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45 The Multispecific B- and T-Cell Responses Induced in Humans by an HIV-1 Lipopeptide Vaccine Can Be Sustained over a Period of up to Two Years
H. Gahéry-Ségard*1, G. Pialoux2, S. Figueiredo1, M. Sureneau1, C. Igéa1, J.-P. Lévy1, H. Gras-Masse3, and J.-G. Guillet1
1 Hosp. Cochin, INSERM U445, Paris, France; 2 Hosp. Rothschild, Paris, France; and 3CNRS URA1309, Inst. Pasteur de Lille, France
Background: We have developed an anti-HIV lipopeptide vaccine using HIV-specific large peptides modified by C-term addition of a single palmitoyl chain. A phase I study was conducted to assess the safety and immunogenicity of a mixture of 6 lipopeptides injected alone or with QS21 adjuvant, in 28 healthy, HIV-1-uninfected volunteers. We have showed that HIV-1 lipopeptides are well tolerated and are able to induce a strong multiepitopic B- and T-cell responses in humans already after 3 injections. Our next objectives were to test the booster effect after a fourth injection and the memory immune response measured 2 years after the first injection of the vaccine.
Methods: Anti-HIV-peptide antibodies were detected by ELISA and Western blotting. Induction of cellular immune responses was assessed by proliferative, 51Cr release assays and ELISPOT.
Results: An increasing immune response was observed after a fourth injection of the lipopeptide vaccine at week W52. At this point every volunteer except 2 had shown an antibody response, and a CD4+ T-cell response was obtained in 92% of the volunteers. The anti-HIV cytotoxic CD8+ T-cell responses were tested by a classical 51Cr release assay in 13 volunteers; 9 (69%) had clear responses. Finally, to better characterize the CD8+ response we used an IFN-gamma ELISPOT method and a bank of 60 HIV-1 epitopes. A retrospective CD8+ T-cell study was conducted over the 2-year period in 22 out of the 28 volunteers. Our work on the CD8+ responses is still on-going, but we have already detected a specific response at W20 in 12 out of the 16 volunteers tested (75%). After the fourth injection, a specific CD8+ T-cell response was observed in 20 out of 22 volunteers, and 12 (60%) of them gave multispecific responses. A sustained CD8+ T-cell response was detected in 70% of the volunteers.
Conclusions: Lipopeptides are promising vectors for an AIDS vaccine.
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