OUTLINE OF PROTOCOL 007B

Subjects: Healthy, HIV-1 uninfected adult female 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 02/05/92 and the last entered on 04/14/92; follow-up extended to 6 months after final immunization.

Clinical Sites: Johns Hopkins University, Saint Louis University

Study Chair: Barney Graham, Vanderbilt University

INCLUSION CRITERIA

• Age: 18-50
• Sex: Male or Female [NOTE: For females, negative pregnancy test at time of entry.]
• Normal history and physical examination
• Normal complete blood count and differential defined as:
  • Hematocrit >35% for women; >39% for men
  • White count >4000 cells/mm³ with normal differential
  • Total lymphocyte count >800 cells/mm³
  • Platelets (120,000-550,000)
• Normal urinalysis
• Normal ALT (<1.1 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
• Availability for one year of follow-up

EXCLUSION CRITERIA

• Immunoglobulin or vaccines within 2 months of study
• History of immunodeficiency, chronic illness, autoimmune disease, or use of immunosuppressive medications
• Significant evidence of depression or under treatment for psychiatric problems during the past year as determined by the Principal Investigator
• 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) that is documented not to be a false positive or from a remote (>6 months) treated infection
• Circulating Hepatitis B antigenemia
• History of anaphylaxis or other adverse vaccine reactions

STUDY GOALS

The goal of this Phase I study is to compare the safety and immunogenicity of two dose levels of gp120 (CHO) in the MF59 emulsion alone or with MTP-PE in MF59 adjuvant, given at 0, 1 and 6 months. Specific questions to be addressed include:

• Are there adverse clinical reactions or laboratory evidence of toxicities associated with administration of the gp120 with MF59 emulsion alone or with MTP in MF59 adjuvant?
• Does the candidate HIV vaccine preparation (gp120 [CHO]/MF59/MTP-PE) generate HIV-specific antibody responses in healthy seronegative volunteers? If so, does the antibody have functional activity, such as in vitro neutralization?
• Does the HIV candidate vaccine (gp120 [CHO]/MF59/MTP-PE) stimulate cell-mediated immune responses against HIV in healthy seronegative volunteers?
• Does increasing the dose of antigen protein from 15 µg to 50 µg significantly alter either safety or immunogenicity?
• Does the inclusion of MTP-PE significantly alter either safety or immunogenicity of the vaccine product?
• Can an intensified, compressed schedule of immunizations with the gp120 in MF59 emulsion alone improve the immune responses to gp120 (CHO) without altering adverse reactions?

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, (1) which priming schedule (0, 1, and 6 months or 0, 1, 2, 3, 4 months) results in a better booster response at 1218 months and (2) whether a rest period restores the capacity for boosting in Protocol 007B vaccinees.

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.