title: 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.
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.
  
  
  BACKGROUND
  NCT00300417.
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. ledgerwood@mail.nih.gov
authors.forename: Julie E
authors.initials: JE
authors.lastname: Ledgerwood
authors.forename: Theodore C
authors.initials: TC
authors.lastname: Pierson
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Hubka
authors.forename: Niraj
authors.initials: N
authors.lastname: Desai
authors.forename: Steve
authors.initials: S
authors.lastname: Rucker
authors.forename: Ingelise J
authors.initials: IJ
authors.lastname: Gordon
authors.forename: Mary E
authors.initials: ME
authors.lastname: Enama
authors.forename: Steevenson
authors.initials: S
authors.lastname: Nelson
authors.forename: Martha
authors.initials: M
authors.lastname: Nason
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Gu
authors.forename: Nikkida
authors.initials: N
authors.lastname: Bundrant
authors.forename: Richard A
authors.initials: RA
authors.lastname: Koup
authors.forename: Robert T
authors.initials: RT
authors.lastname: Bailer
authors.forename: John R
authors.initials: JR
authors.lastname: Mascola
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Nabel
authors.forename: Barney S
authors.initials: BS
authors.lastname: Graham
mesh_terms: D000328:Adult; D017677:Age Distribution; D000368:Aged; D057134:Antibodies, Neutralizing / Q000097:blood* / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*; D014901:West Nile Fever / Q000517:prevention & control*; D014902:West Nile virus / Q000276:immunology*; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D019444:Vaccines, DNA; D014765:Viral Vaccines