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

Kevin R. Porter; Daniel Ewing; Lan Chen; Shuenn Jue Wu; Curtis G. Hayes; Marilyn Ferrari; Nimfa Teneza-Mora; Kanakatte Raviprakash

doi:10.1016/j.vaccine.2011.10.085

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

Kevin R. Porter^*, Daniel Ewing, Lan Chen, Shuenn Jue Wu, Curtis G. Hayes, Marilyn Ferrari, Nimfa Teneza-Mora, Kanakatte Raviprakash

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

55 Scopus citations

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.

Original language	English
Pages (from-to)	336-341
Number of pages	6
Journal	Vaccine
Volume	30
Issue number	2
DOIs	https://doi.org/10.1016/j.vaccine.2011.10.085
State	Published - 5 Jan 2012
Externally published	Yes

Keywords

DNA vaccine
Dengue
Vaxfectin

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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 {\textregistered}, a lipid-based adjuvant, enhances the immunogenicity of DNA vaccines. We conducted a nonhuman primate study to evaluate the effect of Vaxfectin {\textregistered} 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 {\textregistered}-adjuvanted tetravalent dengue DNA vaccine. The use of Vaxfectin {\textregistered} 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 {\textregistered}-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 {\textregistered}-adjuvanted tetravalent dengue DNA vaccine in a Phase 1 clinical trial.",

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AU - Hayes, Curtis G.

AU - Ferrari, Marilyn

AU - Teneza-Mora, Nimfa

AU - Raviprakash, Kanakatte

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

Abstract

Keywords

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