Protocol 026

OUTLINE OF PROTOCOL 026

A PHASE I SAFETY AND IMMUNOGENICITY TRIAL OF LIVE RECOMBINANT CANARYPOX ALVAC-HIV (VCP300) AND HIV-1 SF-2 rgp120 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 = 140]

Schema:

	A: ALVAC-HIV vCP300 dose of 10^6.3 TCID₅₀SF: HIV-1 SF-2 rgp120 (50 µg) in MF59
		Immunization Schedule in Months
Group	Accrual	0	1	3	6	9
A	20	A	A	.	A	A
B	20	A	A	.	SF	SF
C	20	A	A	.	A+SF	A+SF
D	20	A	A	A	A	.
E	20	A	A	SF	SF	.
F	20	A	A	A+SF	A+SF	.
G	20	A+SF	A+SF	.	A+SF	A+SF

Note: Each group includes 17 treatment and 3 control volunteers. In each of the groups, control volunteers receive ALVAC-RG (vCP65) at a dose of 10^6.0 TCID₅₀ instead of ALVAC-HIV vCP300 and/or MF59 adjuvant emulsion (formulated as Placebo Vaccine 2) instead of HIV-1 SF-2 rgp120. The Protocol Team will evalute safety after the first 10 volunteers have received simultaneous administration of ALVAC vCP300 and SF-2 rgp120.

ACCRUAL, IMMUNIZATIONS AND FOLLOW-UP COMPLETED

Product Description:

ALVAC-HIV vCP300, 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 genes encoding the entire gag protein (LAI); a portion of the pol sequence sufficient to evoke protease (LAI); three additional pol CTL epitopes (LAI); and two CTL epitopes in the nef (LAI) gene. [Pasteur-Merieux/Connaught]
CHO cell-derived HIV SF-2 rgp120 antigen combined with MF59 adjuvant emulsion. [Chiron/BIOCINE]

Time Period: First volunteer enrolled on 02/06/96 and the last on 01/28/97; original follow-up of 24 months extended to 30 months

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

Study Co-Chairs: Thomas Evans and Michael Keefer, University of Rochester

INCLUSION CRITERIA

Standard inclusion criteria, with the addition of:

No envelope bands on Western Blot for HIV-1 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)
Previous immunization against rabies

STUDY GOALS

To evaluate the safety and immunogenicity of ALVAC-MN120TMGNP (vCP300).
To also evaluate the effect of boosting of this vaccine with a recombinant gp120 product when given in both a simultaneous and sequential fashion.
To evaluate the antibody and cellular immune responses to vCP300 recombinant vaccine followed by or combined with a subunit boost 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, pol, nef and env, including the frequency and time course of CTL response to vCP300;
- 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 and/or IgG in parotid saliva and genital secretions specific for HIV.

REFERENCE

Evans TG, Keefer MC, Weinhold KJ, Wolff M, Montefiori D, Gorse GJ, Graham BS, McElrath MJ, Clements-Mann ML, Mulligan MJ, Fast P, Walker MC, Excler JL, Duliege AM, Tartaglia J, NIAID AIDS Vaccine Evaluation Group. A canarypox vaccine expressing multiple human immunodeficiency virus type 1 genes given alone or with rgp120 elicits broad and durable CD8+ cytotoxic T lymphocyte responses in seronegative volunteers. J Infect Dis.1999;180:290-298.