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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. Benson1,
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.
* Corresponding author. Mailing address for Cara C. Wilson: University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, CO 80262. Phone: (303) 315-6659. Fax: (303) 315-1043. E-mail: cara.wilson{at}uchsc.edu. Mailing address for Mark J. Newman: Pharmexa-Epimmune, Inc., 5820 Nancy Ridge Drive, San Diego, CA 92121. Phone: (858) 860-2500. Fax: (858) 860-2600. E-mail: mjn{at}pharmexa-epimmune.com
Published ahead of print on 9 April 2008.
Supplemental material for this article may be found at http://cvi.asm.org/.
Present address: Dynavax Technologies, 2929 Seventh Street, Suite 100, Berkeley, CA 94710.
Present address: University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093.
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.
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