An IL-15 adjuvant enhances the efficacy of a combined DNA vaccine against Brucella by increasing the CD8+ cytotoxic T cell response.

We investigated whether a combined DNA vaccine delivered together with the IL-15 gene (DNA-IL-15(+)) enhanced the immune response against Brucella abortus in mice. Mice vaccinated with DNA-IL-15(+) developed a robust humoral response; Brucella-specific antibodies exhibited a dominance of immunoglobulin G2a (IgG2a) over IgG1. Splenocytes from DNA-IL-15(+)-vaccinated mice induced significantly higher levels of IFN-gamma (P<0.01) and CD8(+) T cell response (P<0.01), suggesting induction of a T-helper-1-dominated immune response. In a specific cytotoxic-T-lymphocyte activity assay, DNA-IL-15(+) immunization elicited mainly CD8(+) T cells, which mediate cytotoxicity, but also CD4(+) T cells. In vivo depletion of T cell subsets showed that the DNA-IL-15(+)-induced protection against Brucella infection is mediated predominantly by CD8(+) T cells, although CD4(+) T cells also contribute. These data indicate that plasmid-delivered IL-15 increases the efficacy of the Brucella DNA vaccine.