OUTLINE OF PROTOCOL 008

Subjects: Healthy, HIV-1 uninfected adult volunteers without identifiable high-risk behavior for HIV-1 infection, who have a history of smallpox vaccination >5 years prior to enrollment.

Schema:

Product Description:

HIVAC-1e: vaccinia vector containing HIV-1 LAI rgp160 [Bristol Myers-Squibb/Oncogen]
CHO cell-derived HIV-1 SF-2 rgp120 in combination with MF59 adjuvant emulsion [Chiron/BIOCINE]
Yeast-derived HIV-1 SF-2 rgp120 (ENV 2-3) in combination with MF59 adjuvant emulsion [Chiron/BIOCINE]

Time Period: The first volunteer entered on 07/30/92 and the last on 01/26/93; follow-up of 18 months.

Clinical Sites: Johns Hopkins University, Saint Louis University, University of Rochester, University of Washington, Vanderbilt University

Study Chair: Lawrence Corey, University of Washington

INCLUSION CRITERIA

• History of smallpox vaccination >5 years prior to study enrollment
• Age: 18-60
• Sex: Male or nonpregnant females
• Normal history and physical examination
• Normal complete blood count and differential defined as:
  • Hematocrit >34% for women, >38% for men
  • WBC >4000/mm³ with normal differential
  • Total lymphocyte count >800 cells/mm³
  • Absolute CD4 count >500 cells/mm³
  • Platelet count between 120,000 and 550,000/mm³
• Normal urinalysis
• ALT <3X institutional upper normal limit
• Creatinine <1.6 mg/dl
• Negative HIV ELISA, Western Blot, and p24 antigen (PBMC HIV culture or HIV-specific PCR can be substituted for Western Blot and p24 antigen)
• Availability for 18 months of follow-up

EXCLUSION CRITERIA

• Identifiable high risk behavior for HIV infection as determined by screening questionnaire/interview
• Blood or blood product transfusion within the previous 6 months
• History of immunodeficiency, chronic illness, or use of immunosuppressive medications in subjects
• Lactating women
• Eczema within the past year
• Household contacts who are pregnant, <12 months of age, have eczema, or have immunodeficiency disease or use of immunosuppressive medications
• Prior receipt of an experimental HIV vaccine
• Immunoglobulin administration or use of experimental agent within 2 months of enrollment
• Hepatitis B surface antigenemia
• Medical or psychiatric condition or occupational responsibilities which preclude subject compliance with the protocol

STUDY GOALS

The primary objective of this study is to extend our current state of knowledge on the use of combinations of candidate AIDS vaccines directed against HIV-1 envelope glycoproteins. Specifically, it is planned to evaluate in volunteers who have been vaccinia-primed by smallpox vaccination at least five years prior to initiation of the study:

• If vaccination with a combination of two different types of AIDS vaccines; i.e., a vaccinia HIV-1 gp160 envelope gene recombinant vaccine (HIVAC-1e, Bristol-Myers Squibb/Oncogen) and a recombinant subunit HIV-1 gp120 vaccine (ENV 2-3 or Chiron rgp120, BIOCINE) formulated in a unique emulsion, MF59, elicits an enhanced immune response compared to vaccination with the Chiron rgp120 subunit vaccine alone.
• Whether there is a significant augmentation in the immune response following boosting with Chiron rgp120 if the volunteer has received two inoculations of the HIVAC-1e, rather than one, prior to the subunit boost.
• If boosting with the Chiron rgp120 vaccine which displays both linear and conformational epitopes of HIV-1 gp120 induces increased functional immunity (neutralizing antibodies) in CD4 binding blocking antibodies, syncytia-inhibiting antibodies, etc.) compared to boosting with ENV 2-3, which only displays linear epitopes of gp120.

The secondary objectives of this study are to examine the safety of the administration of either ENV 2-3 or Chiron rgp120 in combination with HIVAC-1e.