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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.

AbstractBACKGROUND:
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.
AuthorsAndreas Lind, Maja Sommerfelt, Jens Olof Holmberg, Ingebjørg Baksaas, Birger Sørensen, Dag Kvale
JournalScandinavian journal of infectious diseases (Scand J Infect Dis) Vol. 44 Issue 8 Pg. 566-72 (Aug 2012) ISSN: 1651-1980 [Electronic] England
PMID22339485 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
Chemical References
  • AIDS Vaccines
  • Anti-Retroviral Agents
  • HIV Core Protein p24
  • HLA-A2 Antigen
  • Lysosomal-Associated Membrane Protein 1
  • Peptides
  • Vacc-4x
  • Interferon-gamma
Topics
  • AIDS Vaccines (administration & dosage, immunology)
  • Anti-Retroviral Agents (administration & dosage)
  • CD4-Positive T-Lymphocytes (immunology)
  • CD8-Positive T-Lymphocytes (immunology)
  • Female
  • Follow-Up Studies
  • HIV Core Protein p24 (immunology)
  • HIV Infections (immunology, therapy)
  • HLA-A2 Antigen (immunology)
  • Humans
  • Immunologic Memory (immunology)
  • Injections, Intradermal
  • Interferon-gamma (immunology)
  • Lysosomal-Associated Membrane Protein 1 (immunology)
  • Male
  • Peptides (immunology)

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