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.