Protocol 020

OUTLINE OF PROTOCOL 020

A PHASE I SAFETY AND IMMUNOGENICITY TRIAL OF HIV-1 GP120 C4-V3 HYBRID POLYVALENT PEPTIDE IMMUNOGEN MIXED IN MINERAL OIL CONTAINING MANNOSE MONO-OLEATE (IFA)

Subjects: Healthy, HIV-uninfected adult volunteers with lower risk for HIV-1 infection; 50% must have the HLA-B7 phenotype. [Total planned = 28 volunteers]***

Schema:

Immunizations originally scheduled at Days 0, 28, 182, and 364***
Group	C4-V3 Peptides In IFA	IFA Alone
I	*12 (1 mg total, 250 µg of each peptide)
II	*12 (4 mg total, 1 mg of each peptide)
III		4**
Total	24***	4***

* 6 subjects will be HLA-B7 phenotype
** 2 subjects will be HLA-B7 phenotype
*** Enrollment suspended at total of 24; Day 182 and 364 immunizations canceled

ACCRUAL, IMMUNIZATIONS AND FOLLOW-UP COMPLETED

Product Description: HIV-1 gp120 C4-V3 hybrid polyvalent peptide immunogen in mineral oil + mannose mono-oleate (IFA). Four synthetic peptides based on the HIV-1 clade B strains MN, EV91, RF and CANO are included in the candidate vaccine. [Wyeth-Lederle Vaccines and Pediatrics]

Time Period: 18 months originally--shortened to 12.5 months; first volunteer enrolled on 10/22/97 and the last on 03/05/98. Accrual and immunizations stopped 03/10/98 for safety reasons.

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

Study Chair: Barney Graham, Vanderbilt University

INCLUSION CRITERIA

Standard inclusion criteria, with the addition of:

14 subjects (6 each in Groups I and II, 2 in Group III) will be HLA class I MHC haplotype B7
Normal GGT (<1.5 x institutional upper normal limit)
Normal chest x-ray within 4 weeks prior to initial immunization
Agree to limit alcohol intake during study participation to less than the equivalent of 1 oz of 100 proof per day (4 oz glass of wine or 12 oz glass of beer per day)

EXCLUSION CRITERIA

Standard exclusion criteria, with the addition of:

History of lung disease

STUDY GOALS

The primary objective is to evaluate the safety of the C4-V3 peptides in IFA in HIV-1 uninfected volunteers.

The secondary objective is to evaluate the humoral and cellular immune responses to the C4-V3 peptides by determining whether immunization induces one or more of the following:

Neutralizing antibodies to HIV-1 MN and RF
Cross neutralizing antibodies to primary isolates of HIV-1
HIV-1 antigen -specific lymphoproliferation
CD8 + and CD4 + cytotoxic T lymphocyte (CTL) activity specific for HIV-1 gp120 or V3 peptides corresponding to the vaccine strains of HIV-1
Induction of HLA-B7 and HLA-A2 restricted CD8 + CTLs
Induction of HIV-specific DTH responses