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

• DOI: 10.1016/j.vaccine.2011.10.085
• Publication Date: 2011-11-14T07:35:14Z
• Authors: Kevin R. Porter; Daniel Ewing; Lan Chen; Shuenn-Jue Wu; Curtis G. Hayes; Marilyn Ferrari; Nimfa Teneza-Mora; Kanakatte Ravipra...
• Keywords: Primates; 0301 basic medicine; Enzyme-Linked Immunospot Assay; Phosphatidylethanolamines; T-Lymphocytes; Primate Diseases; Dengue Vaccines; Antibodies, Viral; Antibodies, Neutralizing; Macaca mulatta; 3. Good health; Dengue; Disease Models, Animal; 03 medical and health sciences; Adjuvants, Immunologic; Vaccines, DNA; Animals; Viremia

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 3mg 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.