A West Nile virus DNA vaccine induces neutralizing antibody in healthy adults during a phase 1 clinical trial

J Infect Dis. 2007 Dec 15;196(12):1732-40. doi: 10.1086/523650.

Abstract

Background: West Nile virus (WNV) is a mosquito-borne flavivirus that can cause severe meningitis and encephalitis in infected individuals. We report the safety and immunogenicity of a WNV DNA vaccine in its first phase 1 human study.

Methods: A single-plasmid DNA vaccine encoding the premembrane and the envelope glycoproteins of the NY99 strain of WNV was evaluated in an open-label study in 15 healthy adults. Twelve subjects completed the 3-dose vaccination schedule, and all subjects completed 32 weeks of evaluation for safety and immunogenicity. The development of a vaccine-induced immune response was assessed by enzyme-linked immunosorbant assay, neutralization assays, intracelluar cytokine staining, and enzyme-linked immunospot assay.

Results: The vaccine was safe and well tolerated, with no significant adverse events. Vaccine-induced T cell and antibody responses were detected in the majority of subjects. Neutralizing antibody to WNV was detected in all subjects who completed the 3-dose vaccination schedule, at levels shown to be protective in studies of horses, an incidental natural host for WNV.

Conclusions: Further assessment of this DNA platform for human immunization against WNV is warranted.

Trial registration: ClinicalTrials.gov identifier: NCT00106769 .

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Viral / biosynthesis*
  • Antibodies, Viral / immunology
  • Enzyme-Linked Immunosorbent Assay / methods
  • Female
  • Humans
  • Male
  • Middle Aged
  • T-Lymphocytes / immunology
  • Vaccines, DNA / genetics
  • Vaccines, DNA / immunology
  • Vaccines, DNA / therapeutic use*
  • Vaccines, DNA / virology
  • West Nile Fever / prevention & control*
  • West Nile Fever / virology
  • West Nile Virus Vaccines / genetics
  • West Nile Virus Vaccines / immunology
  • West Nile Virus Vaccines / therapeutic use*
  • West Nile virus / genetics
  • West Nile virus / immunology*

Substances

  • Antibodies, Viral
  • Vaccines, DNA
  • West Nile Virus Vaccines

Associated data

  • ClinicalTrials.gov/NCT00106769