A dose-response study in mice of a tetravalent vaccine candidate composed of domain III-capsid proteins from dengue viruses

• Published in: Archives of virology Vol. 162; no. 8; pp. 2247 - 2256
• Main Authors: Valdés, Iris, Marcos, Ernesto, Suzarte, Edith, Pérez, Yusleidi, Brown, Enma, Lazo, Laura, Cobas, Karem, Yaugel, Melyssa, Rodríguez, Yadira, Gil, Lázaro, Guillén, Gerardo, Hermida, Lisset
• Format: Journal Article
• Language: English
• Published: Vienna Springer Vienna 01.08.2017; Springer Nature B.V
• Subjects: Animals; Antibodies, Neutralizing - blood; Antibodies, Viral - blood; Biomedical and Life Sciences; Biomedicine; Brain - virology; Capsid protein; Capsid Proteins - genetics; Capsid Proteins - immunology; Cell-mediated immunity; Cercopithecus aethiops; Dengue - prevention & control; Dengue fever; Dengue Vaccines - immunology; Dengue Virus; Disease Models, Animal; Dose-Response Relationship, Immunologic; Encephalitis; Female; Immune response (humoral); Immunity, Cellular; Immunity, Humoral; Immunogenicity; Immunostimulation; Infectious Diseases; Medical Microbiology; Mice; Mice, Inbred BALB C; Oligonucleotides; Original Article; Proteins; Recombinant Proteins - immunology; Serotypes; Vaccines; Vaccines, Subunit - immunology; Vero Cells; Viral envelope proteins; Viremia; Virology; Viruses; Dengue Hemorrhagic Fever; Cellular Immune Response; Vaccine Candidate; DENV Infection; Dengue Virus
• ISSN: 0304-8608; 1432-8798
• DOI: 10.1007/s00705-017-3360-y

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.