title: Immunogenicity and protective efficacy of a vaxfectin-adjuvanted tetravalent dengue DNA vaccine.
abstract: 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.
authors.affiliation: Viral and Rickettsial Diseases Department, Naval Medical Research Center, Silver Spring, MD, USA. kevin.porter@med.navy.mil
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Porter
authors.forename: Daniel
authors.initials: D
authors.lastname: Ewing
authors.forename: Lan
authors.initials: L
authors.lastname: Chen
authors.forename: Shuenn-Jue
authors.initials: SJ
authors.lastname: Wu
authors.forename: Curtis G
authors.initials: CG
authors.lastname: Hayes
authors.forename: Marilyn
authors.initials: M
authors.lastname: Ferrari
authors.forename: Nimfa
authors.initials: N
authors.lastname: Teneza-Mora
authors.forename: Kanakatte
authors.initials: K
authors.lastname: Raviprakash
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D003715:Dengue / Q000517:prevention & control / Q000662:veterinary*; D053059:Dengue Vaccines / Q000008:administration & dosage / Q000276:immunology*; D004195:Disease Models, Animal; D058501:Enzyme-Linked Immunospot Assay; D008253:Macaca mulatta; D010714:Phosphatidylethanolamines / Q000008:administration & dosage*; D018419:Primate Diseases / Q000517:prevention & control*; D011323:Primates; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D014766:Viremia / Q000517:prevention & control
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D053059:Dengue Vaccines; D010714:Phosphatidylethanolamines; D019444:Vaccines, DNA; C460866:vaxfectin