Protocol 023

OUTLINE OF PROTOCOL 023

A PHASE I TRIAL TO EVALUATE THE SAFETY AND IMMUNOGENICITY OF THE UBI^® HIV-1 MN PND PEPTIDE IMMUNOGEN, GIVEN BY IM INJECTION, IN COMBINATION WITH THE UBI^® MICROPARTICULATE MONOVALENT HIV-1 MN BRANCHED PEPTIDE, GIVEN ORALLY, IN HIV-1 UNINFECTED VOLUNTEERS

Subjects: Healthy, HIV-1 uninfected (seronegative) adults aged 18-60 with low or intermediate risk for HIV infection; at least 5 of the volunteers in each group (I and II) will be women.

Schema:

Group*	Accrual	IM PRIME		ORAL BOOST (MONTH)
Group*	Accrual	Month 0	Injection Site	1	2	8
I	12	500 µg MN V3 peptide in alum	Deltoid	3 mg MN V3 microparticles	3 mg MN V3 microparticles	3 mg MN V3 microparticles
I	4	Alum placebo	Deltoid	Microparticulate placebo	Microparticulate placebo	Microparticulate placebo
II	12	500 µg MN V3 peptide in alum	Anterior Thigh	3 mg MN V3 microparticles	3 mg MN V3 microparticles	3 mg MN V3 microparticles
	4	Alum placebo	Anterior Thigh	Microparticulate placebo	Microparticulate placebo	Microparticulate placebo
Total	n = 36**

* Treatment group omitted to preserve blinding
** Total includes 4 additional volunteers added in 08/95

ACCRUAL, IMMUNIZATIONS AND FOLLOW-UP COMPLETED

Product Description:

The HIV-1 MN V3 (PND) immunogen is a synthetic peptide prototype vaccine based on eight V3-derived homologous peptides attached to a heptalysyl core to form radially branched structures and formulated in alum. [United Biomedical, Inc.]
Microparticulate monovalent HIV-1 MN branched peptide vaccine is a branched peptide immunogen consisting of eight V3-derived homologous peptides attached to a heptalysyl core to form radially branched structures, and entrapped in microparticles from polymers, the polylactide co-glycosides and polylactide. [United Biomedical, Inc.]

Time Period: First volunteer entered on 05/18/95 and the last on 02/15/96; follow-up of 60 weeks.

Clinical Sites: University of Alabama at Birmingham, University of Rochester and University of Washington

Study Chair: Mark Mulligan, University of Alabama

INCLUSION CRITERIA

Standard inclusion criteria.

EXCLUSION CRITERIA

Standard inclusion criteria.

STUDY GOALS

To determine whether oral immunization with UBI^® microparticulate monovalent HIV-1 MN branched peptide vaccine in HIV-1 uninfected volunteers, when preceded by parenteral priming with UBI^® HIV-1 MN PND peptide immunogen, is safe in healthy HIV-negative adult volunteers.
To determine if oral immunization with UBI microparticulate monovalent HIV-1 MN branched peptide vaccine in HIV-1 uninfected volunteers, when preceded by parenteral priming with UBI^® HIV-1 MN PND peptide immunogen, provides superior genital mucosal and systemic immune responses relative to an all oral regimen or when the oral immunization precedes the parental immunization (AVEG Protocol 018).
To compare parenteral priming with UBI^® HIV-1 MN PND peptide immunogen by IM injection into the deltoid versus anterior thigh; the latter site drains to inguinal lymph nodes and may induce better mucosal immune responses at genital/rectal mucosal sites.
To determine whether an accelerated schedule of oral boosts at Months 1 and 2 after IM priming is sufficient for induction of both genital mucosal and systemic HIV-specific immune responses.