OUTLINE OF PROTOCOL 038

Subjects: Healthy, HIV-1 uninfected volunteers of both sexes, 18-60 years of age, who have participated in AVEG clinical trials 014C or 022A, and received HIV gene-containing immunogens, and are at least 2 years from their last poxvirus immunization, or who have never received candidate HIV-1 vaccination. [Total = 60]

Schema:

vCP205: ALVAC-HIV vCP205, 106.42 TCID50 given as a single IM deltoid immunization
Group	Vaccine History	N
I	014 C	20
II	022A	30*
III	Naïve to HIV vaccine studies	10
*At least 10 will have never had C8+CTL assays, and at least 15 will have a history of positive C8+CTL assays.

Product Description: ALVAC-HIV vCP205 is a recombinant canarypox vector vaccine 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. [Aventis Pasteur]

Time Period: 3 months, with one year passive follow-up

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

Study Chair: Thomas Evans, University of Rochester

INCLUSION CRITERIA

Standard inclusion criteria, with the addition of:

• Prior participation in AVEG Protocol 014C or 022A and received full immunization schedule per protocol specifications, or naïve to HIV-vaccine studies
• Received the last prior poxvirus HIV administration > 24 months prior to immunization in this trial
• Negative evaluation for HIV within 8 weeks of immunization in this protocol
• Received the last prior poxvirus HIV vaccine administration > 24 months prior to immunization in this trial

EXCLUSION CRITERIA

Standard exclusion criteria, with the addition of:

• Immediate type hypersensitivity reaction to egg products or neomycin (used to prepare ALVAC vaccines)

STUDY GOALS

• To evaluate the safety and tolerability of vCP205 when administered intramuscularly to naive volunteers and previous poxvirus vaccinees in Protocols 022A and 014C with previously positive or negative CD8+ CTL responses.
• To evaluate the rate and magnitude of CTL and lymphoproliferative responses in these volunteers before and after immunization to both the env and gag gene products.
• To evaluate the kinetics of the recall response using ELISPOT assays for CD4+ and CD8+ T cell function.
• To evaluate whether antibodies to the canarypox vector play a role in recall responses to encoded gene products.
• To evaluate the recall response to HIV-1 genes when vaccinia-immunized subjects from AVEG Protocol 014C are boosted by an ALVAC immunogen.
• To determine the extent of cellular vaccinia immunity induced by prior vaccinia and canarypox immunization.
• To determine the gag and env antibody responses in previously vaccinated volunteers.