Protocol 029

OUTLINE OF PROTOCOL 029

A PHASE I SAFETY AND IMMUNOGENICITY TRIAL OF LIVE RECOMBINANT CANARYPOX ALVAC-HIV (VCP205) AND HIV-1 SF-2 RGP120 ADMINISTERED IN AN ACCELERATED SCHEDULE

Subjects: Healthy, HIV-1 uninfected adult volunteers 18-60 years of age (no more than 10% will be older than 50 years of age), without identifiable intermediate or higher-risk behavior for HIV-1 infection. [Number of Subjects = 34]

Schema:

Group	Accrual*	Immunization Schedule in Days
Group	Accrual*	0	7	14	21	28	84
A	22	A	A	A	A	S	S
B	6	R	R	R	R	S	S
C	6	R	R	R	R	MF	MF
A: vCP205 dose of 10^6.7TCID₅₀S: HIV-1 SF-2 rgp120 in MF59 adjuvant R: ALVAC-RG (vDP65) dose of 10^6.0 TCID50 MF: MF59 adjuvant emulsion (formulated as Placebo Vaccine 2) * Total of 35 volunteers enrolled.

ACCRUAL, IMMUNIZATIONS AND FOLLOW-UP COMPLETED

Product Description:

ALVAC-HIV vCP205 is a recombinant canarypox vector 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]
CHO cell-derived HIV-1 SF-2 rgp120 in combination with MF59 adjuvant. [Chiron/BIOCINE]

Time Period: 12 months with the possibility of extension; first volunteer enrolled on 07/31/96 and the last on 12/06/96.

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

Study Chair: Robert Belshe, Saint Louis University

INCLUSION CRITERIA

Standard inclusion criteria, with the addition of

Negative Western Blot for HIV-1 (no envelope bands) within 8 weeks prior to immunization
An EBV transformed cell line known to be viable by day of enrollment

EXCLUSION CRITERIA

Standard exclusion criteria, with the addition of

Allergy to egg products or neomycin (used to prepare ALVAC vaccines)
Occupational exposure to birds
Previous immunization against rabies

STUDY GOALS

To evaluate an accelerated immunization schedule of ALVAC-HIV (vCP205) priming and HIV-1 SF-2 rgp120 boosting for safety and immunogenicity. The following genes have been inserted into ALVAC-HIV vCP205: 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. The vaccine is to be given to healthy, HIV-1 uninfected adult volunteers, followed by boosting with HIV-1 SF-2 rgp120 in MF-59.
To evaluate the safety of an accelerated schedule of priming with ALVAC vCP205 and boosting with SF-2 rgp120 in MF-59.
To evaluate the antibody and cellular immune responses to vCP205 recombinant vaccine after rapid vaccination schedules, followed by SF-2 rgp120 by determining whether immunization induces one or more of the following:
- CD8+ and CD4+ cytotoxic T lymphocyte (CTL) activity specific for HIV-1, specifically CTL to gag/protease and envelope, including the frequency as compared to that in AVEG Protocols 012, 022 and 026 and the kinetics of CD8 + CTL development after 2, 3 or 4 doses of vCP205.
- Neutralizing antibodies to HIV-1 MN after two doses of SF-2 rgp120 following vCP205 priming
- Cross-neutralizing antibodies to other isolates of HIV-1