A Multicenter, Randomized, Placebo-Controlled, Double-Blind Trial to Evaluate the Safety and Immunogenicity of the Therion Recombinant Vaccinia-HIV-1 IIIB ENV/GAG/POL Vaccine (TCB-3B) and MN RGP 120/HIV-1 In Alum.

Study Overview
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Brief Summary
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To evaluate the safety of administering Therion Recombinant Vaccinia-HIV-1 IIIB env/gag/pol Vaccine (TBC-3B) vaccinations to vaccinia-naive individuals. To evaluate the immunogenicity of priming with TBC-3B by the scarification, intradermal, and subcutaneous routes, followed by booster immunization of MN rgp120 HIV-1. To compare the immunogenicity of priming with TBC-3B in vaccinia-naive individuals to vaccinia-immune individuals. In prior trials evaluating alternative methods of vaccine administration, scarification has been found to be an imprecise method of administration and allows only 1.0 - 2.5 microliters of immunogen to be given. Since it is not feasible to produce vaccine at concentrations higher than 10 to the 10th pfu/ml, this method limits the maximum deliverable dose. Intradermal and subcutaneous injection routes allow larger volumes of vaccinia to be given, i.e.: up to 200 microliters intradermally and up to 100 ml subcutaneously. In the present study, the initial priming dose will be the same administered by all 3 methods; however, the second priming dose administered at 2 months intradermally and subcutaneously will be 2 logs higher in order to achieve boosting of immune responses, particularly to gag and pol components of TBC-3B.

Detailed Description
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In prior trials evaluating alternative methods of vaccine administration, scarification has been found to be an imprecise method of administration and allows only 1.0 - 2.5 microliters of immunogen to be given. Since it is not feasible to produce vaccine at concentrations higher than 10 to the 10th pfu/ml, this method limits the maximum deliverable dose. Intradermal and subcutaneous injection routes allow larger volumes of vaccinia to be given, i.e.: up to 200 microliters intradermally and up to 100 ml subcutaneously. In the present study, the initial priming dose will be the same administered by all 3 methods; however, the second priming dose administered at 2 months intradermally and subcutaneously will be 2 logs higher in order to achieve boosting of immune responses, particularly to gag and pol components of TBC-3B. After volunteers are recruited, screened and enrolled in the study, they will be randomized to group C, D, or E. Each group will enroll 10 patients and 2 controls. The placebo control for TBC-3B will be standard vaccinia vaccination administered at doses no higher than that administered by scarification; the placebo control for MN rgp120 will be alum. Group C will receive undiluted TBC-3B by scarification, at months 0 and 2. Group D will receive diluted TBC-3B intradermally at month 0 and undiluted TBC-3B at month 2. Group E will receive diluted TBC-3B subcutaneously at month 0 and undiluted TBC-3B at month 2. At months 8 and 12 all groups will receive MN rgp 120/HIV-1 in alum intramuscularly.

Official Title
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A Multicenter, Randomized, Placebo-Controlled, Double-Blind Trial to Evaluate the Safety and Immunogenicity of the Therion Recombinant Vaccinia-HIV-1 IIIB ENV/GAG/POL Vaccine (TCB-3B) and MN RGP 120/HIV-1 In Alum.

Conditions
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HIV Infections

Intervention / Treatment
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* Biological: MN rgp120/HIV-1
* Biological: TBC-3B Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Patients must have: Negative FDA-approved ELISA for HIV within 8 weeks of immunization. Normal history and physical examination. Negativity for Hepatitis B surface antigen. Availability for follow-up for planned duration of the study (18 months). Exclusion Criteria Co-existing Condition: Patients with the following symptoms or conditions are excluded: Medical or psychiatric condition or occupational responsibilities that preclude subject compliance with the protocol. Specifically excluded are people with a history of suicide attempts, recent suicidal ideation or who have past or present psychosis. Active syphilis. NOTE: If the serology is documented to be a false positive or due to a remote (> 6 months) treated infection, the volunteer is eligible. Active tuberculosis. NOTE: Patients with a positive PPD and a normal chest X-ray showing no evidence of TB and not requiring INH therapy are eligible. Household contacts with, or occupational exposure to, people with any of the following: Pregnancy. <12 months of age. Eczema or Immunodeficiency disease. Use of immunosuppressive medications. Patients with the following prior conditions are excluded: History of immunodeficiency, chronic illness, malignancy or autoimmune disease. History of cancer, unless there has been surgical excision followed by a sufficient observation period to give a reasonable assurance of cure. Any history of anaphylaxis or history of other serious adverse reactions to vaccines. History of serious allergic reaction to any substance, requiring hospitalization or emergent medical care (e.g., Stevens-Johnson syndrome, bronchospasm, or hypotension). Eczema within the past year. History of smallpox vaccination. Envelope bands on HIV-1 Western blot within 8 weeks of immunization. Prior Medication: Excluded: Use of immunosuppressive. Live attenuated vaccines within 60 days of study. NOTE: Medically indicated subunit or killed vaccines (e.g. influenza, pneumococcal) do not exclude, but should be given at least 2 weeks prior to HIV immunizations. Experimental agents within 30 days prior to study. Prior receipt of HIV-1 vaccines or placebo recipient in a previous HIV vaccine trial. Receipt of blood products or immunoglobulin within past 6 months. Risk Behavior: Excluded: History of injection drug use within the last 12 months prior to enrollment. Higher or intermediate risk sexual behavior as defined by the AVEG. Lower risk sexual behavior as defined by AIDS Vaccine Evaluation Group (AVEG) procedures.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: MN rgp120/HIV-1|nan|
|Biological: TBC-3B Vaccine|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vaccines, Synthetic, Vaccinia Virus, Placebos, HIV-1, AIDS Vaccines, HIV Seronegativity, Genes, env, Genes, pol, Genes, gag, HIV Preventive Vaccine