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Clinical and Vaccine Immunology, June 2008, p. 986-994, Vol. 15, No. 6
1071-412X/08/$08.00+0     doi:10.1128/CVI.00492-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Clinical Phase 1 Testing of the Safety and Immunogenicity of an Epitope-Based DNA Vaccine in Human Immunodeficiency Virus Type 1-Infected Subjects Receiving Highly Active Antiretroviral Therapy ^,

Cara C. Wilson,^1* Mark J. Newman,^2* Brian D. Livingston,^2, Samantha MaWhinney,¹ Jeri E. Forster,¹ Jim Scott,¹ Robert T. Schooley,^1, and Constance A. Benson^1,

University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, Colorado 80262,¹ Pharmexa-Epimmune, Inc., 5820 Nancy Ridge Drive, San Diego, California 92121²

Received 18 December 2007/ Returned for modification 28 January 2008/ Accepted 28 March 2008

A DNA vaccine encoding sequence-conserved human immunodeficiency virus type 1 (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 4-month period at one of four doses (0.5, 1.0, 2.0, or 4.0 mg) or received a 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 using gamma interferon enzyme-linked immunospot 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 rates of response 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 therefore, alternative immunization schedules, routes of delivery, or vaccine formulations may be required to increase vaccine potency.

Published ahead of print on 9 April 2008.

Supplemental material for this article may be found at http://cvi.asm.org/.

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Present address: University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093.