OUTLINE OF PROTOCOL 032

Subjects: Healthy, HIV-1 uninfected volunteers aged 18-60 with lower risk of HIV-1 infection.

Schema:

Group	Number	IMMUNIZATION SCHEDULE IN MONTHS
		0	1	3	6
1	16	A+P	A+P	A+P	A+P
2	16	A+M	A+M	A+P	A+P
3	16	A+M	A+M	A+PS	A+PS
4	8	A+M	A+M	A+S	A+S
5	8	R+M	R+M	R+M	R+M
Total	64	A: ALVAC-HIV vCP205, 106.6TCID50 [Pasteur Merieux Connaught], administered IM (left arm) P: HIV-1 SF-2 p24 (50 µg) in MF59 [Chiron Vaccines], administered IM (right arm) S: HIV-1 SF-2 rgp120 (50 µg) in MF59 [Chiron Vaccines], administered IM (right arm) PS: HIV-1 SF-2 p24 (50 µg) combined with HIV-1 SF-2 gp120 (50 µg) in MF59 [Chiron Vaccines], administered IM (right arm) M: MF59 adjuvant + citrate vehicle [Chiron Vaccines] will be the control for p24 and SF-2 rgp120; administered IM (right arm) R: ALVAC-RG [Pasteur Merieux Connaught] will be the control for ALVAC-HIV vCP205, administered IM (left arm)

Note: Volunteers receive an injection in both arms at each of the four immunizations.  

Product Description: Recombinant subunit p24 antigen is derived from the SF-2 p24 isolate of HIV-1 and is expressed in genetically engineered Saccharomyces cerevisiae organisms and formulated in combination with MF59 adjuvant emulsion. [Chiron Vaccines].

CHO cell-derived SF-2 rgp120 in combination with MF59 adjuvant emulsion. [Chiron Vaccines]

ALVAC-HIV vCP205 is a recombinant canarypox vector vaccine into which the following genes have been inserted: HIV-1 envelope gp120 (strain MN) linked to the transmembrane portion of HIV-1 gp41 (strain LAI) and the HIV-1 LAI genes encoding the entire gag protein and a portion of the pol sequence, sufficient to evoke the protease portion. [Pasteur Merieux Connaught]

Time Period: 18 months; first volunteer enrolled 08/05/99 and the last on 09/29/99.

Clinical Sites: University of Alabama at Birmingham, Johns Hopkins University, Saint Louis University, Vanderbilt University, University of Rochester, and University of Washington

Study Chair: Mark Mulligan, University of Alabama at Birmingham

INCLUSION CRITERIA

Standard inclusion criteria

EXCLUSION CRITERIA

Standard exclusion criteria, with the addition of:

• Immediate-type hypersensitivity reaction to egg product or neomycin (used to prepare ALVAC vaccines)
• Previous immunization against rabies

STUDY GOALS

• This controlled, randomized Phase I trial in HIV-negative adults will evaluate the safety and immunogenicity of the HIV-1 SF-2 recombinant p24 subunit vaccine when administered as part of "prime-boost" HIV-1 vaccination regimens employing ALVAC-HIV vCP205 with or without HIV-1 SF-2 rgp120.

TRIAL ENDPOINTS

• Primary: The safety and tolerability of HIV-1 SF-2 p24 when administered simultaneously with ALVAC-HIV vCP205 (Groups 1 and 2), or when combined with HIV-1 SF-2 rgp120 administered simultaneously with ALVAC HIV-1 vCP205 (Group 3).
• Secondary: Immunogenicity endpoints as follows:
  • T cell responses (CD8+ or CD4+) to gag or other HIV-1 proteins induced by the prime-boost regimens utilizing HIV-1 SF-2 p24 vaccine (arms 1, 2 and 3) relative to "standard" prime-boost regimens (arm 4 or historical experience) or to canary-pox alone (historical experience)
  • Antibodies to gag antigens as detected on clinical ELISA or Western blot assays relative to historical experience. Note: Because of the relatively small arm sizes, analyses of gag-specific antibody or T cell responses will be performed for all p24 containing arms combined (n=48) as well as for each individual arm (n=16).
• Tertiary:
  • HIV-1 neutralizing antibodies (NAB) to confirm that addition of HIV-1 SF-2 p24 to prime-boost regimen doesn't reduce NAB.