A Randomized Phase I Safety and Immunogenicity Trial of Live Recombinant Canarypox ALVAC-HIV vCP205 Delivered by Alternate Mucosal Routes in HIV-1 Uninfected Adult Volunteers
Condition: HIV Infections
MeSH terms: HIV Infections
Study type: Interventional
Phase: Phase 1

Summary: 
      To compare the safety of ALVAC-HIV vCP205 to that of ALVAC-RG vCP65 rabies glycoprotein,
      delivered by a variety of mucosal routes. To evaluate the antibody, humoral, and cellular
      immune responses resulting from ALVAC-HIV vCP205. [AS PER AMENDMENT 8/3/98: To obtain safety
      data on AIDSVAX B/B boosting administered by the intramuscular and intranasal routes in the
      context of previous immunization via alternate mucosal routes or intramuscularly with a
      canarypox vector expressing HIV-1 antigens (vCP205). To obtain immunogenicity data on AIDSVAX
      B/B boosting.] One of the earliest observations in the HIV epidemic was the demonstration of
      HIV infection at mucosal surfaces of cells in the genital tract. These data suggest that
      priming of immune defenses of viral infected cells may be an important component in the
      strategy of developing an effective HIV vaccine. Direct immunization of relevant mucosal
      surfaces with a vectored vaccine may stimulate mucosal immunity. The ALVAC-HIV vCP205
      immunogen is constructed from a live recombinant canarypox vector that has a good safety
      profile in volunteers and should allow mucosal induction of immunity.
    

Detailed description: 
      One of the earliest observations in the HIV epidemic was the demonstration of HIV infection
      at mucosal surfaces of cells in the genital tract. These data suggest that priming of immune
      defenses of viral infected cells may be an important component in the strategy of developing
      an effective HIV vaccine. Direct immunization of relevant mucosal surfaces with a vectored
      vaccine may stimulate mucosal immunity. The ALVAC-HIV vCP205 immunogen is constructed from a
      live recombinant canarypox vector that has a good safety profile in volunteers and should
      allow mucosal induction of immunity.

      This randomized, double-blind trial evaluates the safety of and immune response to
      vaccination with ALVAC-HIV vCP205 given at 0, 1, 3, and 6 months. Patients are randomly
      assigned to 1 of 7 drug administration routes as follows:

      Group A: Intramuscular Group B: Oral Group C: Intranasal Group D: Intrarectal Group E:
      Intravaginal Group F: Intranasal/intramuscular Group G: Intrarectal/intramuscular Twelve
      patients are randomized to each group, 8 of whom receive experimental therapy with ALVAC-HIV
      vCP205 and 4 of whom receive control therapy with ALVAC-RG vCP2058 (rabies vaccine). Women
      are preferentially enrolled, with a goal of 60% women (minimum of 4 women per treatment arm);
      only women are randomized to Group E. Blinding is maintained with respect to drug assignment
      rather than route of administration, after randomization. NOTE: The protocol will be amended
      to add 2 boost vaccinations with subunit products at approximately Months 9 and 12 when a
      suitable boost product is identified. [AS PER AMENDMENT 8/3/98: The protocol has been
      modified to include 2 booster vaccinations to be administered at 9 and 12 months. Patients in
      Group A receive booster vaccination with ALVAC-HIV VCP205 or ALVAC-RG intranasally. Patients
      in Groups B through G are boosted with AIDSVAX B/B vaccine (a bivalent vaccine consisting of
      MN rgp120/HIV-1 antigen and GNE8 rgp120/HIV-1 antigen in alum adjuvant) or with Imovax
      diploid cell rabies vaccine; vaccinations for these patients are given intramuscularly.] [AS
      PER AMENDMENT 11/19/98: The second booster vaccination for group A will be administered at
      study Month 15.]
    

Intervention name(s): MN rgp120/HIV-1 and GNE8 rgp120/HIV-1; ALVAC-HIV MN120TMG (vCP205); ALVAC-RG Rabies Glycoprotein (vCP65)
Intervention type(s): Biological; Biological; Biological
Intervention description(s): Dosage will vary based on route of administration; Dosage will vary based on route of administration; Dosage will vary based on route of administration
Intervention MeSH terms: polysaccharide-K
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: Vaccines, Synthetic; Injections, Intramuscular; HIV-1; Immunity, Cellular; AIDS Vaccines; HIV Seronegativity; Mucous Membrane; Antibodies, Viral; Avipoxvirus; Genetic Vectors; HIV Envelope Protein gp120; Immunity, Mucosal; Rabies Vaccines; HIV Preventive Vaccine