A tetravalent dengue vaccine containing a mix of domain III-P64k and domain III-capsid proteins induces a protective response in mice.

Recombinant fusion proteins containing domain III of the dengue virus envelope protein fused to the P64k protein from Neisseria meningitidis and domain III of dengue virus type 2 (D2) fused to the capsid protein of this serotype were immunogenic and conferred protection in mice against lethal challenge, as reported previously. Combining the domain III-P64k recombinant proteins of dengue virus types 1, 3 and 4 (D1, D3, and D4) with the domain III-capsid protein from D2, we obtained a novel tetravalent formulation containing different antigens. Here, the IgG and neutralizing antibody response, the cellular immune response, and the protective capacity against lethal challenge in mice immunized with this tetravalent formulation were evaluated. The neutralizing antibody response obtained against D1, D2 and D3, together with the high levels of IFNγ secretion induced after stimulation with the four dengue serotypes, supports the strategy of using a new tetravalent formulation containing domain III of the envelope protein fused to the capsid protein of each dengue virus serotype.