8th Cuban Congress on Microbiology and Parasitology, 5th National Congress on Tropical Medicine and 5th International Symposium on HIV/aids infection in Cuba

Title

TETRA DIIIC: A NOVEL VACCINE CANDIDATE AGAINST DENGUE

Authors

Lisset Hermida Cruz , Lázaro Gil González , Ernesto Marcos López , Alienys Izquierdo Oliva , Edith Suzarte . , Iris Valdés Prado , Laura Lazo Vázquez , Mayling Álvarez Vera , Yusleydis de la C. Pérez Fuentes , Jorge Castro . , Yaremis Romero . , María Guadalupe Guzmán Tirado , Gerardo Guillén .

Abstract


Introduction: It is estimated that nearly half of the world’s population is at risk of infection with dengue virus, with up to 50 million people infected each year and frequent epidemic activity in Southeast Asia, South America and Western Pacific regions. Our group has developed a subunit vaccine candidate against dengue based on two different viral regions: the domain III of the envelope (E) protein and the capsid protein. In the present work, a summary of results obtained with this vaccine candidate, is presented. Materials and methods: Mice and monkeys experiments were carried out to characterize the immune response generated with the monovalent and tetravalent formulations containing the four recombinant proteins DIIICs. The main markers tested were neutralizing antibodies, cell-mediated immunity and protection against viral challenge in the two animal models. Results: The novel chimeric protein from dengue-2 virus (domain III-capsid (DIIIC-2)), when presented as particulate aggregated incorporating oligodeoxynucleotides, induced antiviral and neutralizing antibodies, cellular immune response, and conferred significant protection to mice and monkeys. Furthermore, the rest of constructs were obtained and proper characterized. In the mice experiment it was demonstrated the immunogenicity of each protein in terms of humoral and cell-mediated immunity. In addition, significant protection was afforded as measured by the limited viral load in the immunized animals. Finally, upon monkey immunization with the tetravalent formulation, it was demonstrated that 100% of the animals were positive by neutralizing antibodies and CMI, regardless the route of immunization used. Conclusions: Taken together we can assert that tetra DIIIC constitutes a promising vaccine candidate against the four dengue serotypes, and propose it for the further efficacy experiments in NHP against the four dengue serotypes.