title: HLA- and dose-dependent immunogenicity of a peptide-based HIV-1 immunotherapy candidate (Vacc-4x).
abstract: OBJECTIVE
  The Vacc-4x immunotherapy candidate is composed of four modified peptides corresponding to conserved domains of the HIV-1 protein p24 that preferentially include HLA-A2 restricted elements. Dose-dependent safety and immunogenicity of Vacc-4x and the significance of a HLA-A2 haplotype were examined.
  
  
  METHODS
  Non-AIDS, HIV-1 infected healthy patients (n = 40) stable on HAART with CD4 counts > 300 x 10 cells/l were randomized to receive either low-dose or high-dose Vacc-4x over 26 weeks in an open, prospective phase II clinical trial.
  
  
  METHODS
  Patients received a total of 10 intradermal injections, using recombinant granulocyte-macrophage colony stimulating factor as a local adjuvant. Vacc-4x-specific cellular responses were monitored in vivo by delayed-type hypersensitivity (DTH) skin test infiltrates and in vitro by both T-cell proliferation, and induction /secretion of cytokines.
  
  
  RESULTS
  Most patients developed Vacc-4x-specific DTHs (90%) and proliferative T-cell responses (80%) that were inter-related in magnitude. High-dose Vacc-4x generally induced stronger specific immune responses than low dose in terms of DTH areas and CD4 and CD8 T-cell proliferation. Only HLA-A2 negative patients had a definite dose advantage, and this subgroup had in fact the best overall DTH and proliferative responses. In contrast, no significant dose difference was observed for HLA-A2 positive patients. No serious adverse events were reported.
  
  
  CONCLUSIONS
  HIV-associated specific responses were safely induced in most patients by Vacc-4x in a dose-dependent manner and were also influenced by the HLA haplotype.
authors.affiliation: Ullevål University Hospital, University of Oslo, Department of Infectious Diseases, Oslo, Norway. a.m.b.kran@medisin.uio.no
authors.forename: Anne-Marte B
authors.initials: AM
authors.lastname: Kran
authors.forename: Birger
authors.initials: B
authors.lastname: Sørensen
authors.forename: Jørgen
authors.initials: J
authors.lastname: Nyhus
authors.forename: Maja A
authors.initials: MA
authors.lastname: Sommerfelt
authors.forename: Ingebjørg
authors.initials: I
authors.lastname: Baksaas
authors.forename: Johan N
authors.initials: JN
authors.lastname: Bruun
authors.forename: Dag
authors.initials: D
authors.lastname: Kvale
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000276:immunology*; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D007167:Immunotherapy / Q000379:methods*; D011446:Prospective Studies; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D016207:Cytokines; D015789:HLA-A2 Antigen; C494182:Vacc-4x