A vaccine formulation consisting of nucleocapsid-like particles from Dengue-2 and the fusion protein P64k-domain III from Dengue-1 induces a protective immune response against the homologous serotypes in mice

摘要

In previous studies we reported the cloning, expression and purification of the capsid protein from Dengue-2 virus. Subsequently, we described an in vitro-assembly process for the capsid protein, which resulted in nucleocapsid-like particles (recNLPs) that induced functional cell-mediated immunity and protection in mice. Moreover, our group reported the evaluation in non-human primates of the fusion protein P64k-domain III from Dengue-1 (PD10). This protein proved to be immunogenic and protective when Freund's adjuvant, but not alum, was used. Based on the previously demonstrated capacity of recNLPs to potentiate the immunogenicity of heterologous proteins, in this study we assess the immune response elicited by the formulation PD10-recNLPs-alum and its protective capacity against Dengue-1 and Dengue-2 virus. As expected, the humoral immune response was mainly directed against Dengue-1, while high levels of IFN-γ secretion were detected after stimulation with Dengue-1 and Dengue-2. Consistently, animals immunized with the bivalent formulation were significantly protected against challenge with either Dengue serotype. In conclusion, this report describes a novel formulation based on recombinant proteins and alum, which is protective against Dengue-1 and Dengue-2 in mice.