Título:
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Quality of T-cell responses versus reduction in viral load: results from an exploratory phase II clinical study of Vacc-4x, a therapeutic HIV vaccine
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Autor/a:
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Ellefsen-Lavoie, K.; Rockstroh, J.; Pollard, R.; Pantaleo, G.; Podzamczer Palter, Daniel; Asmuth, D.; van Lunzen, J; Arasteh, K.; Schumann, D.; Peters, B.; Clotet, B.; Hardy, D.; Lazzarin, A.; Gatell, J.; Sommerfelt, M. A.; Baksaas, I.; Wendel-Hansen, V.; Sørensen, B.
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Abstract:
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Background
Immunization with Vacc-4x, a peptide-based therapeutic
vaccine for HIV-1, has shown a statistically significant
reduction in viral load set point compared to placebo
during treatment interruption in an exploratory phase II
clinical study enrolling 135 subjects (NCT00659789).
This vaccine aims to induce sustained cell-mediated
immune responses to conserved domains on HIV p24.
Methods
After 6 immunizations on ART over 28 weeks, treatment
was interrupted for up to 24 weeks (Vacc-4x n=88;
placebo n=38). Immunological analyses (ELISPOT, proliferation,
intracellular cytokine staining (ICS)) to HIV p24
were carried out at central laboratories. The HLA class I
profile (Vacc-4x n=73, placebo n=32) was also determined.
Results
For subjects that remained off ART until week 52 (Vacc-4x
n=56, placebo n=25), there was a log 0.44 reduction in
viral load set point between the Vacc-4x and placebo
groups (p=0.0397). There was a similar distribution of
HLA class I alleles in the two treatment arms, with the
exception of the B35 allele (27% of Vacc-4x subjects versus
8% placebo subjects). The viral load of ELISPOT positive
Vacc-4x subjects was significantly lower than that of placebo
subjects (p=0.023). There was no significant difference
in T-cell proliferation responses between Vacc-4x and placebo groups, however, the percentage of subjects showing
proliferative CD4 and CD8 T-cell responses to Vacc-4x
peptides increased over time only for the Vacc-4x group.
ICS analysis showed a predominance of CD8-mediated
T-cell responses to p24 that were significantly increased
from baseline for the Vacc-4x group (p<0.043) but not for
the placebo group(p>0.05). There was also a trend towards
higher numbers of polyfunctional T-cells in the Vacc-4x
group compared to the placebo group (p=0.188).
Conclusion
These findings suggest Vacc-4x immunization can influence
the quality of immune responses to HIV-1 p24 irrespective
of HLA status, and contribute to a reduction in viral load. |
Materia(s):
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-VIH (Virus) -Cèl·lules T -HIV (Viruses) -T cells |
Derechos:
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cc by (c) Ellefsen-Lavoie, et al., 2012
http://creativecommons.org/licenses/by/3.0/es/ |
Tipo de documento:
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Artículo Artículo - Versión publicada |
Editor:
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BioMed Central
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