Vaccine to Prevent West Nile Virus Disease
Condition: Healthy; West Nile Fever; Healthy Volunteer; HV
MeSH terms: West Nile Fever
Study type: Interventional
Phase: Phase 1

Summary: 
      This study will test the safety of an experimental vaccine intended to prevent West Nile
      virus (WNV) infection and determine if it causes side effects. WNV symptoms may vary from
      fever and headache, to a polio-like syndrome with paralysis. Infection rarely results in
      death. The vaccine used in this study contains DNA that instructs the body to produce a small
      amount of a protein found in WNV. If the body creates resistance or immunity to these
      proteins, then the vaccine may protect against WNV. Study participants cannot get WNV from
      the vaccine.

      Healthy volunteers between 18 years and 50 years of age may be eligible for this study.
      Candidates are screened with a medical history, physical examination, and blood and urine
      tests, including a pregnancy test for women who can become pregnant. Patients undergo the
      following tests and procedures:

        -  Vaccine injections: Vaccines are given as injections in the upper arm, using a
           needleless system called the Biojector 2000. The first injection is on study day 0, the
           second on day 28 (+/-) 7 days, and the third on day 56 (+/-) 7 days. There must be at
           least 21 days between injections. The pregnancy test for women of childbearing potential
           is repeated the day of each vaccine injection.

        -  Diary card: Participants are given a 5-day diary card after each injection to record
           their temperature and any symptoms and side effects they may experience for up to 5 days
           after the injection. The diary cards are returned to the clinic at visits scheduled 2
           weeks after each injection. Side effects and symptoms also must be reported immediately
           to a study nurse or doctor, and a clinic visit may be required for an examination.

        -  Clinic visits: At day 0 and weeks 2, 4, 6, 8, 10, 12, 24 and 32, participants have a
           medical history, physical examination (if needed) and blood tests. Vital signs and
           weight are also recorded. Lymph nodes are examined at day 0 and weeks 2, 4, 6, 8, 10 and
           12, and urine samples are collected at day 0 and weeks 2, 4, 6, 8 and 10.

      Some of the blood drawn during this study is used for genetic tests to see if different types
      of immune response to a vaccine are related to genetic differences in people.
    

Detailed description: 
      Study Design: This is a Phase I open label study to evaluate safety, tolerability, and immune
      response of a recombinant DNA vaccine, VRC-WNVDNA017-00-VP. The hypothesis is that this
      regimen will be safe for human administration and elicit immune responses to the West Nile
      virus. The primary objective is to evaluate the safety and tolerability in humans of the
      investigational vaccine. Secondary and exploratory objectives are related to the
      immunogenicity of the study vaccine.

      Product Description: VRC-WNVDNA017-00-VP is composed of a single closed circular DNA plasmid
      that encodes the WNV viral proteins precursor transmembrane (PrM) and envelope (E). Vaccine
      vials will be supplied at 4 mg/mL. Each DNA vaccination will be 1 mL of vaccine administered
      intramuscularly (in deltoid muscle) using the Biojector 2000 Needle-Free Injection Management
      System.

      Subjects: Healthy adult volunteers (18 to 50 years old) will be enrolled.

      Study Plan: Fifteen volunteers will be enrolled and receive 3 injections on the schedule
      shown in the schema. The protocol requires nine clinic visits and three telephone follow-up
      contacts.

      Study Duration: 32 weeks clinical follow-up for each participant.

      Study Endpoints: The primary endpoint is safety of the regimen; secondary immunogenicity
      endpoints are an ELISPOT and an intracellular cytokine staining (ICS) assay for WNV-specific
      T cell responses and a WNV ELISA assay. The principal timepoints for ICS and ELISPOT are Week
      0 (baseline), Week 8 and Week 12. ICS and ELISPOT at other study timepoints, as well as other
      immunogenicity assays through Week 32, will be completed as exploratory evaluations. Stored
      sera will be tested for WNV neutralizing antibody once an assay is developed.
    

Intervention name(s): VRC-WNVDNA017-00-VP
Intervention type(s): Drug
Primary purpose: Treatment
Keywords: Flavivirus; Mosquito; Immunity; Preventive; Virus; West Nile Fever; Healthy Volunteer; HV