, Cuba.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Guillén
authors.affiliation: Vaccine Division, Center for Genetic Engineering and Biotechnology (CIGB), Avenue 31, P.O. Box 6162, 10 600, Havana 6, Cuba. lisset.hermida@cigb.edu.cu.
authors.forename: Lisset
authors.initials: L
authors.lastname: Hermida
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood*; D001921:Brain / Q000821:virology; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology*; D002522:Chlorocebus aethiops; D003715:Dengue / Q000517:prevention & control*; D053059:Dengue Vaccines / Q000276:immunology*; D003716:Dengue Virus; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000276:immunology; D022223:Vaccines, Subunit / Q000276:immunology; D014709:Vero Cells; D014766:Viremia
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D036022:Capsid Proteins; D053059:Dengue Vaccines; D011994:Recombinant Proteins; D022223:Vaccines, Subunit