Clinical Phase 1 Safety and Immunogenicity Testing of an Epitope-based DNA Vaccine in HIV-1-infected Subjects Receiving Highly Active Antiretroviral Therapy (HAART)

University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, CO 80262; Pharmexa-Epimmune, Inc., 5820 Nancy Ridge Drive, San Diego CA 92121

^* To whom correspondence should be addressed. Email: cara.wilson{at}uchsc.edu. mjn{at}pharmexa-epimmune.com.

	Abstract

A DNA vaccine encoding sequence conserved HIV-1-derived cytotoxic T-lymphocyte (CTL) epitopes from multiple HIV-1 gene products (designated EP HIV-1090) was evaluated in a placebo controlled, dose escalation phase 1 clinical trial of HIV-1-infected subjects receiving potent combination antiretroviral therapy. Patients received four intramuscular immunizations with EP HIV-1090 over a four month period at one of 4 doses (0.5, 1.0, 2.0, 4.0 mg) or placebo. The vaccine was determined to be safe and well tolerated at all doses tested. CTL responses were measured from cryopreserved peripheral blood mononuclear cells (PBMC) using IFN- ELISPOT assays, with and without in vitro peptide stimulation (IVS). Responses to one or more vaccine epitopes were detected throughout the course of vaccination in 37.5% (12/32) and 47% (15/32) of vaccine recipients, measured without and with IVS, respectively, indicating possible vaccine-induced priming of epitope-specific T cells. However, differences in response rates to HIV-1 epitopes between vaccine and placebo recipients did not achieve statistical significance. The HIV-1 epitope-specific CTL responses measured in the peripheral blood after vaccination were often low level and short-lived, and as such, alternative immunization schedules, routes of delivery or vaccine formulations may be required to increase vaccine potency.