A Phase I, Multicenter, Randomized Trial to Evaluate the Safety and Immunogenicity of a Recombinant Vaccinia-HIV Envelope Vaccine (HIVAC-1e) in Combination With a Panel of Subunit Recombinant HIV Envelope Vaccines in Vaccinia-Naive Individuals

Previous studies suggest that priming with an HIV-vaccinia recombinant followed by boosting with subunit envelope proteins offers the most promising strategy to date for a safe and immunogenic vaccine in humans. This study will further examine the combination vaccine approach and define an optimal prime-boost strategy.

Healthy volunteers are randomized to one of eight groups. All patients receive initial immunization with HIVAC-1e, followed by two boosts at months 8 and 12 of rgp120/HIV-1SF2 (BIOCINE), rgp120/HIV-1IIIB (Genentech), rgp120/HIV-1MN (Genentech), or gp160 MN (Immuno-AG). Additionally, half of the patients in each subunit vaccine group receive a repriming with HIVAC-1e at month 4. Subjects are followed for 18 months.

Inclusion criteria

Subjects must have:

• Normal history and physical exam.
• Negative HIV screening by ELISA, Western blot, and p24 antigen (PBMC HIV culture or HIV-specific PCR can be substituted for Western blot and p24 antigen).
• No history of smallpox (vaccinia) vaccination.
• Normal urinalysis.
• Absolute CD4 count = or > 500 cells/mm3.

Exclusion criteria

Co-existing Condition:

Subjects with the following conditions are excluded:

• Hepatitis B surface antigenemia.
• Medical or psychiatric condition that precludes compliance with the protocol.

Subjects with the following prior conditions are excluded:

• History of immunodeficiency or chronic illness.
• Eczema within the past year.

Prior Medication:

Excluded:

• Prior experimental HIV vaccine.
• Prior smallpox vaccine.
• Immunoglobulin administration within 2 months prior to enrollment.
• Any experimental agent within 2 months prior to enrollment.
• History of use of immunosuppressive medications.

Prior Treatment:

Excluded:

• Blood or blood product transfusion within the past 6 months.

• Current high risk for HIV transmission (persons previously at high risk for HIV transmission can be enrolled provided they have a negative HIV screening and no high-risk behavior has been practiced within the last 6 months).
• Household contact with anyone who is pregnant, has eczema, is less than 12 months of age, or has immunodeficiency disease or is using immunosuppressive medications.