OUTLINE OF PROTOCOL 027

Subjects: Healthy, HIV-1 uninfected adult volunteers 18-50 years of age who have lower risk behavior for HIV-1 infection. [Number of Subjects = 84]

Schema: Modified to include two booster vaccinations to be administered at Month 9 (or greater) and 6 months later.

2 booster vaccinations to be administered at 9^# and 15^# months

Group	Number**	Months 0, 1, 3, 6		Months 9, 15#
		Product	Route of Administration	Product	Route of Administration
A	12	A or RG	IM	A or RG	IN
B	12	A or RG	PO	MN or IVX	IM
C	12	A or RG	IN	MN or IVX	IM
D	12	A or RG	IR	MN or IVX	IM
E	12	A or RG	IVag	MN or IVX	IM
F	12	A or RG	IN/IM	MN or IVX	IM
G	12	A or RG	IR/IM	MN or IVX	IM
Products:		A: ALVAC-HIV (vCP205) dose of 106.7 TCID50 dose if 106.75 for months 9 and 15# RG: ALVAC-RG (vCP65) dose of 106.3 TCID50 dose if 106.24 for months 9 and 15# MN: VaxGen MN rgp120 at a dose of 300 mcg/mL in 0.6 mg alum adjuvant IVX: Imovax diploid cell rabies vaccine
Routes of Administration:		IM: intramuscular PO: oral IN: intranasal IR: intrarectal IVag: intravaginal

** Each group will include 8 treatment and 4 control volunteers. In each of the groups, control volunteers will receive ALVAC-RG instead of ALVAC-vCP205 and Imovax instead of MN rgp120.
^# The first of the additional immunizations will be administered at Month 9; for volunteers who have passed the 9 month time point, the immunization will be administered as soon as possible after appropriate review and approval of this ammendment. The second of the booster immunizations will be administered 6 months later (Study Month 15, for those volunteers who received the first booster at Study Month 9).

 

ACCRUAL AND IMMUNIZATIONS 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 MN rgp120 in alum [VaxGen]

Time Period: 24 months with the possibility of extension; first volunteer enrolled on 11/03/97 and the last on 10/05/98.

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

Study Chair: Peter Wright, Vanderbilt University

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)
• Occupational exposure to birds (no known pathogenicity of avipox for birds)
• Previous immunization against rabies
• Women who have undergone hysterectomy
• Episode of severe diarrhea within one week prior to immunization
• Abnormal pelvic exam with evidence of sexually transmitted disease or other genital tract infection or trauma, including vaginitis, cervicitis, ecchymosis, vulvar or cervicovaginal lesions or abrasions or chronic cervical and/or abnormal PAP smear changes
• Recent history of rectal bleeding or repeatedly positive hemoccult test (within 1 month)

STUDY GOALS

The primary objective is to compare the safety of ALVAC-HIV vCP205 to that of ALVAC-RG vCP65 rabies glycoprotein, delivered by a variety of mucosal routes.

The secondary objectives are to:

• To evaluate the antibody, humoral and cellular immune responses resulting from priming with ALVAC vCP205
• To derive preliminary data on responses from different routes of administration of vaccine to stimulate genital and rectal immune responses using ALVAC-HIV vCP205 and the rabies construct, ALVAC-RG by determining:
  • Local (mucosal) HIV-specific antibody response in parotid saliva, nasal, rectal and genital secretions after vaccination
  • CD8+ and CD4+ cytotoxic T lymphocyte (CTL) activity specific for HIV-1, in particular CTL to gag and envelope, including the frequency and time course of the CTL response to ALVAC-HIV vCP205
  • HIV-1 antigen-specific lymphoproliferation (indicative of immunological memory)
  • HIV-1 MN antigen specific binding antibodies in serum
  • Serum neutralizing antibodies to HIV-1 MN
  • Serum antibodies that block binding of gp120 to soluble CD4+
  • Serum antibody-dependent cellular cytotoxicity
• To evaluate serum and mucosal antibody response to ALVAC-RG, a known potent immunogen.