OUTLINE OF PROTOCOL 007C

Subjects: Healthy adult volunteers without identifiable high-risk behavior for HIV-1 infection.

Schema:

Product Description: CHO cell-derived HIV-1 SF-2 rgp120 in combination with MF59 adjuvant emulsion [Chiron/BIOCINE]

Time Period: First volunteer entered on 11/16/92 and the last on 12/21/92; follow-up of 18 months.

Clinical Sites: Vanderbilt University, University of Rochester, University of Washington

Study Chair: Barney Graham, Vanderbilt University

INCLUSION CRITERIA

• Age: 18-60
• Sex: Male or Female [For females, negative pregnancy test at time of entry]
• Normal history and physical examination
• Normal complete blood count and differential defined as:
  • Hematocrit >34% for women; >38% for men
  • White count >3500 cells/mm³ with normal differential
  • Total lymphocyte count >800 cells/mm³
  • Platelets (120,000-550,000)
• Normal urinalysis
• Normal ALT (<1.5 x institutional upper normal limit) and creatinine (0.1-1.6 mg/dl)
• Negative ELISA for HIV
• Normal cell mediated immune responses using Merieux skin test

  NOTE: If the skin test for TB on the Merieux panel has any reactivity, a PPD skin test will be performed. Volunteers with a positive PPD and a normal chest X-ray showing no evidence of TB and not requiring INH therapy are eligible for enrollment.

• Availability for 18 months of follow-up

EXCLUSION CRITERIA

• Immunoglobulin or vaccines within 3 months of study
• History of immunodeficiency, chronic illness, autoimmune disease, or use of immunosuppressive medications
• Evidence of psychological or psychiatric problems that may lead to non-compliance with study requirements
• Subjects with identifiable high risk behavior for HIV infection as determined by screening questionnaire designed to identify risk factors for HIV infection; specific exclusions include:
  • Any history of IV (intravenous) drug use within the last one year
  • Syphilis, gonorrhea, or any other sexually transmitted diseases (including chlamydia or pelvic inflammatory disease) in the last 6 months
  • More than two sexual partners, or sexual contact with a high risk partner, in the preceding 6 months
• Use of experimental agents within 30 days prior to study
• Receipt of blood transfusions or cryoprecipitates within the past 3 months
• Positive syphilis serology (e.g., RPR)
• NOTE: If the serology is documented to be a false positive or due to a remote (>6 months) treated infection, the volunteer is eligible.
• Circulating Hepatitis B surface antigenemia
• History of anaphylaxis or other adverse reactions to vaccines
• Prior receipt of HIV vaccines

STUDY GOALS

• To evaluate the safety and immune response to 200 µg of the gp120 candidate vaccine in the MF59 emulsion without MTP-PE using a schedule similar to that in Part A of the original study (Protocol 007A).
• To evaluate the duration of immune response and its relationship to the dose of inoculation.
• Study extension: To measure safety and immunogenicity of an additional dose of rgp120 in MF59 emulsion in vaccinees in Protocols 007A, 007B and 007C. Specifically, which priming schedule (0, 1, and 6 months or 0, 1, 2, 3, 4 months) results in a better booster response at 1218 months.

REFERENCE

Graham BS, Keefer MC, McElrath MJ, Gorse GJ, Schwartz DH, Weinhold K, Matthews TJ, Esterlitz JR, Sinangil F, Fast PE, NIAID AIDS Vaccine Evaluation Group. Safety and immunogenicity of a candidate HIV-1 vaccine in healthy adults: recombinant glycoprotein (rgp) 120. A randomized, double-blind trial. Ann Intern Med. 1996;125:270-279.