VRC 705: A Zika Virus DNA Vaccine in Healthy Adults and Adolescents
Condition: Zika Virus; Zika Virus Infection; Virus Diseases; Flavivirus Infections; Flaviviral Diseases; Flaviviridae Infections; RNA Virus Infections
MeSH terms: Infections; Communicable Diseases; Virus Diseases; Zika Virus Infection; RNA Virus Infections; Flaviviridae Infections; Flavivirus Infections
Study type: Interventional
Phase: Phase 2

Summary: 
      This was a multicenter, randomized study to evaluate the safety, immunogenicity, and efficacy
      of VRC-ZKADNA090-00-VP (Zika virus wildtype DNA vaccine) or placebo. In Part A, the primary
      objective was to evaluate the safety and tolerability of the vaccine in different vaccination
      regimens. In Part B, the primary objectives were to evaluate the safety and efficacy of the
      vaccine compared to placebo.
    

Detailed description: 
      This was a multicenter, randomized study to evaluate safety, immunogenicity, and efficacy of
      a 3-dose vaccination regimen with the Zika virus wildtype (ZIKVwt) DNA vaccine
      (VRC-ZKADNA090-00-VP) or placebo (VRC-PBSPLA043-00-VP). The placebo was a sterile
      phosphate-buffered saline (PBS). The hypotheses were that the ZIKVwt DNA vaccine would be
      safe and would elicit a ZIKV-specific immune response.

      Participants received study product intramuscularly (IM) in the limbs as specified by the
      group assignment by PharmaJet needle-free device. In Part A, 90 participants were randomized
      to vaccine at a 1:1:1 ratio to receive a 4 mg dose split between 2 injections, 4 mg dose
      split between 4 injections or 8 mg dose split between 4 injections. In Part B, 2338
      participants were randomized to vaccine or placebo in a 1:1 ratio to receive a 4 mg (1 mL)
      dose of vaccine or 1 mL of placebo split between 2 injections. The vaccine dose and
      administration plan for Part B was selected based on Part A and Phase 1 data.

      Vaccine safety and tolerability were assessed by monitoring of clinical and laboratory
      parameters throughout the study. Solicited reactogenicity symptoms were collected for 7 days
      after each product administration. The study schedule included clinic visits with safety and
      immunogenicity blood samples collected at particular time points.

      Vaccine efficacy was evaluated in Part B by comparing incidence of virologic ZIKV cases
      between vaccine and placebo groups. During the study, when participants exhibited any
      possible symptom of ZIKV infection, they were evaluated by blood and urine ZIKV polymerase
      chain reaction (PCR). Stored blood samples were also assessed retrospectively by ZIKV PCR to
      identify possible asymptomatic cases. A Data and Safety Monitoring Board (DSMB) oversaw the
      study.
    

Intervention name(s): VRC-ZKADNA090-00-VP; VRC-PBSPLA043-00-VP
Intervention type(s): Biological; Other
Intervention description(s): VRC-ZKADNA090-00-VP is composed of a single closed-circular DNA plasmid (VRC 5283) that encodes with wild type (wt) precursor transmembrane M (prM) and envelope (E) proteins from the H/PF/2013 strain of ZIKV; A sterile phosphate-buffered saline (PBS) prepared for human administration as a placebo
Other intervention name(s): Placebo
Allocation: Randomized
Intervention model: Sequential Assignment
Intervention model description: Part A participants (n=90) were randomized to study groups at a 1:1:1 ratio to receive a 4 mg or 8 mg dose of vaccine split between 2 or 4 injections. In Part B, participants (n=2338) were randomized to vaccine or placebo in a 1:1 ratio to receive a 4 mg (1 mL) dose of vaccine or 1 mL of placebo split between 2 injections. The vaccine dose and number of injections in Part B was determined by preliminary data from the Phase 1 trial and from Part A.
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Flavivirus; Zika; Vaccine; Physiological Effects of Drugs; Immunologic Factors; Virus-like Particles; Zika vaccine