A Phase 1 clinical trial of a DNA vaccine for Venezuelan equine encephalitis delivered by intramuscular or intradermal electroporation

Vaccine. 2016 Jun 30;34(31):3607-12. doi: 10.1016/j.vaccine.2016.04.077. Epub 2016 May 17.

Abstract

Venezuelan equine encephalitis virus (VEEV), a mosquito-borne alphavirus, causes periodic epizootics in equines and is a recognized biological defense threat for humans. There are currently no FDA-licensed vaccines against VEEV. We developed a candidate DNA vaccine expressing the E3-E2-6K-E1 genes of VEEV (pWRG/VEE) and performed a Phase 1 clinical study to assess the vaccine's safety, reactogenicity, tolerability, and immunogenicity when administered by intramuscular (IM) or intradermal (ID) electroporation (EP) using the Ichor Medical Systems TriGrid™ Delivery System. Subjects in IM-EP groups received 0.5mg (N=8) or 2.0mg (N=9) of pWRG/VEE or a saline placebo (N=4) in a 1.0ml injection. Subjects in ID-EP groups received 0.08mg (N=8) or 0.3mg (N=8) of DNA or a saline placebo (N=4) in a 0.15ml injection. Subjects were monitored for a total period of 360 days. No vaccine- or device-related serious adverse events were reported. Based on the results of a subject questionnaire, the IM- and ID-EP procedures were both considered to be generally acceptable for prophylactic vaccine administration, with the acute tolerability of ID EP delivery judged to be greater than that of IM-EP delivery. All subjects (100%) in the high and low dose IM-EP groups developed detectable VEEV-neutralizing antibodies after two or three administrations of pWRG/VEE, respectively. VEEV-neutralizing antibody responses were detected in seven of eight subjects (87.5%) in the high dose and five of eight subjects (62.5%) in the low dose ID-EP groups after three vaccine administrations. There was a correlation between the DNA dose and the magnitude of the resulting VEEV-neutralizing antibody responses for both IM and ID EP delivery. These results indicate that pWRG/VEE delivered by either IM- or ID-EP is safe, tolerable, and immunogenic in humans at the evaluated dose levels. Clinicaltrials.gov registry number NCT01984983.

Keywords: Clinical trial; DNA vaccine; Electroporation; Human; Intradermal; Intramuscular; Phase 1; Venezuelan equine encephalitis.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood
  • Double-Blind Method
  • Electroporation
  • Encephalitis Virus, Venezuelan Equine
  • Encephalomyelitis, Venezuelan Equine / prevention & control*
  • Female
  • Humans
  • Immunogenicity, Vaccine
  • Injections, Intradermal
  • Injections, Intramuscular
  • Male
  • Middle Aged
  • Vaccines, DNA / administration & dosage*
  • Vaccines, DNA / therapeutic use
  • Viral Vaccines / administration & dosage*
  • Viral Vaccines / therapeutic use
  • Young Adult

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Vaccines, DNA
  • Viral Vaccines

Associated data

  • ClinicalTrials.gov/NCT01984983