OUTLINE OF PROTOCOL 005B

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

Schema:

Product Description: Yeast-derived HIV-1 SF-2 rgp120 (ENV 2-3) in combination with MF59 adjuvant emulsion ± MTP-PE (muramyl tripeptide-phosphatidylethanolamine) adjuvant [Chiron/BIOCINE]

Time Period: First volunteer entered on 03/25/91 and last enrolled on 10/16/91; follow-up of 6 months after the last injection.

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

Study Chair: Raphael Dolin, University of Rochester

INCLUSION CRITERIA

• Age: >18 and <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 >500 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
• Subject who has a p24 band present on Western Blot may be enrolled if HIV culture or PCR are negative, and after 3 months there are no additional bands or increased intensity of the p24 band [criterion modified 4/91]
• Negative HIV p24 antigen test
• Normal cell mediated immune responses using Merieux skin test
• Negative HIV culture
• Availability for one year of follow-up

EXCLUSION CRITERIA

• History of immunodeficiency, chronic illness, autoimmune disease, or use of immunosuppressive medications
• Evidence of depression or under treatment for psychiatric problems during the past year
• 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
  • 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
• Previous receipt of blood transfusions or cryoprecipitates within the past 6 months
• Subject may be enrolled if the positive syphilis serology (e.g., VDRL) test is due to a documented clinical event that occurred and was treated 5 years prior to enrollment [criterion modified 4/91]
• Circulating Hepatitis B antigenemia

STUDY GOALS

This is a Phase I study whose purpose is to determine the safety and immunogenicity of ENV 2-3 in combination with MTP-PE/MF59 in volunteers. Specific questions to be addressed include:

• Are there adverse clinical reactions or laboratory evidence of toxicities associated with administration of the adjuvant or combined vaccine and adjuvant?
• Does the candidate HIV vaccine preparation (ENV 2-3/MTP-PE/MF59) generate anti-HIV humoral antibody responses in healthy volunteers?
• Does the HIV candidate vaccine (ENV 2-3/MTP-PE/MF59) stimulate cell-mediated immune responses against HIV?

REFERENCE

Keefer MC, Graham BS, McElrath MJ, Matthews TJ, Stablein DM, Corey L, Wright PF, Lawrence D, Fast PE, Weinhold K, Hsieh RH, Chernoff D, Dekker C, Dolin R, NIAID AIDS Vaccine Evaluation Group. Safety and immunogenicity of env 2-3, a human immunodeficiency virus type 1 candidate vaccine, in combination with a novel adjuvant, MTP-PE/MF59. AIDS Res Hum Retroviruses. 1996;12:683-693.