title: 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.
abstract: 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.
authors.affiliation: University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, CO 80262, USA. cara.wilson@uchsc.edu
authors.forename: Cara C
authors.initials: CC
authors.lastname: Wilson
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Newman
authors.forename: Brian D
authors.initials: BD
authors.lastname: Livingston
authors.forename: Samantha
authors.initials: S
authors.lastname: MaWhinney
authors.forename: Jeri E
authors.initials: JE
authors.lastname: Forster
authors.forename: Jim
authors.initials: J
authors.lastname: Scott
authors.forename: Robert T
authors.initials: RT
authors.lastname: Schooley
authors.forename: Constance A
authors.initials: CA
authors.lastname: Benson
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D004311:Double-Blind Method; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D008297:Male; D008875:Middle Aged; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D018984:Epitopes, T-Lymphocyte; D019444:Vaccines, DNA; D007371:Interferon-gamma