OUTLINE OF PROTOCOL 009

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

Schema:

Product Description:

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

Time Period: First volunteer entered the original study on 03/20/92 and the last entered on 07/07/92. The extension was activated in December 1993. Total follow-up of 15 months for those not participating in the extension, and approximately 32 months for those participating in the extension.

Clinical Sites: Saint Louis University, University of Rochester, Vanderbilt University

Study Chair: Robert Belshe, Saint Louis University

INCLUSION CRITERIA

• Age: 18-60
• Sex: Male and female
• No current or past history of clinically significant cardiac, pulmonary, neoplastic, hepatic, renal, neurologic or autoimmune disease
• Hgb: 12-18 g/dL
• Total WBC >4,000/mm³
• Platelet: 120,000-500,000/mm³
• Creatinine <1.2 mg/dL
• ALT <1.5 x institutional normal limits
• VDRL negative
• Urinalysis: no significant abnormality
• PPD (Purified Protein Derivative) should be negative. If PPD is positive, subject must have a clear chest x-ray with no suggestion of active or old pulmonary tuberculosis, and not be eligible for tuberculosis prophylaxis, such as isoniazid (INH).
• Hepatitis B or C Status: No serologic evidence of past or present Hepatitis C infection and no present or recent (within 2 years) evidence of Hepatitis B infection. Subjects who are HbsAb positive are eligible for the study if positivity is the result of a Hepatitis vaccination OR the infection occurred greater than 2 years prior to the screening visit based on the subject's history, and the following criteria are fulfilled: no evidence of elevated liver enzymes in the past 2 years, HBsAg negative, HBeAg negative, and HBcAb negative
• Documentation of negative results to the following HIV-1 tests: HIV ELISA (Abbott), HIV Western Blot (bands gp41, gp120, and gp160 must be negative for entry), and negative HIV-1 culture results
• Negative urine pregnancy test (females) obtained at screening and at the day of each immunization
• No other immunization within 4 weeks of study entry
• No febrile illness within 1 week of study entry
• Ability to sign a written informed consent form; must be obtained at <28 days (screen visit)
• Available for 15 months after the first injection so that follow-up may be completed

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 for at least 60 days prior to initial immunization; subjects using birth control must agree to do so for the entire study period
• Concomitant drug exclusion: corticosteroids or other known immunosuppressive drugs; any experimental agent; any anti-tuberculous medication, e.g., isoniazid (INH)
• Personnel engaged in the blinding of this study
• Subjects who for any reason cannot adhere to the schedule of this protocol should not be enrolled in the study
• Any prior history of receiving an HIV vaccine

STUDY GOALS

• To evaluate the clinical and immunologic safety of MN rgp120/HIV-1 vaccine given alone or concurrently with the 111B rgp120/HIV-1 in healthy HIV-1 seronegative adult subjects.
• To compare the immune response to MN rgp120/HIV-1 given at either 100 µg of MN rgp120/HIV-1 and IIIB rgp120/HIV-1 given concurrently.
• Protocol 009 extension: To evaluate the influence of prior immunization with an rgp120 vaccine on immune responses to a subsequent immunization with a different strain of rgp120. To evaluate and compare the magnitude, breadth and duration of the humoral immune responses to HIV-1 induced by immunization with rgp120 vaccines based on HIV-1 IIIB or HIV-1 MN, when given alone, in sequence or in combination.

REFERENCE

Belshe RB, Graham BS, Keefer MC, Gorse GJ, Wright P, Dolin R, Matthews T, Weinhold K, Bolognesi DP, Sposto R, Stablein DM, Twadell T, Berman PW, Gregory T, Izu AE, Walker MC, Fast P (NIAID AIDS Vaccine Clinical Trials Network). Neutralizing antibodies to HIV-1 in seronegative volunteers immunized with recombinant gp120 from the MN strain of HIV-1. JAMA. 1994;272:475-480.