HLA- and dose-dependent immunogenicity of a peptide-based HIV-1 immunotherapy candidate (Vacc-4x).
AIDS
; 18(14): 1875-83, 2004 Sep 24.
Article
em En
| MEDLINE
| ID: mdl-15353973
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.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.
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Base de dados:
MEDLINE
Assunto principal:
Infecções por HIV
/
Antígeno HLA-A2
/
HIV-1
/
Vacinas contra a AIDS
/
Hipersensibilidade Tardia
/
Imunoterapia
Tipo de estudo:
Clinical_trials
/
Observational_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
AIDS
Assunto da revista:
SINDROME DA IMUNODEFICIENCIA ADQUIRIDA (AIDS)
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
Noruega