A Multicenter, Randomized, Placebo-Controlled, Double-Blind Trial to Evaluate the Safety and Immunogenicity of a Recombinant Vaccinia-HIV-1 IIIB Env/Gag/Pol Vaccine (TBC-3B)
Condition: HIV Infections
MeSH terms: Vaccinia
Study type: Interventional
Phase: Phase 1

Summary: 
      To evaluate, in healthy HIV-1 seronegative vaccinia-immune and vaccinia-naive volunteers, the
      safety and immunogenicity of an HIV-1 candidate vaccine (TBC-3B) consisting of a live
      recombinant vaccinia virus expressing the env, gag, and pol genes of HIV-1 IIIB strain. To
      evaluate the potential of boosting with one of a variety of HIV-1 recombinant subunit,
      peptide, or pseudovirion vaccines, if available, to augment the immune responses of the
      vaccinees.

      Antigenic drift, defined as the genetic variation of the HIV-1 envelope gene that results in
      antigenic variation during natural infection, may confound attempts to achieve protective
      immunity using a vaccine based solely on HIV-1 envelope proteins. Inclusion of conserved core
      and polymerase proteins along with envelope protein in a candidate vaccine may address some
      of the problems with antigenic variability. A prime-boost immunization approach using a novel
      priming immunogen expressing env, gag, and pol genes of the HIV-1 IIIB strain will be
      attempted in this study.
    

Detailed description: 
      Antigenic drift, defined as the genetic variation of the HIV-1 envelope gene that results in
      antigenic variation during natural infection, may confound attempts to achieve protective
      immunity using a vaccine based solely on HIV-1 envelope proteins. Inclusion of conserved core
      and polymerase proteins along with envelope protein in a candidate vaccine may address some
      of the problems with antigenic variability. A prime-boost immunization approach using a novel
      priming immunogen expressing env, gag, and pol genes of the HIV-1 IIIB strain will be
      attempted in this study.

      In Part I, vaccinia-immune volunteers are randomized to one of two regimens. Group A receives
      priming with TBC-3B on days 0 and 56, followed by boosting on day 224 (8 months) with one of
      the following: TBC-3B, an alternative immunogen such as pseudovirion particles or a
      recombinant HIV-1 subunit or peptide vaccine, or placebo. Group B receives priming with
      control vaccine (DryVax), followed by boosting with an appropriate placebo. At least 50
      percent of subjects in Part I will be observed for a minimum of 8 weeks before subsequent
      volunteers are enrolled in Part II. PER 11/18/94 AMENDMENT, Part I boosting is given on day
      392. PER 5/19/95 AMENDMENT, Part I boosting is given on day 756 if not available on day 392;
      if the appropriate product is not available then, the study will end on day 756. In Part II,
      vaccinia-naive volunteers are randomized to one of three regimens. Group C receives TBC-3B on
      day 0 and saline placebo on day 56. Group D receives TBC-3B on days 0 and 56. Both Group C
      and D receive boosting with TBC-3B or an alternative immunogen on day 224. Group E receives
      control vaccine (DryVax) on days 0 and 56, followed by appropriate placebo on day 224. Per
      06/10/94 addendum, volunteers will be contacted once or twice per year for at least 5 years
      to check on health status.

      NOTE: Part I (Part A) of the protocol has closed to accrual.
    

Intervention name(s): TBC-3B Vaccine; Smallpox Vaccine
Intervention type(s): Biological; Biological
Intervention MeSH terms: Vaccines
Masking: Double
Primary purpose: Prevention
Keywords: Vaccines, Synthetic; Vaccinia Virus; Viral Vaccines; Smallpox Vaccine; HIV-1; AIDS Vaccines; HIV Seronegativity; HIV Preventive Vaccine