Safety of and Immune Response to a DNA HIV Vaccine Followed by an Adenoviral Vaccine Boost Given Three Different Ways to HIV Uninfected Adults
Condition: HIV Infections
MeSH terms: HIV Infections
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to determine the safety of, immune response to, and tolerability
      of an adenoviral vector HIV vaccine given after a three-dose regimen of a DNA HIV vaccine.
      The adenoviral vaccine will be given into arm muscle (intramuscularly), between skin layers
      (intradermally), or under the skin (subcutaneously).

      NOTE: In October 2007, vaccinations with the adenoviral vaccine, VRC-HIVADV014-00-VP, were
      discontinued. In December 2007, vaccinations with the DNA vaccine were also discontinued.
      Participants will be followed for safety and immune responses at regular study visits.
    

Detailed description: 
      One factor that may affect safety and immunogenicity to an HIV vaccine is the route of
      vaccine administration. Administration into the skin (intradermal) or subcutaneous tissue may
      be more immunogenic or provide a different pattern of immune responses than administration by
      the intramuscular route. Previous studies with other preventive vaccines suggest that the
      resulting immunogenicity following intradermal or subcutaneous vaccine administration is
      comparable or better than immunogenicity observed following intramuscular administration.
      Increased immunogenicity though use of a particular route will likely result in greater
      demonstrated efficacy, requiring fewer or lower doses of vaccine to elicit a sufficient
      immune response.

      The DNA HIV vaccine VRC-HIVDNA009-00-VP has shown immunogenicity in multiple clinical trials;
      in one trial, the DNA vaccine demonstrated a nearly 100% CD4 T-cell response rate. The
      adenoviral vector HIV vaccine VRC-HIVADV014-00-VP has shown immunogenicity when given
      intramuscularly and has appeared safe and well tolerated in prior vaccine trials in HIV
      uninfected adults. The DNA plasmids in both vaccines code for proteins from HIV subtypes A,
      B, and C. This study will evaluate the safety, immunogenicity, and tolerability to a DNA HIV
      vaccine, followed by an adenoviral vaccine boost given either intramuscularly, intradermally,
      or subcutaneously, in HIV uninfected adults.

      All participants will receive three doses of the DNA vaccine intramuscularly at study entry
      and Months 1 and 2. Participants will be randomly assigned to one of three groups, differing
      by how they will receive the adenoviral vaccine boost:

        -  Group 1 participants will receive the vaccine boost intramuscularly at Month 6

        -  Group 2 participants will receive the vaccine boost intradermally at Month 6

        -  Group 3 participants will receive the vaccine boost subcutaneously at Month 6

      This study will last 1 year. There will be 12 study visits; a physical exam, medication
      history, and risk reduction/pregnancy prevention compliance counseling will occur at all
      visits. Urine and blood collection will occur at selected visits. Participants will be asked
      to complete a social impact assessment at Months 2, 6, and 12 and an outside testing and
      belief questionnaire at Months 6 and 12. Participants will be asked to record their
      temperature and other side effects in a symptom log on the day of each vaccination and for 3
      days thereafter to report any side effects.

      NOTE: In October 2007, vaccinations with the adenoviral vaccine, VRC-HIVADV014-00-VP, were
      discontinued. In December 2007, vaccinations with the DNA vaccine were also discontinued.
      Participants will be followed for safety and immune responses at regular study visits and
      will be asked to continue in long term follow-up for purposes of safety surveillance to a
      total of 5 years following initial vaccination
    

Intervention name(s): VRC-HIVDNA009-00-VP; VRC-HIVADV014-00-VP
Intervention type(s): Biological; Biological
Intervention description(s): HIV DNA vaccine containing the HIV genes gag, pol, nef, and env A,B, and C. The HIV DNA vaccine will be given in three doses intramuscularly at study entry and Months 1 and 2; Adenoviral vector HIV booster vaccine containing the HIV genes gag, pol, and env. The adenoviral vector HIV booster vaccine will be administered intramuscularly (Group 1), intradermally (Group 2), or subcutaneously (Group 3) at Month 6
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: HIV Seronegativity; Adenoviral Vector Vaccine; DNA Plasmid Vaccine; HIV Preventive Vaccine