A Phase II Safety and Immunogenicity Trial of Live Recombinant Canarypox ALVAC-HIV vCP205 With or Without HIV-1 SF-2 RGP120 in HIV-1 Uninfected Adult Volunteers
Condition: HIV Infections
MeSH terms: HIV Infections
Study type: Interventional
Phase: Phase 2

Summary: 
      To expand the available data regarding the safety and immunogenicity of 2 HIV-1 vaccine
      strategies: canarypox vector vCP205, or vCP205 with SF-2 rgp120. [AS PER AMENDMENT 7/2/98: To
      obtain immunogenicity and safety data on gp120 subunits that may induce enhanced neutralizing
      antibody response to primary isolates of HIV-1 in the context of previous immunization with a
      canarypox vector expressing HIV antigens (vCP205). To evaluate cytotoxic T lymphocyte
      responses at 1 and 2 years after initial vaccination with vCP205 plus rgp120 SF-2 or vCP205
      alone.] In previous ALVAC vCP205/SF-2 rgp 120 studies, patients have developed antibodies
      that neutralize homologous laboratory strains; over 50% of patients have developed CD8+
      cytotoxic T-lymphocyte responses to HIV env and gag epitopes at some point in the study. This
      Phase II study seeks to confirm these results among persons at lower or higher risk for HIV
      infection with a new lot of ALVAC vCP205, at a dose that is suitable for potential
      large-scale trials. [AS PER AMENDMENT 7/2/98: Addition of AIDSVAX B/B or AIDSVAX B/E boosts
      starting at least 12 months after receiving rgp120 or ALVAC vaccines may induce enhanced
      neutralizing antibody response as deemed from prior studies and thus is planned as
      "follow-up" therapy.]
    

Detailed description: 
      In previous ALVAC vCP205/SF-2 rgp 120 studies, patients have developed antibodies that
      neutralize homologous laboratory strains; over 50% of patients have developed CD8+ cytotoxic
      T-lymphocyte responses to HIV env and gag epitopes at some point in the study. This Phase II
      study seeks to confirm these results among persons at lower or higher risk for HIV infection
      with a new lot of ALVAC vCP205, at a dose that is suitable for potential large-scale trials.
      [AS PER AMENDMENT 7/2/98: Addition of AIDSVAX B/B or AIDSVAX B/E boosts starting at least 12
      months after receiving rgp120 or ALVAC vaccines may induce enhanced neutralizing antibody
      response as deemed from prior studies and thus is planned as "follow-up" therapy.]

      Volunteers are recruited and screened; those who are enrolled are then stratified by their
      risk status into 2 groups: individuals having lower-risk behavior for HIV and individuals
      having higher-risk behavior for HIV. Volunteers are then randomly assigned to arm A, B, or C
      and receive immunizations at months 0, 1, 3, and 6 as follows:

      Group A- ALVAC vCP205 plus SF-2 rgp120 in MF59. Group B- ALVAC vCP205 plus saline placebo.
      Group C- Placebo-ALVAC plus saline placebo. [AS PER AMENDMENT 7/2/98: Beginning 12-18 months
      after initial vaccination, then 2, 6, and 12 months later, 10 volunteers from group A receive
      saline placebo, while 50 volunteers each from groups B and C are rerandomized within their
      respective groups, and are treated as follows.

      Group B (subgroup 1) - AIDSVAX B/B. Group B (subgroup 2) - AIDSVAX B/E. Group B (subgroup 3)
      - alum placebo. Group C (subgroup 1) - AIDSVAX B/B. Group C (subgroup 2) - AIDSVAX B/E. Group
      C (subgroup 3) - alum placebo.] Volunteers are followed for 2 years and are tested for
      humoral immune response to HIV-1. Neutralizing activity to HIV-1 is performed on a subset of
      volunteers monitored for CTL response. [AS PER AMENDMENT 7/2/98: Volunteers receiving AIDSVAX
      B/B and AIDSVAX B/E will additionally be studied for formation of various neutralizing
      antibodies and parameters of cellular immunity.] [AS PER AMENDMENT 4/30/99: Because the
      subunit boosts that were added in version 3.0 are not available, the subunit boost portion of
      version 3.0 is cancelled.]
    

Intervention name(s): MN rgp120/HIV-1 and GNE8 rgp120/HIV-1; MN rgp120/HIV-1 and A244 rgp120/HIV-1; ALVAC-HIV MN120TMG (vCP205); rgp120/HIV-1 SF-2
Intervention type(s): Biological; Biological; Biological; Biological
Masking: Double
Primary purpose: Prevention
Keywords: Vaccines, Synthetic; AIDS Vaccines; HIV Seronegativity; Avipoxvirus; HIV Preventive Vaccine