OUTLINE OF PROTOCOL 006

Subjects: Healthy, HIV-1 uninfected adult volunteers who are at low risk for HIV-1 infection.

Schema:

Product Description:

CHO cell-derived HIV-1 IIIB rgp120 in alum [Genentech]
CHO cell-derived HIV-1 MN rgp120 in alum [Genentech]

Time Period: First volunteer entered on 03/25/91 and the last was enrolled on 06/26/91; follow-up of 22 months, or 6 months after the final immunization for volunteers on the extended schedule.

Clinical Sites: Johns Hopkins University, Saint Louis University

Study Chair: Mary Lou Clements, Johns Hopkins University

INCLUSION CRITERIA

• Age: 18-60
• Sex: Male and female
• No prior history of clinically significant cardiac, pulmonary, hepatic, renal, neurologic or autoimmune disease and in good general health as determined by a medical history, physical examination, and the following tests:
• Hgb 11-16 g/dL
• HCT >35 for females; >39 for males
• Total WBC >4,000/mm³
• Total Lymphocytes >800/mm³
• T4 Lymphocytes >400/mm³
• Platelet: 120,000-500,000/mm³
• Creatinine <1.6 mg/dL
• ALT <1.1 x institutional normal limits
• VDRL negative
• HBsAg negative
• Urinalysis - normal
• Negative PPD (if PPD is positive, a chest x-ray must be negative and with no suggestion of active or old pulmonary tuberculosis for subject to participate in the study)
• HIV-1 PCR or viral culture negative (obtained within 1 month before primary immunization)
• Seronegative for HIV including:
  • HIV ELISA (Abbott) antibody negative and
  • HIV Western Blot negative for gp120, gp160, and gp41
• p24 antigen negative
• Negative serum pregnancy test in females - within 3 days prior to primary immunization (additional pregnancy tests also required 72 hours prior to second and third immunization)
• No other immunization within 4 weeks of study entry
• No febrile illness within 1 week of study entry
• The ability to sign a written informed consent form [must be obtained <28 days (screen visit)
• Available for at least 12 months of follow-up

EXCLUSION CRITERIA

Subjects with identifiable high risk behavior for HIV infection (as determined by a prestudy questionnaire designed to identify risk factors for HIV infection)

Pregnant or lactating women (Women of child-bearing potential must be using effective contraception, including IUD, oral, or barrier method, for at least 60 days prior to initial immunization and throughout the 12-month study period.)

Concomitant drug exclusion: corticosteroids or other known immunosuppressive drugs; any experimental agent

STUDY GOALS

• To evaluate the safety (clinical and immunologic) of rgp120/HIV-1 IIIB vaccine immunization in healthy HIV-1 seronegative adult subjects
• To compare the immune response to 100 µg rgp120/HIV-1 IIIB vaccine
• To determine whether rgp120/HIV-1 IIIB vaccine immunization causes a significant immune response as defined by one or more of the following:
  • Induction of neutralizing antibodies to the IIIB isolate of HIV-1
  • Induction of cross-neutralization antibodies to HIV-1 isolates other than IIIB
  • Induction of antibodies to the principal neutralizing determinant of rgp120/HIV-1 IIIB vaccine (V3 loop)
  • Induction of gp120 antigen specific lymphocytic proliferation
  • Induction of antibody-dependent cellular cytotoxicity in response to rgp120
• Protocol 006 rollover: To evaluate the safety (clinical and immunologic) of MN rgp120/HIV-1 and IIIB rgp120/HIV-1 vaccines in healthy HIV-1 seronegative adult subjects who have already received three immunizations of IIIB rgp120/HIV-1, according to the original Protocol 006. The magnitude and duration of immune responses will also be measured.
• Protocol 006 extension: To evaluate the safety and immunogenicity of two 300 µg doses of MN rgp120/HIV-1 given 1 month apart to volunteers previously immunized according to the original Protocol 006 and Protocol 006 rollover. The immune responses of volunteers in this study will be compared to that of volunteers in AVEG Protocol 009.
  

REFERENCE

Schwartz DH, Gorse G, Clements ML, Belshe R, Izu A, Duliege AM, Berman P, Twaddell T, Stablein D, Sposto R, Siliciano R, Matthews T. Induction of HIV-1-neutralising and syncytium-inhibiting antibodies in uninfected recipients of HIV-1 IIIB rgp120 subunit vaccine. Lancet. 1993;342:69-73.