Protocol 018

OUTLINE OF PROTOCOL 018

A PHASE I SAFETY AND IMMUNOGENICITY STUDY TRIAL OF UBI® MICROPARTICULATE MONOVALENT HIV-1 MN PEPTIDE IMMUNOGEN IN HIV-1 SERONEGATIVE HUMAN SUBJECTS

Subjects: Healthy, HIV-1 uninfected ( seronegative) adult volunteers without identifiable higher-risk behavior for HIV-1 infection, as determined by comprehensive screening questionnaire.

Schema:

Group	Accrual	Vaccination Schedule (Days)
		ORAL ROUTE¹ (mg)									IM² (µg)
		0	1	2	28	29	30	168	169	170	252
I	12	1	1	1	1	1	1	1	1	1	500
	4	0	0	0	0	0	0	0	0	0	0
II	12	3			3			3			500
	4	0			0			0			0
Total n = 32*

¹ Microparticulate monovalent HIV-1 MN V3 peptide or placebo
² Study Extension: HIV-1 MN V3 (PND) peptide immunogen or alum placebo
* Total of 33 volunteers enrolled.

ACCRUAL, IMMUNIZATIONS, AND FOLLOW-UP COMPLETED

Product Description:

Microparticulate monovalent HIV-1 MN V3 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; specifically, the polylactide co-glycosides and polylactide. [United Biomedical, Inc.]
HIV-1 MN V3 (PND) 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.]

Time Period: First volunteer enrolled on 06/27/94 and the last on 01/09/95; follow-up extended to 6 months after the last immunization

Clinical Sites: Johns Hopkins University, University of Alabama at Birmingham, University of Rochester

Study Chair: John Lambert, Johns Hopkins University

INCLUSION CRITERIA

Standard inclusion criteria.

EXCLUSION CRITERIA

Standard exclusion criteria.

STUDY GOALS

The aims of this Phase I study are to evaluate the safety and immunogenicity of a new microparticulate formulation of an HIV-1 MN PND peptide, for oral administration in healthy, HIV-1 seronegative adult volunteers. Specific questions to be addressed include:

Are there any adverse clinical reactions or laboratory evidence of toxicity to the candidate vaccine (i.e., local or systemic reactions or immunologic impairment)?
Does the candidate vaccine induce anti-HIV-1 antibodies? In particular, does it stimulate homologous and heterologous anti-HIV-1 neutralizing antibody in healthy volunteers?
Does administration of the candidate vaccine stimulate secretory IgA in mucosal secretions?
Does the candidate vaccine stimulate cell-mediated immune responses including CD4+ and CD8+ cytotoxic T-cell activity and lymphocyte proliferation?
To compare the administration of the candidate vaccine by a single dose administration versus three sequential daily administrations.

Study extension: To measure the safety and immunogenicity of IM administration of HIV-1 MN V3 (PND) peptide immunogen after 3 oral doses of the microparticulate monovalent peptide immunogen.