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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. 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.
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.