Protocol 012B

OUTLINE OF PROTOCOL 012B

A PHASE I SAFETY AND IMMUNOGENICITY TRIAL OF LIVE RECOMBINANT CANARYPOX-GP160 MN (ALVAC VCP125, HIV-1 GP160 MN) IN HIV-1 UNINFECTED ADULTS

Subjects: Healthy, HIV-1 uninfected adult volunteers 1860 years of age (no more than 10% will be older than 50 years of age), who have no identifiable high-risk behavior for HIV-1 infection.

Schema:

Treatment (T1): ALVAC vCP125 HIV-1 gp160 MN dose of 10⁷ TCID₅₀Control (ARG): ALVAC vCP65 rabies glycoprotein 10^5.5 TCID₅₀rgp120 (T2): SF-2 rgp120 (50 µg) in MF59 (BIOCINE)
Group	Vaccinia Status	Accrual***	Immunization Schedule in Months
			0	1	2	6	9 (N)	12 (N)
E	Immune	20*	T1	T1			T1 (10)	T1 (10)
							T2 (10)	T2 (10)
F	Immune	20*	T1		T1		T1 (10)	T1 (10)
							T2 (10)	T2 (10)
G	Immune	10**	ARG	ARG			ARG (4)	ARG (4)
							T2 (6)	T2 (6)
H	Immune	10**	ARG		ARG		ARG (4)	ARG (4)
							T2 (6)	T2 (6)
I	Naive	20*	T1		T1		T1 (10)	T1 (10)
							T2 (10)	T2 (10)
J	Naive	10**	ARG		ARG		ARG (4)	ARG (4)
							T2 (6)	T2 (6)
K	Either	10	T2	T2		T2		T2

* 50% of subjects randomly assigned to receive SF-2 rgp120 (50 µg) in MF59 (BIOCINE) subunit boost at Months 9 and 12; the other 50% to receive ALVAC rgp160 MN
** Six subjects to receive SF-2 rgp120 (50 µg) in MF59 (BIOCINE) subunit boost at Months 9 and 12; the other four to receive ARG
*** Total of 101 volunteers enrolled.

ACCRUAL, IMMUNIZATIONS, AND FOLLOW-UP COMPLETED

Product Description:

ALVAC-HIV vCP125: live, recombinant canarypox-HIV-1 MN gp160 [Pasteur Merieux/Connaught]
CHO cell-derived HIV-1 SF-2 rgp120 in combination with MF59 adjuvant emulsion [Chiron/BIOCINE]

Time Period: First volunteer enrolled on 10/13/93 and the last on 06/22/94; follow-up of 18 months

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

Study Chair: Mary Lou Clements-Mann, Johns Hopkins University

INCLUSION CRITERIA

Standard AVEG inclusion criteria.

EXCLUSION CRITERIA

Standard AVEG exclusion criteria with the addition of:

Persons with an allergy to egg products or neomycin.
Persons with an occupational exposure to birds.
Previous immunization against rabies.

STUDY GOALS

To evaluate the safety and immunogenicity of ALVAC-HIV (vCP125) gp160 MN live canarypox recombinant vaccine (hereafter referred to as ALVAC gp160 MN) in healthy, HIV-1 uninfected adult volunteers.
To evaluate the cellular and humoral immune responses resulting from priming and boosting with 10⁶ or 10⁷ TCID₅₀ of ALVAC gp160 MN recombinant vaccine by determining whether immunization induces immune response as defined by one or more of the following:
- Neutralizing antibodies to the MN isolate of HIV-1;
- Cross-neutralizing antibodies to other isolates of HIV-1;
- Antibodies that block binding of gp120 to CD4 positive cells;
- Antibody dependent cellular cytotoxicity;
- Gp160 antigen-specific lymphoproliferation (indicative of immunological memory); and
- CD8+ and CD4+ cytotoxic T lymphocyte (CTL) activity specific for gp160 of MN and other HIV-1 strains;
- DTH (delayed type hypersensitivity) response to HIV-1 MN and IIIB envelope proteins, if available by IND approval and/or agreement with other manufacturers.
To compare the immune response induced by a dose of 10⁶ TCID₅₀ of ALVAC gp160 in vaccinia-naive with that induced in vaccinia-immune individuals.
To compare the immune response induced by two different schedules (0 and 2 months or 0 and 1 months) of a higher dose of 10⁷ TCID₅₀ ALVAC gp160 MN vaccine.
To compare the safety and immunogenicity of ALVAC gp160 MN to that of ALVAC vCP65 rabies glycoprotein
To determine whether ALVAC priming, followed by boosting with SF-2 rgp120, generates humoral and cellular immune responses.

REFERENCE

Clements-Mann ML, Weinhold K, Matthews TJ, Graham BS, Gorse GJ, Keefer MC, McElrath MJ, Hsieh RH, Mestecky J, Zolla-Pazner S, Mascola J, Schwartz D, Siliciano R, Corey L, Wright PF, Belshe R, Dolin R, Jackson S, Xu S, Fast P, Walker MC, Stablein D, Excler JL, Tartaglia J, Duliege AM, Sinangil F, Paoletti E, NIAID AIDS Vaccine Evaluation Group. Immune responses to human immunodeficiency virus (HIV) type 1 induced by canarypox expressing HIV-1MN gp120, HIV-1SF2 recombinant gp120, or both vaccines in seronegative adults. J Infect Dis. 1998;177:1230-1246.