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. DESIGN: 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.
RCT Entities:
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. DESIGN:Non-AIDS, HIV-1 infected healthypatients (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: Frank O Pettersen; Eirik A Torheim; Anders E A Dahm; Ingeborg S Aaberge; Andreas Lind; Malin Holm; Einar M Aandahl; Per M Sandset; Kjetil Taskén; Dag Kvale Journal: J Virol Date: 2011-04-13 Impact factor: 5.103
Authors: Leonard Moise; R Mark Buller; Jill Schriewer; Jinhee Lee; Sharon E Frey; David B Weiner; William Martin; Anne S De Groot Journal: Vaccine Date: 2010-11-04 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: Paolo Palma; Lindvi Gudmundsdotter; Andrea Finocchi; Lars E Eriksson; Nadia Mora; Veronica Santilli; Angela Aquilani; Emma C Manno; Paola Zangari; Maria Luisa Romiti; Carla Montesano; Alba Grifoni; Andreas Brave; Karl Ljungberg; Pontus Blomberg; Stefania Bernardi; Eric Sandström; Bo Hejdeman; Paolo Rossi; Britta Wahren Journal: Vaccines (Basel) Date: 2014-07-17