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: Kevin R Porter, Daniel Ewing, Lan Chen, Shuenn-Jue Wu, Curtis G Hayes, Marilyn Ferrari, Nimfa Teneza-Mora, Kanakatte Raviprakash
• Journal: Vaccine (Vaccine) Vol. 30 Issue 2 Pg. 336-41 (Jan 05 2012) ISSN: 1873-2518 [Electronic] Netherlands
• PMID: 22085548 (Publication Type: Journal Article)
• Copyright: Published by Elsevier Ltd.

Chemical References

• Adjuvants, Immunologic
• Antibodies, Neutralizing
• Antibodies, Viral
• Dengue Vaccines
• Phosphatidylethanolamines
• Vaccines, DNA
• vaxfectin

Topics

• Adjuvants, Immunologic (administration & dosage)
• Animals
• Antibodies, Neutralizing (blood)
• Antibodies, Viral (blood)
• Dengue (prevention & control, veterinary)
• Dengue Vaccines (administration & dosage, immunology)
• Disease Models, Animal
• Enzyme-Linked Immunospot Assay
• Macaca mulatta
• Phosphatidylethanolamines (administration & dosage)
• Primate Diseases (prevention & control)
• Primates
• T-Lymphocytes (immunology)
• Vaccines, DNA (administration & dosage, immunology)
• Viremia (prevention & control)