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) afterintradermal 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.
RCT Entities:
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-infectedpatients should enhance the focus on peptide-based intradermal vaccine delivery.
Authors: Samir K Lakhashe; Siddappa N Byrareddy; Mingkui Zhou; Barbara C Bachler; Girish Hemashettar; Shiu-Lok Hu; Francois Villinger; James G Else; Shannon Stock; Sandra J Lee; Diego A Vargas-Inchaustegui; Egidio Brocca Cofano; Marjorie Robert-Guroff; Welkin E Johnson; Victoria R Polonis; Donald N Forthal; Erwann P Loret; Robert A Rasmussen; Ruth M Ruprecht Journal: Vaccine Date: 2014-09-20 Impact factor: 3.641
Authors: Andreas Lind; Kristin Brekke; Frank Olav Pettersen; Tom Eirik Mollnes; Marius Trøseid; Dag Kvale Journal: PLoS One Date: 2014-01-09 Impact factor: 3.240
Authors: Kristin Brekke; Andreas Lind; Carol Holm-Hansen; Inger Lise Haugen; Birger Sørensen; Maja Sommerfelt; Dag Kvale Journal: PLoS One Date: 2014-11-14 Impact factor: 3.240
Authors: Jürgen K Rockstroh; David Asmuth; Giuseppe Pantaleo; Bonaventura Clotet; Daniel Podzamczer; Jan van Lunzen; Keikawus Arastéh; Ronald Mitsuyasu; Barry Peters; Nozza Silvia; Darren Jolliffe; Mats Ökvist; Kim Krogsgaard; Maja A Sommerfelt Journal: PLoS One Date: 2019-01-30 Impact factor: 3.240