title: Phase 1 safety and immunogenicity evaluation of ADMVA, a multigenic, modified vaccinia Ankara-HIV-1 B'/C candidate vaccine.
abstract: BACKGROUND
  We conducted a Phase I dose-escalation trial of ADMVA, a Clade-B'/C-based HIV-1 candidate vaccine expressing env, gag, pol, nef, and tat in a modified vaccinia Ankara viral vector. Sequences were derived from a prevalent circulating HIV-1 recombinant form in Yunnan, China, an area of high HIV incidence. The objective was to evaluate the safety and immunogenicity of ADMVA in human volunteers.
  
  
  RESULTS
  ADMVA or placebo was administered intramuscularly at months 0, 1 and 6 to 50 healthy adult volunteers not at high risk for HIV-1. In each dosage group [1x10(7) (low), 5x10(7) (mid), or 2.5x10(8) pfu (high)] volunteers were randomized in a 3:1 ratio to receive ADMVA or placebo in a double-blinded design. Subjects were followed for local and systemic reactogenicity, adverse events including cardiac adverse events, and clinical laboratory parameters. Study follow up was 18 months. Humoral immunogenicity was evaluated by anti-gp120 binding ELISA, immunoflourescent staining, and HIV-1 neutralization. Cellular immunogenicity was assessed by a validated IFNgamma ELISpot assay and intracellular cytokine staining. Anti-vaccinia binding titers were measured by ELISA. ADMVA was generally well-tolerated, with no vaccine-related serious adverse events or cardiac adverse events. Local or systemic reactogenicity events were reported by 77% and 78% of volunteers, respectively. The majority of events were of mild intensity. The IFNgamma ELISpot response rate to any HIV antigen was 0/12 (0%) in the placebo group, 3/12 (25%) in the low dosage group, 6/12 (50%) in the mid dosage group, and 8/13 (62%) in the high dosage group. Responses were often multigenic and occasionally persisted up to one year post vaccination. Antibodies to gp120 were detected in 0/12 (0%), 8/13 (62%), 6/12 (50%) and 10/13 (77%) in the placebo, low, mid, and high dosage groups, respectively. Antibodies persisted up to 12 months after vaccination, with a trend toward agreement with the ability to neutralize HIV-1 SF162 in vitro. Two volunteers mounted antibodies that were able to neutralize clade-matched viruses.
  
  
  CONCLUSIONS
  ADMVA was well-tolerated and elicited durable humoral and cellular immune responses.
  
  
  BACKGROUND
  Clinicaltrials.gov NCT00252148.
authors.affiliation: Aaron Diamond AIDS Research Center, New York, New York, United States of America. svasan@adarc.org
authors.forename: Sandhya
authors.initials: S
authors.lastname: Vasan
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Schlesinger
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Chen
authors.forename: Arlene
authors.initials: A
authors.lastname: Hurley
authors.forename: Angela
authors.initials: A
authors.lastname: Lombardo
authors.forename: Soe
authors.initials: S
authors.lastname: Than
authors.forename: Phumla
authors.initials: P
authors.lastname: Adesanya
authors.forename: Catherine
authors.initials: C
authors.lastname: Bunce
authors.forename: Mark
authors.initials: M
authors.lastname: Boaz
authors.forename: Rosanne
authors.initials: R
authors.lastname: Boyle
authors.forename: Eddy
authors.initials: E
authors.lastname: Sayeed
authors.forename: Lorna
authors.initials: L
authors.lastname: Clark
authors.forename: Daniel
authors.initials: D
authors.lastname: Dugin
authors.forename: Mar
authors.initials: M
authors.lastname: Boente-Carrera
authors.forename: Claudia
authors.initials: C
authors.lastname: Schmidt
authors.forename: Qing
authors.initials: Q
authors.lastname: Fang
authors.lastname: LeiBa
authors.forename: Yaoxing
authors.initials: Y
authors.lastname: Huang
authors.forename: Gerasimos J
authors.initials: GJ
authors.lastname: Zaharatos
authors.forename: David F
authors.initials: DF
authors.lastname: Gardiner
authors.forename: Marina
authors.initials: M
authors.lastname: Caskey
authors.forename: Laura
authors.initials: L
authors.lastname: Seamons
authors.forename: Martin
authors.initials: M
authors.lastname: Ho
authors.forename: Len
authors.initials: L
authors.lastname: Dally
authors.forename: Carol
authors.initials: C
authors.lastname: Smith
authors.forename: Josephine
authors.initials: J
authors.lastname: Cox
authors.forename: Dilbinder
authors.initials: D
authors.lastname: Gill
authors.forename: Jill
authors.initials: J
authors.lastname: Gilmour
authors.forename: Michael C
authors.initials: MC
authors.lastname: Keefer
authors.forename: Patricia
authors.initials: P
authors.lastname: Fast
authors.forename: David D
authors.initials: DD
authors.lastname: Ho
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D000293:Adolescent; D000328:Adult; D004306:Dose-Response Relationship, Immunologic; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005822:Genetic Vectors; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008297:Male; D009500:Neutralization Tests; D010919:Placebos; D014616:Vaccinia virus / Q000235:genetics*; D055815:Young Adult
chemical_list: D016915:AIDS Vaccines; D010919:Placebos