title: Intradermal vaccination of HIV-infected patients with short HIV Gag p24-like peptides induces CD4 + and CD8 + T cell responses lasting more than seven years.
abstract: BACKGROUND
  Vacc-4x contains 4 HIV p24-like short peptides. In a previous phase II trial this immunized 90% of 38 patients on antiretroviral treatment (ART) after intradermal delivery in conjunction with local granulocyte-macrophage colony-stimulating factor (GM-CSF) as adjuvant. In this study, 22 responders were retested for cellular memory at a median 7.3 y after their last immunization. All had resumed effective ART after an interspersed ART-free median interval of 2.2 y.
  
  
  METHODS
  Vacc-4x as 15-mer overlapping by 2 amino acid panels and Vacc-4x consensus peptide sequences (4xCP) were used as antigens. Proliferation was determined as percentages of CFSE(dim)HLA-DR(+) 7AAD(-) CD3+ T cells of the CD4+ and CD8+ subsets after 6 days of culture. Frequencies of specific T cells in 6-h cultures were determined by interferon-γ (IFN)(+) CD4+ and IFN(+) CD8+, as well as degranulating bifunctional CD107a + IFN(+) CD8 + subsets.
  
  
  RESULTS
  Proliferative CD4+ and CD8+ responses to Vacc-4x as well as 4xCP were still present in 95% and 68%, respectively. Proliferation correlated with the Vacc-4x delayed-type hypersensitivity test (DTH) obtained after completed immunizations (CD4 + r = 0.63 (p = 0.002) and CD8 + r = 0.47 (p = 0.03)), suggesting that they represent T cell memory recall responses. The proliferative CD8+ and possibly CD4 + subset responses to 4xCP peptides correlated with Vacc-4x (r = 0.46 (p = 0.03) and r = 0.38 (p = 0.08), respectively). Forty-one percent still had Vacc-4x-specific IFN + CD4 + T cells, which correlated to corresponding frequencies of 4xCP peptides (r = 0.50, p = 0.02). CD107a(+) IFN(+) CD8 + T cell responses against Vacc-4x were found in 55%.
  
  
  CONCLUSIONS
  Evidence of long-lasting T cell memory recall responses to a peptide-based immunotherapeutic candidate for HIV-infected patients should enhance the focus on peptide-based intradermal vaccine delivery.
authors.affiliation: Department of Infectious Diseases, Oslo University Hospital, Oslo, Norway.
authors.forename: Andreas
authors.initials: A
authors.lastname: Lind
authors.forename: Maja
authors.initials: M
authors.lastname: Sommerfelt
authors.forename: Jens Olof
authors.initials: JO
authors.lastname: Holmberg
authors.forename: Ingebjørg
authors.initials: I
authors.lastname: Baksaas
authors.forename: Birger
authors.initials: B
authors.lastname: Sørensen
authors.forename: Dag
authors.initials: D
authors.lastname: Kvale
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000276:immunology; D044966:Anti-Retroviral Agents / Q000008:administration & dosage; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D005500:Follow-Up Studies; D016655:HIV Core Protein p24 / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000628:therapy*; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D007271:Injections, Intradermal; D007371:Interferon-gamma / Q000276:immunology; D052118:Lysosomal-Associated Membrane Protein 1 / Q000276:immunology; D008297:Male; D010455:Peptides / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D044966:Anti-Retroviral Agents; D016655:HIV Core Protein p24; D015789:HLA-A2 Antigen; D052118:Lysosomal-Associated Membrane Protein 1; D010455:Peptides; C494182:Vacc-4x; D007371:Interferon-gamma