Immunogenicity and protective efficacy of a vaxfectin-adjuvanted tetravalent dengue DNA vaccine

A prototype dengue-1 DNA vaccine was shown to be safe and immunogenic in a previous Phase 1 clinical trial. Anti-dengue-1 neutralizing antibody responses were detectable only in the group of volunteers receiving the high dose of nonadjuvanted vaccine and the antibody titers were low. Vaxfectin®, a lipid-based adjuvant, enhances the immunogenicity of DNA vaccines. We conducted a nonhuman primate study to evaluate the effect of Vaxfectin® on the immunogenicity of a tetravalent dengue DNA vaccine. Animals were immunized on days 0, 28 and 84, with each immunization consisting of 3 mg of Vaxfectin®-adjuvanted tetravalent dengue DNA vaccine. The use of Vaxfectin® resulted in a significant increase in anti-dengue neutralizing antibody responses against dengue-1, -3 and -4. There was little to no effect on T cell responses as measured by interferon gamma ELISPOT assay. Animals immunized with the Vaxfectin®-formulated tetravalent DNA vaccine showed significant protection against live dengue-2 virus challenge compared to control animals (0.75 mean days of viremia vs 3.3 days). Animals vaccinated with nonadjuvanted DNA had a mean 2.0 days of viremia. These results support further evaluation of the Vaxfectin®-adjuvanted tetravalent dengue DNA vaccine in a Phase 1 clinical trial.

► A nonhuman primate study evaluated an adjuvanted tetravalent dengue DNA vaccine.
► The adjuvant Vaxfectin® significantly improved neutralizing antibody responses.
► Protection against challenge was significantly enhanced with the adjuvanted vaccine.
► The Vaxfectin® adjuvant did not enhance anti-dengue cellular immune responses.