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)

Inclusion Criteria

Subjects must have:

• Negative ELISA and Western blot for HIV-1 within 6 weeks prior to immunization.
• Normal history and physical exam.
• History of smallpox vaccination at least 5 years prior to study entry (Part I) OR no prior smallpox vaccination (Part II).
• Absolute CD4 count >= 400 cells/mm3.
• Normal urinalysis.

NOTE:

• No more than 10 percent of volunteers in both Parts I and II may be over 50 years of age.

Exclusion Criteria

Co-existing Condition:

Subjects with the following symptoms or conditions are excluded:

• Positive hepatitis B surface antigen.
• Medical or psychiatric condition (such as recent suicidal ideation or present psychosis) that precludes compliance.
• Occupational responsibilities that preclude compliance.
• Active syphilis. NOTE: Subjects with serology documented to be a false positive or due to a remote (> 6 months) treated infection are eligible.
• Active tuberculosis. NOTE: Subjects with a positive PPD and a normal chest x-ray showing no evidence of TB and not requiring isoniazid therapy are eligible.
• Eczema.
• Household contact with persons meeting any of the following criteria:
• pregnancy, less than 12 months of age, eczema, immunodeficiency disease, or use of immunosuppressive medications.

Subjects with the following prior conditions are excluded:

• History of immunodeficiency, chronic illness, autoimmune disease, or use of immunosuppressive medications.
• History of anaphylaxis or other serious adverse reactions to vaccines.
• Eczema within the past year.
• History of serious allergic reaction to any substance, requiring hospitalization or emergent medical care (e.g., Steven-Johnson syndrome, bronchospasm, or hypotension).
• Prior psychiatric condition (such as history of suicide attempts or past psychosis) that precludes compliance.
• History of cancer unless there has been surgical excision that is considered to have achieved cure.

Prior Medication:

Excluded:

• Prior HIV vaccines.
• Live attenuated vaccines within the past 60 days. NOTE: Medically indicated subunit or killed vaccines (e.g., influenza, pneumococcal) do not exclude but should be administered at least 2 weeks prior to HIV immunizations.
• Experimental agents within the past 30 days.

Prior Treatment:

Excluded:

• Receipt of blood products or immunoglobulins within the past 6 months. It is STRONGLY RECOMMENDED that any activity that might expose subject to HIV (unprotected sex or needle sharing) be avoided.

History of severe allergic reactions to study medication Currently pregnant or breastfeeding Recent participation in another clinical trial within the last 30 days Presence of uncontrolled medical conditions that could affect safety