A new tetravalent Dengue vaccine formulation based on four chimeric envelope domain III-capsid proteins induces a functional immune response in mice and non-human primates

It is crucial in dengue a tetravalent vaccine candidate effective against the four dengue virus (DENV) serotypes, considering the lack of long lasting cross-protective immunity among infections with either serotype, and the fact that secondary heterotypic infections can led to severe forms of the disease. In this work, it was described for the first time the generation and characterization of the protein chimeric variants domain III-capsid (DIIIC) of DENV serotypes 1, 3 and 4, based on previous evidences of the ability of DIIIC-2 protein aggregated with oligodeoxynucleotide (ODN) 39M to induce a protective immunity in mice and monkeys. The recombinant proteins DIIIC-1, 3 and 4 aggregated with the ODN 39M, independently or combined with DIIIC-2 in a tetravalent formulation were evaluated in mice, demonstrating the induction of a humoral and cellular immune response able to protect against the four viral serotypes. The tetravalent DIIIC formulation was further evaluated in monkeys administered through different routes, demonstrating the induction of functional humoral and cell immune responses, results that opens the doors to clinical trials to this new tetravalent formulation against dengue. This research granted the 2015 Award of the Cuban National Academy of Sciences.