Immune Responses to Two Experimental HIV Vaccines in Healthy Adults
Condition: HIV Negative; Adaptive Immunity; Innate Immunity
Study type: Interventional
Phase: Phase 1

Summary: 
      Background:

      The primary focus of the Vaccine Research Center (VRC) at the NIH is to develop vaccines for
      HIV/AIDS. The main purpose of this study is to look in detail at the body s immune response
      to two experimental HIV vaccines currently in development at the VRC. One is known as the
      rAd5 vaccine and the other is known as the DNA vaccine. These vaccines are made with pieces
      of manufactured DNA. They do not contain live or killed HIV. It is impossible for study
      vaccines to give you HIV and they cannot cause you to give HIV to someone else. Both of these
      experimental vaccines have been given to people before in other research studies. They have
      not been approved for treating or preventing HIV infection.

      Purpose:

      The main purpose of this study is to look in detail at the body s immune responses after the
      experimental HIV vaccines are given and to assess safety of the study vaccines.

      Eligibility:

      Healthy volunteers between the ages of 18 and 50 who are not infected with HIV and who meet
      the eligibility requirements.

      Design:

      Participants will be screened with a medical history (including questions about sexual
      history and drug use), physical exam, and blood tests.

      The study will have two groups:

      <TAB>One group will receive one injection of the rAd5 vaccine, and have 8 clinic visits over
      3 months.

      <TAB>The second group will have three injections of the DNA vaccine, one injection of the
      rAd5 vaccine, and have 12 clinic visits over 6 months.

      All participants will be asked to provide blood and body fluid samples for testing during the
      study.

      Payment for participation will be provided....
    

Detailed description: 
      Study Design:

      This is a hypothesis-generating descriptive study to evaluate the kinetics and pattern of
      early innate and adaptive immune responses to the VRC recombinant adenoviral vector serotype
      5 vaccine, VRC-HIVADV014-00-VP (rAd5). The rAd5 vaccine has been previously administered to
      more than 1000 study subjects and characterized as safe and immunogenic. A difference in the
      pattern of vaccine antigen-specific immune responses observed when rAd5 is given as a single
      agent compared to after priming by a 6-plasmid DNA vaccine, VRCHIVDNA016-00-VP, has
      previously been reported. This study will randomize vaccine-naive subjects to receive a
      single injection of rAd5 or to the DNA primerAd5 boost regimen that is now in a large Phase
      II study. Collection of blood, rectal, oral and genital specimens for characterization of
      early innate and adaptive immune responses will follow receipt of rAd5. The hypothesis is
      that the pattern of early innate and adaptive immune responses elicited by the rAd5 vaccine
      administered after priming with DNA vaccine will be distinctly different from the pattern
      elicited when rAd5 is administered as a single agent. The primary objectives are to describe
      the kinetics and pattern of early innate and adaptive immune responses that occur in blood
      samples early after administration of rAd5 vaccine alone and after administration following 3
      DNA prime injections. Secondary and exploratory objectives are related safety, as well as the
      pattern of immune responses in mucosal samples and in blood samples.

      Product Description:

      VRC-HIVDNA016-00-VP [6-plasmid DNA vaccine] is composed of 6 closed, circular DNA plasmids
      that encode for HIV-1 Gag, Pol and Nef proteins (from clade B) and Env glycoproteins from
      clade A, clade B, and clade C, which are combined in equal proportions. All injections will
      be at 4 mg dose in a 1 mL volume administered intramuscularly (IM) by Biojector (registered
      trademark) into deltoid muscle.

      VRC-HIVADV014-00-VP (rAd5 vaccine) is composed of 4 recombinant nonreplicating adenoviral
      vectors that encode for HIV-1 Gag/Pol polyproteins (from clade B) and Env glycoproteins from
      clade A, clade B, and clade C, which are combined in a 3:1:1:1 ratio, respectively, in a
      final formulation buffer (FFB). All injections will be at 10(10) PU dose in a 1 mL volume
      administered IM by needle and syringe into deltoid muscle.

      Subjects:

      The study target accrual is at least 20 subjects who complete collection of blood, oral,
      rectal and genital specimens through 2 weeks after the rAd5 vaccination. To account for
      potential discontinuations from the study, enrollment may include up to 36 HIV-uninfected
      adults, ages 18-50 years old that are HIV vaccine-naive and adenovirus serotype 5 (Ad5)
      antibody negative at screening; males must be fully circumcised.

      Study Plan:

      Subjects will be randomized at a 1:1 ratio to receive a single injection of rAd5 or the DNA
      prime-rAd5 boost schedule and will be stratified by gender to achieve approximately equal
      distribution of each gender into the two vaccination schedules. Subjects randomized to Group
      1 may receive the vaccination on enrollment day or schedule the day of vaccination to occur
      within 6 weeks followed by the expected 24 hours in the inpatient unit and day 3
      post-vaccination sample collections for the frequent sampling that will immediately ensue
      according to the sample collection schedule. Subjects randomized to Group 2 will receive the
      first of three DNA vaccinations and schedule projected dates for the subsequent injections
      and timepoints with intensive sample collection schedules. Due to the need to commit to about
      3 days of disruption in normal daily activities, starting with the day of rAd5 vaccination on
      either schedule, flexibility in scheduling of the rAd5 vaccination is included in the
      protocol plan.

      Subjects from both groups will be admitted to the NIH Clinical Center overnight for the first
      24 hours following vaccination with rAd5. On the rAd5 vaccination day, peripheral blood
      samples will be collected for serum, plasma and peripheral blood mononuclear cells at seven
      target time points in the first 24 hours as follows: pre-injection and post-injection hours
      1, 3, 6, 12, 18 and 24; then days 3, 5, 7, 14 and 28 post-rAd5 vaccine. Mucosal sampling will
      occur on day 14 after rAd5 vaccine. This will include buccal mucosa, rectal secretions,
      cervical secretions (from women) and semen samples (from men). There will be a blood
      collection to assess innate immunity following the 3rd DNA vaccination in Group 2 with blood
      draws at pre-injection and at post-injection hours 1, 3, 6 and 18.

      The safety of vaccinations and the research plan will be monitored by a protocol safety
      review team.

      Study Duration:

      Subjects will be followed in the clinic through 12 weeks after last study injection and
      contacted for long term follow-up 12 weeks later and then every 48 weeks through Study Week
      144.
    

Intervention name(s): VRC-HIVDNA016-00-VP; VRC-HIVADV014-00-VP
Intervention type(s): Biological; Biological
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: HIV-uninfected; Mucosal Immunity; Kinetics; Cytokines; Chemokines; Healthy Volunteer; HV