A West Nile Virus DNA Vaccine Utilizing a Modified Promoter Induces Neutralizing Antibody in Younger and Older Healthy Adults in a Phase I Clinical Trial

Publication Type
Journal Article
Year of Publication
2011
Authors
Ledgerwood, JE; Pierson, TC; Hubka, SA; Desai, N; Rucker, S; Gordon, IJ; Enama, ME; Nelson, S; Nason, M; Gu, W; Bundrant, N; Koup, RA; Bailer, RT; Mascola, JR; Nabel, GJ; Graham, BS; The VRC 303 Study Team
Secondary
J Infect Dis
Volume
203
Start Page
1396
Pagination
1396-1404
Date Published
05/2011
Keywords
Antibodies; DNA/immunology; Neutralizing/blood/immunology Antibodies; T-Lymphocytes/immunology; Vaccines; Viral Vaccines; Viral/blood; West Nile Fever/prevention & control
ISBN
0022-1899
Abstract

BACKGROUND:

West Nile virus (WNV) is a flavivirus that causes meningitis and encephalitis. There are no licensed vaccines to prevent WNV in humans. The safety and immunogenicity of a first-generation WNV DNA vaccine was demonstrated in a clinical trial and a similar DNA vaccine has been licensed for use in horses.

METHODS:

A DNA vaccine encoding the protein premembrane and the E glycoproteins of the NY99 strain of WNV under the transcriptional control of the CMV/R promoter was evaluated in an open-label study in 30 healthy adults. Half of the subjects were age 18-50 years and half were age 51-65 years. Immune responses were assessed by enzyme-linked immunosorbent assay, neutralization assays, intracellular cytokine staining, and ELISpot.

RESULTS:

The 3-dose vaccine regimen was safe and well tolerated. Vaccine-induced T cell and neutralizing antibody responses were detected in the majority of subjects. The antibody responses seen in the older age group were of similar frequency, magnitude, and duration as those seen in the younger cohort.

CONCLUSIONS:

Neutralizing antibody responses to WNV were elicited by DNA vaccination in humans, including in older individuals, where responses to traditional vaccine approaches are often diminished. This DNA vaccine elicited T cell responses of greater magnitude when compared with an earlier-generation construct utilizing a CMV promoter.