title: Phase 1 safety and immunogenicity evaluation of ADVAX, a multigenic, DNA-based clade C/B' HIV-1 candidate vaccine.
abstract: BACKGROUND
  We conducted a Phase I dose escalation trial of ADVAX, a DNA-based candidate HIV-1 vaccine expressing Clade C/B' env, gag, pol, nef, and tat genes. Sequences were derived from a prevalent circulating recombinant form in Yunnan, China, an area of high HIV-1 incidence. The objective was to evaluate the safety and immunogenicity of ADVAX in human volunteers.
  
  
  RESULTS
  ADVAX or placebo was administered intramuscularly at months 0, 1 and 3 to 45 healthy volunteers not at high risk for HIV-1. Three dosage levels [0.2 mg (low), 1.0 mg (mid), and 4.0 mg (high)] were tested. Twelve volunteers in each dosage group were assigned to receive ADVAX and three to receive placebo in a double-blind design. Subjects were followed for local and systemic reactogenicity, adverse events, and clinical laboratory parameters. Study follow up was 18 months. Humoral immunogenicity was evaluated by anti-gp120 binding ELISA. Cellular immunogenicity was assessed by a validated IFNgamma ELISpot assay and intracellular cytokine staining. ADVAX was safe and well-tolerated, with no vaccine-related serious adverse events. Local and systemic reactogenicity events were reported by 64% and 42% of vaccine recipients, respectively. The majority of events were mild. The IFNgamma ELISpot response rates to any HIV antigen were 0/9 (0%) in the placebo group, 3/12 (25%) in the low-dosage group, 4/12 (33%) in the mid-dosage group, and 2/12 (17%) in the high-dosage group. Overall, responses were generally transient and occurred to each gene product, although volunteers responded to single antigens only. Binding antibodies to gp120 were not detected in any volunteers, and HIV seroconversion did not occur.
  
  
  CONCLUSIONS
  ADVAX delivered intramuscularly is safe, well-tolerated, and elicits modest but transient cellular immune responses.
  
  
  BACKGROUND
  Clinicaltrials.gov NCT00249106.
authors.affiliation: Aaron Diamond AIDS Research Center, New York, New York, United States of America. svasan@adarc.org
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authors.lastname: Vasan
authors.forename: Sarah J
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authors.lastname: Schlesinger
authors.forename: Yaoxing
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authors.lastname: Huang
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authors.lastname: Lombardo
authors.forename: Zhiwei
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authors.forename: Phumla
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authors.lastname: Adesanya
authors.forename: Catherine
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authors.lastname: Bunce
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authors.lastname: Boaz
authors.forename: Rosanne
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authors.lastname: Boyle
authors.forename: Eddy
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authors.lastname: Sayeed
authors.forename: Lorna
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authors.lastname: Dugin
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authors.lastname: Seamons
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authors.lastname: Dally
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authors.forename: Carol
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authors.lastname: Markowitz
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authors.lastname: Cox
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authors.lastname: Gill
authors.forename: Jill
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mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D000293:Adolescent; D000328:Adult; D004306:Dose-Response Relationship, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D015483:HIV Antibodies / Q000096:biosynthesis; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D016915:AIDS Vaccines; D015483:HIV Antibodies