A Phase I Multicenter, Randomized, Double-Blind Trial to Evaluate the Safety and Immunogenicity of Recombinant Vaccinia Virus Expressing the Envelope Glycoproteins of Human Immunodeficiency Virus
Condition: HIV Infections
MeSH terms: HIV Infections; Acquired Immunodeficiency Syndrome; Vaccinia; Immunologic Deficiency Syndromes
Study type: Interventional
Phase: Phase 1

Summary: 
      Evaluation of the safety and immunogenicity (immunological reactivity) of HIVAC-1e vaccine.
      An additional goal is to determine which dose level of vaccine might be most effective.
      Specific questions to be addressed in this part of the study include: Are there adverse
      reactions to gp160 vaccine when given to vaccinees previously immunized with a
      vaccinia-recombinant? Does gp160 vaccination of prior HIVAC-1e vaccine result in stimulation
      of neutralizing antibody and other humoral immune responses? Does vaccination with gp160
      enhance the development of cell-mediated immune responses in HIVAC-1e vaccinees? Is the
      magnitude of immune response to gp160 booster immunization greater following priming with
      GP160 recombinant vaccinia (HIVAC-1e) vaccination than priming with three doses of purified
      recombinant gp160? AMENDED: An 80 mcg dose of gp160 has been chosen for the booster because
      this dose has been shown to be safe and immunogenic in previous trials and allows comparison
      of the late boost in this protocol with the late boost in the protocol in which patients were
      primed with three doses of gp160. Original design: HIVAC-1e vaccine is a preparation of the
      envelope protein of HIV (the virus that causes AIDS). The protein is produced by genetic
      modification in vaccinia virus. The purpose of a vaccine is to produce an artificially
      increased immunity to a particular disease, in this case, AIDS. Since there is no known cure
      for AIDS, the control of this disease necessitates the development of effective prevention
      such as vaccines.
    

Detailed description: 
      AMENDED: An 80 mcg dose of gp160 has been chosen for the booster because this dose has been
      shown to be safe and immunogenic in previous trials and allows comparison of the late boost
      in this protocol with the late boost in the protocol in which patients were primed with three
      doses of gp160. Original design: HIVAC-1e vaccine is a preparation of the envelope protein of
      HIV (the virus that causes AIDS). The protein is produced by genetic modification in vaccinia
      virus. The purpose of a vaccine is to produce an artificially increased immunity to a
      particular disease, in this case, AIDS. Since there is no known cure for AIDS, the control of
      this disease necessitates the development of effective prevention such as vaccines.

      AMENDED: Participants in the amended study will be given one injection in the deltoid muscle
      of gp160 vaccine. The injection of gp160 will be given 2 months after the first take with the
      HIVAC-1e vaccine. After each inoculation, volunteers will be observed for one hour. For four
      days after each inoculation, each participant will be interviewed daily to monitor side
      effects and asked to record their temperature and symptoms twice daily. It is anticipated
      that a cohort of approximately 20 HIVAC-1e recipients from the participating AIDS Vaccine
      Evaluation Units will agree to receive the booster immunizations of gp160, and that this
      number of patients will be adequate to determine the booster effect of gp160. Original
      design: Study patients receive two immunizations, one at the beginning of the study and a
      second one eight weeks later. These immunizations are administered by scarification on the
      arm, the same way that smallpox vaccines were given for several years. The patients are
      divided into two groups. The control group receives a derivative of the smallpox vaccine that
      is used to produce HIVAC-1e vaccine. The treatment group actually receives HIVAC-1e. Whether
      a patient receives the parent virus or the vaccine is determined randomly by computer, and
      neither the patient nor the physician knows who actually receives the vaccine. The group
      receiving the parent virus and the group receiving HIVAC-1e are then divided into three
      subgroups receiving different doses of HIVAC-1e, in order to test the effectiveness of
      different doses of HIVAC-1e. Following the first inoculation and the booster inoculation
      eight weeks later, patients have the vaccination site covered with a special waterproof
      bandage until the vaccination site has healed. Participants are counseled on how to avoid
      contact spread of the vaccine virus including hand washing, management of the bandage, and
      separation from persons at high risk for the complications of the virus infection. Patients
      are closely followed for the first four weeks following immunization and then followed for a
      minimum of one year. Women are included only if willing to provide continuing information on
      sexual practices and menstrual patterns, and furnish urine samples, as appropriate, for
      pregnancy testing on the day of/before vaccination and every other week throughout the 56th
      day after receipt of vaccine. At the Johns Hopkins site, patients are compensated depending
      on how far they have to travel as long as they commit to every-other-day visits for the first
      30 days. This is to change the bandage and check on healing. Interested patients should call
      collect for additional information about travel pay.
    

Intervention name(s): HIVAC-1e; gp160 Vaccine (MicroGeneSys)
Intervention type(s): Biological; Biological
Masking: Double
Primary purpose: Prevention
Keywords: Vaccines, Synthetic; Vaccinia Virus; Viral Envelope Proteins; Acquired Immunodeficiency Syndrome; AIDS Vaccines; HIV Seronegativity; HIV Preventive Vaccine