HIV-1 Vaccine Booster in Previously Immunized Uninfected Adult Volunteers
Condition: Healthy; HIV Infections
MeSH terms: HIV Infections
Study type: Interventional
Phase: Phase 1

Summary: 
      This study will test the safety and side effects of an experimental vaccine booster against
      HIV. A vaccine is a substance given to try to create immunity or resistance to a disease or
      infection. The vaccine used in this study is called VRC-HIVADV014-00-VP. It is made from an
      adenovirus (a common virus that causes upper respiratory infections) that contains DNA
      (genetic material) of three HIV proteins. Injected into a human, the viral DNA instructs the
      body to make small amounts of some HIV proteins. VRC-HIVADV014-00-VP will be given to people
      who previously received a vaccine called VRC-HIVDNA009-00-VP under NIH protocol 03-I-0022.
      Important: Study participants cannot catch an adenovirus infection or HIV or AIDS from the
      vaccine or any proteins made from it.

      Healthy normal volunteers who participated in NIH protocol 03-I-0022 may be eligible for this
      study. They must have completed three injections of 4 mg or 8 mg of VRC-HIVDNA009-00-VP
      without experiencing a serious side effect that was possibly related to the vaccine.
      Candidates are screened with a medical history, clinical evaluation, blood and urine tests,
      and HIV and pregnancy counseling.

      Participants receive one injection of VRC-HIVADV014-00-VP the day they enroll in the study
      (study day 0). They are observed for at least 30 minutes after immunization. At home, they
      record their temperature and any symptoms they may experience, including any effects at the
      injection site, for 5 days and call a study nurse 1 or 2 days after the injection. They
      immediately report any symptoms to the clinic staff and, if necessary, come to the clinic for
      an examination.

      Participants have five additional clinic visits during the study, at weeks 2, 4, 6, 12 and
      24, each lasting about 2 hours. At each visit, they are checked for health changes or
      problems and are asked about medications they are taking. Blood is drawn for immune function
      testing, HLA typing (a genetic test of immune system markers), and other genetic factors. A
      urine sample is collected at some visits. Additional laboratory tests may be requested
      between visits. Some participants may undergo apheresis at the week 4 visit to collect a
      large number of white blood cells for laboratory tests to see how the immune system responds
      to the study vaccine. For this procedure, blood is collected through a needle in an arm vein
      and flows through a catheter (plastic tube) into a machine that separates it into its
      components by centrifugation (spinning). The white cells are extracted and the rest of the
      blood is returned through another needle in the other arm. The procedure takes about 1 to 3
      hours.

      Participants are tested three or more times for HIV and are questioned about their sexual
      behavior and drug use. They complete a "social impact" questionnaire at week 24 that includes
      questions about any problems they may have experienced from their participation in the study
      regarding such things as insurance, health care, friends, family, employment, housing,
      education, or government agencies.
    

Detailed description: 
      Study Design: This is a Phase I open-label study to examine safety, tolerability and immune
      response of a multiclade HIV adenoviral vector vaccine as a booster vaccination in uninfected
      adults. The hypothesis is that this vaccine will be safe as a booster vaccine and elicit
      immune responses to HIV. The primary objective is to evaluate the safety and tolerability of
      a VRC-HIVADV014-00-VP booster vaccination in uninfected subjects who previously received 3
      injections of VRC-HIVDNA009-00-VP more than one year prior to the study vaccination. The
      secondary objectives include immunogenicity evaluations and adenovirus serotype 5 (Ad5)
      antibody titers, and social impacts. Exploratory evaluations include epitope mapping and
      other immunogenicity evaluations.

      Product Description: VRC-HIVADV014-00-VP is a recombinant product composed of 4 adenoviral
      vectors (Ad) (in a 3:1:1:1 ratio) that encode the HIV-1 Gag/Pol polyprotein from clade B and
      HIV-1 Env glycoproteins from clades A, B, and C, respectively.

      Subjects: Healthy adult volunteers who previously received three injections of
      VRC-HIVDNA009-00-VP at a dosage of 4 mg or 8 mg in the VRC 004 study (03-I-0022): subjects in
      these groups were between 20 and 39 years old at time of enrollment in VRC 004; those who
      participate in VRC 009 will be approximately 1-3 years older at the time of enrollment into
      VRC 009.

      Study Plan: Up to thirty-two volunteers will receive one 1 mL injection of the study agent at
      a dosage of 1 x 10(10) PU IM in a deltoid muscle. Safety and immunogenicity will be evaluated
      by follow-up visits over the subsequent 24 weeks. The peripheral blood mononuclear cell
      (PBMC) sample for immunogenicity studies collected at Week 4 after vaccination will be
      obtained by apheresis if the subject is willing and eligible for apheresis and an apheresis
      appointment can be conveniently scheduled in the interval specified; otherwise PBMCs will be
      obtained from 80 mL blood collected by phlebotomy.

      Study Duration: Subjects will be evaluated at 6 or more clinical visits for 24 weeks after
      the study injection.

      Study Endpoints: The primary endpoint is safety of the vaccine administered at a dose of 1 x
      10(10) particle units (PU) by intramuscular injection. Secondary endpoints are immunogenicity
      as indicated by HIV-specific antibody and cellular immune responses through Week 6, Ad5
      antibody titer at Week 0 and Week 4 and social impact at Week 24. Exploratory analyses of
      immunogenicity at Weeks 12 and 24, Ad5 antibody titer at Week 24 and epitope mapping of the
      CD8+ and CD4+ T cell responses at Week 4.
    

Intervention name(s): VRC-HIVADV014-00-VP booster; VRC-HIVADV014-00-VP
Intervention type(s): Biological; Drug
Primary purpose: Treatment
Keywords: HIV-Negative; Healthy; Immunity; Preventive; Virus; Healthy Volunteer; HV