title: A novel tetravalent formulation combining the four aggregated domain III-capsid proteins from dengue viruses induces a functional immune response in mice and monkeys.
abstract: Our group developed a subunit vaccine candidate against dengue virus based on two different viral regions: the domain III of the envelope protein and the capsid protein. The novel chimeric protein from dengue-2 virus [domain III-capsid (DIIIC-2)], when presented as aggregated incorporating oligodeoxynucleotides, induced anti-viral and neutralizing antibodies, a cellular immune response and conferred significant protection to mice and monkeys. The remaining constructs were already obtained and properly characterized. Based on this evidence, this work was aimed at assessing the immune response in mice of the chimeric proteins DIIIC of each serotype, as monovalent and tetravalent formulations. Here, we demonstrated the immunogenicity of each protein in terms of humoral and cell-mediated immunity, without antigen competition on the mixture forming the formulation tetra DIIIC. Accordingly, significant protection was afforded as measured by the limited viral load in the mouse encephalitis model. The assessment of the tetravalent formulation in non-human primates was also conducted. In this animal model, it was demonstrated that the formulation induced neutralizing antibodies and memory cell-mediated immune response with IFN-γ-secreting and cytotoxic capacity, regardless the route of immunization used. Taken together, we can assert that the tetravalent formulation of DIIIC proteins constitutes a promising vaccine candidate against dengue virus, and propose it for further efficacy experiments in monkeys or in the dengue human infection model, as it has been recently proposed.
authors: Vaccine Division, Center for Genetic Engineering and Biotechnology, Havana 6 10 600, Cuba.
authors: Edith
authors: E
authors: Suzarte
authors: Vaccine Division, Center for Genetic Engineering and Biotechnology, Havana 6 10 600, Cuba.
authors: Lázaro
authors: L
authors: Gil
authors: Vaccine Division, Center for Genetic Engineering and Biotechnology, Havana 6 10 600, Cuba.
authors: Iris
authors: I
authors: Valdés
authors: Vaccine Division, Center for Genetic Engineering and Biotechnology, Havana 6 10 600, Cuba.
authors: Ernesto
authors: E
authors: Marcos
authors: Vaccine Division, Center for Genetic Engineering and Biotechnology, Havana 6 10 600, Cuba.
authors: Laura
authors: L
authors: Lazo
authors: Pan American Health Organization/Word Health Organization Collaborating Center for the Study of Dengue and its Vector, Department of Virology, Pedro Kourí Tropical Medicine Institute, Havana 13 11 400, Cuba.
authors: Alienys
authors: A
authors: Izquierdo
authors: Pan American Health Organization/Word Health Organization Collaborating Center for the Study of Dengue and its Vector, Department of Virology, Pedro Kourí Tropical Medicine Institute, Havana 13 11 400, Cuba.
authors: Angélica
authors: A
authors: García
authors: Vaccine Division, Center for Genetic Engineering and Biotechnology, Havana 6 10 600, Cuba.
authors: Lázaro
authors: L
authors: López
authors: Pan American Health Organization/Word Health Organization Collaborating Center for the Study of Dengue and its Vector, Department of Virology, Pedro Kourí Tropical Medicine Institute, Havana 13 11 400, Cuba.
authors: Maylin
authors: M
authors: Álvarez
authors: Vaccine Division, Center for Genetic Engineering and Biotechnology, Havana 6 10 600, Cuba.
authors: Yusleydis
authors: Y
authors: Pérez
authors: Vaccine Division, Center for Genetic Engineering and Biotechnology, Havana 6 10 600, Cuba.
authors: Jorge
authors: J
authors: Castro
authors: Vaccine Division, Center for Genetic Engineering and Biotechnology, Havana 6 10 600, Cuba.
authors: Yaremis
authors: Y
authors: Romero
authors: Pan American Health Organization/Word Health Organization Collaborating Center for the Study of Dengue and its Vector, Department of Virology, Pedro Kourí Tropical Medicine Institute, Havana 13 11 400, Cuba.
authors: María G
authors: MG
authors: Guzmán
authors: Vaccine Division, Center for Genetic Engineering and Biotechnology, Havana 6 10 600, Cuba.
authors: Gerardo
authors: G
authors: Guillén
authors: Vaccine Division, Center for Genetic Engineering and Biotechnology, Havana 6 10 600, Cuba lisset.hermida@cigb.edu.cu.
authors: Lisset
authors: L
authors: Hermida
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000096:biosynthesis; D000914:Antibodies, Viral / Q000096:biosynthesis*; D036022:Capsid Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D002522:Chlorocebus aethiops; D003715:Dengue / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D053059:Dengue Vaccines / Q000008:administration & dosage* / Q000096:biosynthesis / Q000276:immunology; D003716:Dengue Virus / Q000276:immunology*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D056724:Immunity, Humoral / Q000187:drug effects; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D022223:Vaccines, Subunit; D019562:Viral Load / Q000187:drug effects
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D036022:Capsid Proteins; D053059:Dengue Vaccines; D009838:Oligodeoxyribonucleotides; D011993:Recombinant Fusion Proteins; D022223:Vaccines, Subunit
keywords: capsid protein; dengue virus; domain III; mice; monkeys; vaccine