Protocol 022A

OUTLINE OF PROTOCOL 022A

A PHASE I SAFETY AND IMMUNOGENICITY TRIAL OF LIVE RECOMBINANT CANARYPOX ALVAC-HIV (vCP205) AND HIV-1 SF-2 RGP120 IN HIV-1 UNINFECTED ADULTS

Subjects: Healthy, HIV-1 uninfected adult volunteers 18-60 years of age (no more than 10% will be older than 50 years of age), identified as belonging to one of two risk strata for HIV infection: 1) individuals without identifiable intermediate or higher-risk behavior or 2) homosexual males with intermediate or higher-risk behavior.

Schema:

		A: ALVAC-HIV vCP205 dose of 10^6.7 TCID₅₀S: SF-2 rgp120 (50 µg) in MF59
Group*	Total Volunteers	Low Risk	Higher Risk	Immunization Schedule in Months
Group*	Total Volunteers	Low Risk	Higher Risk	0	1	3	6	9	12
H	21/4	11/2	10/2	A	A	A	A	S	S
H	21/4	11/2	10/2	A	A	A	A	A	A
I	21/4	11/2	10/2	A	A	.	A	S	S
I	21/4	11/2	10/2	A	A	.	A	A	A
J	21/4	11/2	10/2	A	A	A+S	A+S	A+S	A+S
K	21/4	11/2	10/2	A	A	.	A+S	A+S	A+S
L	21/4	11/2	10/2	A+S	A+S	.	A+S	A+S	A+S
M	21/4	11/2	10/2	A+S	A+S	A+S	A+S	A+S	A+S
RX total	126/24	66/12	60/12	.
TOTAL	150	78	72	.

* Each Group includes 25 volunteers (21 treatment and 4 control volunteers). At each immunization, control volunteers will receive ALVAC-RG at a dose of 10^6.3 TCID₅₀ instead of ALVAC-HIV and/or MF59 (formulated as Placebo Vaccine 2) instead of SF-2 rgp120.

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 combined with MF59 adjuvant emulsion. [Chiron/BIOCINE]

Time Period: 24 months with the possibility of extension; first volunteer enrolled on 07/10/96 and the last on 05/05/97.

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

Study Chair: Lawrence Corey, University of Washington

INCLUSION CRITERIA

Standard inclusion criteria, with the addition of:

Negative Western Blot for HIV-1 (no envelope bands) within 8 weeks prior to immunization
For volunteers enrolled in the lower risk strata: Lower risk sexual behavior as defined by AVEG (i.e., meeting the criteria for AVEG Risk Group A or B)
For volunteers enrolled in the higher risk strata: Homosexual men having higher or intermediate risk sexual behavior as defined by AVEG (i.e., meeting criteria for AVEG Risk Group C or D)
An EBV transformed cell line known to be viable by day of enrollment or drawn at least 4 weeks prior to initial immunization

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 the safety and immunogenicity of high titered ALVAC-HIV (vCP205), 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. The vaccine is to be given to healthy, HIV-1 uninfected adult volunteers.

To evaluate the safety of a vaccine regimen of high titered ALVAC vCP205, along with HIV-1 SF-2 rgp120 in MF-59, given sequentially or simultaneously.
To evaluate the antibody and cellular responses to vCP205 recombinant vaccine alone or in combination with HIV-1 SF-2 rgp120 given sequentially or simultaneously.
To examine the immune response induced by two different schedules of immunization (0, 1, 3, 6, 9, and 12 months or 0, 1, 6, 9, and 12 months).
To examine the effect of HIV-1 SF-2 rgp120, as a boost or as part of the priming immunizations, on vCP205 responses.
To examine the effect of dose by comparing immune responses to high titered vCP205 and low titered vCP205 in some arms by determining:
- CD8+ and CD4+ CTL activity specific for HIV-1, specifically CTL to gag/protease and envelope, including the frequency and time course of the CTL response to vCP205
- T-helper response to HIV proteins using lymphocyte proliferation
- Neutralizing antibodies to HIV-1 MN and HIV-1 SF-2
- Cross-neutralizing antibodies to other isolates of HIV-1
- Antibodies that block binding of gp120 to CD4+ cells
- Antibody-dependent cellular cytotoxicity
- HIV-1 MN and HIV-1 SF-2 antigen specific binding antibodies
To evaluate whether differences exist in the CTL response between low risk individuals and higher risk homosexually active men in AVEG Risk Group C or D.