title: An HIV-1 clade A/E DNA prime, recombinant fowlpox virus boost vaccine is safe, but non-immunogenic in a randomized phase I/IIa trial in Thai volunteers at low risk of HIV infection.
abstract: BACKGROUND
  Previously demonstrated safe and highly immunogenic in non-human primates, this study assessed DNA (pHIS-HIV-AE) prime, recombinant fowlpox (rFPV-HIV-AE) boost vaccines in humans.
  
  
  RESULTS
  Eight participants (6 active vaccine, 2 placebo) received all vaccinations; local and systemic reactions were mild to moderate. The percentage CD4(+) and CD8(+) T cells responding to HIV-1 Gag antigens by ICS (mean ± SD) was 0.16 ± 0.12 and 0.10 ± 0.12 for active and 0.01 ± 0.01 and 0.00 ± 0.00 for placebo vaccine respectively. The percentage of T cells responding did not reach pre-defined thresholds to be considered positive responses. Consequently, the Data Safety Monitoring Board recommended cessation of further recruitment. Existing volunteers were followed to 52 weeks.
  
  
  METHODS
  Vectors expressing homologous HIV-1 clade A/E gag, pol, env and regulatory genes or matched placebo were administered intramuscularly at weeks 0, 4, 8 (6 mg pHIS-HIV-AE) and week 12 (3.0 x 10(8) pfu rFPV-HIV-AE) in this randomized, double-blind, placebo-controlled phase I/IIa study in healthy Thai adults at low risk of HIV infection. Immunogenicity was determined by interferon-gamma and IL-2 expression using intracellular cytokine staining assay (ICS), 13 weeks after randomization. Interim analysis was performed when eight volunteers reached 16 weeks follow-up.
  
  
  CONCLUSIONS
  Vaccine candidates were generally well tolerated, but showed limited immunogenicity. Better vaccines and delivery systems are required.
authors.affiliation: HIV-NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
authors.forename: Atchriya
authors.initials: A
authors.lastname: Hemachandra
authors.forename: Rebekah L
authors.initials: RL
authors.lastname: Puls
authors.forename: Sunee
authors.initials: S
authors.lastname: Sirivichayakul
authors.forename: Stephen
authors.initials: S
authors.lastname: Kerr
authors.forename: Pattarawat
authors.initials: P
authors.lastname: Thantiworasit
authors.forename: Sasiwimol
authors.initials: S
authors.lastname: Ubolyam
authors.forename: David A
authors.initials: DA
authors.lastname: Cooper
authors.forename: Sean
authors.initials: S
authors.lastname: Emery
authors.forename: Praphan
authors.initials: P
authors.lastname: Phanuphak
authors.forename: Anthony
authors.initials: A
authors.lastname: Kelleher
authors.forename: Kiat
authors.initials: K
authors.lastname: Ruxrungtham
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004311:Double-Blind Method; D004337:Drug Carriers; D005260:Female; D005587:Fowlpox virus / Q000235:genetics; D005822:Genetic Vectors; D015658:HIV Infections / Q000517:prevention & control* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006805:Human Experimentation; D006801:Humans; D007114:Immunization / Q000379:methods*; D007117:Immunization, Secondary / Q000379:methods; D007273:Injections, Intramuscular; D008297:Male; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D013785:Thailand; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D016207:Cytokines; D004337:Drug Carriers; D010919:Placebos; D019444:Vaccines, DNA; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic