A Phase I, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Safety and Immunogenicity of HIV-1 MN rsgp120 and Bivalent AIDSVAX B/E (HIV-1 MN rgp120/A244 rgp120) in Combination With QS-21 With or Without Alum in Healthy HIV-1 Uninfected Adults
Condition: HIV Infections
MeSH terms: HIV Infections
Study type: Interventional
Phase: Phase 1

Summary: 
      To assess the safety and immune response to two experimental vaccines when formulated with
      QS-21 or QS-21 plus alum. To determine whether the new preparation of QS-21 in polysorbate 80
      is less reactogenic than the QS-21 formulation used in AVEG Protocols 016, 016A, and 016B. To
      examine whether QS-21 is immunologically equivalent to that used in 16B. To determine if
      QS-21, when given with low doses of antigen, induces measurable HIV-1-specific CTL activity.
      To evaluate if the QS-21 dose-sparing effect extends to an antigen dose of 0.5 micrograms. To
      determine if the bivalent vaccine gives responses equivalent to the monovalent product or if
      a broadening of the HIV-1-specific binding and neutralizing antibody responses occurs.

      An effective vaccine to prevent HIV-1 infection may need to generate diverse and multifaceted
      immunologic responses. Required parts of the immune response may include: humoral antibodies,
      which broadly neutralize non-syncytium-inducing strains of HIV-1; T cell help provided by
      both CD4 and CD8 positive subsets; and a class I-restricted cytotoxic lymphocyte response.
      Other effector responses, such as the generation of antibody-dependent cellular cytotoxicity,
      cytokines, chemokines, or other antiviral factors may also be critical in mounting protective
      immunity. Given the lack of a surrogate immunologic marker, the most practical approach for
      possible efficacy trials would be to evaluate a candidate vaccine that elicits as many of
      these responses as possible.
    

Detailed description: 
      An effective vaccine to prevent HIV-1 infection may need to generate diverse and multifaceted
      immunologic responses. Required parts of the immune response may include: humoral antibodies,
      which broadly neutralize non-syncytium-inducing strains of HIV-1; T cell help provided by
      both CD4 and CD8 positive subsets; and a class I-restricted cytotoxic lymphocyte response.
      Other effector responses, such as the generation of antibody-dependent cellular cytotoxicity,
      cytokines, chemokines, or other antiviral factors may also be critical in mounting protective
      immunity. Given the lack of a surrogate immunologic marker, the most practical approach for
      possible efficacy trials would be to evaluate a candidate vaccine that elicits as many of
      these responses as possible.

      Volunteers in each of 5 groups receive vaccine or placebo by intramuscular injection at
      Months 0, 1, and 6. All patients receive one of two doses of QS-21 along with vaccine or
      placebo and some groups receive alum as follows:

      Group 1: low-dose MN rsgp120/HIV-1 plus QS-21 (13 volunteers). Group 2: high-dose MN
      rsgp120/HIV-1 plus QS-21 (13 volunteers). Group 3: AIDSVAX B/E (injection contains each of
      the two vaccine components, HIV-1 MN rgp120 and A244 rgp120/HIV-1) plus QS-21 plus alum (13
      volunteers).

      Group 4: high-dose MN rgp120/HIV-1 plus QS-21 plus alum (13 volunteers). Group 5: placebo
      plus QS-21 (8 volunteers). Volunteers will be closely monitored after each immunization and
      followed for a minimum of 12 months after the initial immunization.
    

Intervention name(s): MN rgp120/HIV-1 and A244 rgp120/HIV-1; QS-21; rgp120/HIV-1MN
Intervention type(s): Biological; Biological; Biological
Masking: Double
Primary purpose: Prevention
Keywords: Vaccines, Synthetic; HIV Antibodies; HIV Antigens; HIV-1; Adjuvants, Immunologic; AIDS Vaccines; T-Lymphocytes, Cytotoxic; HIV Seronegativity; HIV Envelope Protein gp120; Alum Compounds; HIV Preventive Vaccine