Protocol 022

OUTLINE OF PROTOCOL 022

A PHASE I SAFETY AND IMMUNOGENICITY TRIAL OF LIVE RECOMBINANT CANARYPOX ALVAC-HIV (vCP205) IN HIV-1 UNINFECTED ADULT VOLUNTEERS

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. [Number of Subjects = 76 (NOTE: Accrual closed at 75 volunteers); 50% never vaccinated with vaccinia virus (vaccinia-naive)].

Schema:

A: ALVAC-HIV (vCP205) dose of 10^5.8 TCID₅₀RG: ALVAC-RG (vCP65) dose of 10^6.3 TCID₅₀SF: SF-2 rgp120 (50 µg) in MF59

MF59: MF59 adjuvant emulsion

		Immunization Schedule in Months
Group	Accrual	0	1	2	3	5	6	*9	*12
A1	12	A	A		A		A	SF	SF
A2	12	A	A		A		A	A+SF	A+SF
B1	3	RG	RG		RG		RG	MF59	MF59
B2	3	RG	RG		RG		RG	RG+MF59	RG+MF59
C1	12	A	A				A	SF	SF
C2	12	A	A				A	A+SF	A+SF
D1	3	RG	RG				RG	MF59	MF59
D2	3	RG	RG				RG	RG+MF59	RG+MF59
E	8	RG	RG	A	A	A
F	4	RG	RG	RG	RG	RG
G	4	A	A	RG	RG	RG

* Study extension

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 gp120 antigen combined with MF59 adjuvant emulsion. [Chiron/BIOCINE]

Time Period: First volunteer enrolled on 05/11/95 and the last on 11/16/95; protocol follow-up extended to 24 months, with one more visit at 30-36 months for additional cellular assays.

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 or p24 bands) within 8 weeks prior to 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 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.

To evaluate the antibody and cellular immune responses to vCP205 recombinant vaccine 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 and time course of CTL response to vCP205;
HIV-1 antigen-specific lymphoproliferation (indicative of immunological memory);
neutralizing antibodies to HIV-1 MN;
cross-neutralizing antibodies to other isolates of HIV-1;
antibodies that block binding of gp120 to CD4+ cells;
antibody-dependent cellular cytotoxicity;
DTH (delayed type hypersensitivity) response to HIV-1 MN after vaccination;
Secretory IgA specific for HIV in parotid saliva after vaccination.

Study extension:

To compare the immune response induced by two different schedules (0, 1, 3, 6, 9 and 12 months or 0, 1, 6, 9 and 12 months).
To evaluate the immunogenicity of ALVAC- HIV (vCP205) with and without prior administration of ALVAC-RG; to assess if repeated doses of canarypox vector influence the subsequent immune response.