Session 51Poster Presentations Novel Vaccine Approaches Session Day and Time: Thursday 1:30 - 3:30 pm Room: Hall D
426 Long-term Specific Immune Responses Induced in Humans by an HIV-1 Lipopeptide Vaccine: Immunodominance Ranking of CD8+ T-cell Epitopes H. Gahery-Segard*1, G. Pialoux2, S. Figueiredo1, C. Igea1, M. Surenaud1, H. Gras-Masse3, J-P. Levy
J-G. Guillet4, J-G. Guillet1 1INSERM U567, Paris, France; 2Tenon Hosp, Paris, France; 3Inst Pasteur, Lille, France; and 4Inst Pasteur, Paris, France
Background: We have shown previously that an anti-HIV lipopeptide vaccine using large peptides derived from regulatory or structural HIV-1 proteins (Nef, Gag, and Env) injected alone or with QS21 adjuvant to HIV-uninfected volunteers is well tolerated and is able to induce immune responses already after three injections (ANRS, VAC 04). In the present report, we studied the booster immunization after a 4th injection, the long-term immune response measured 2 yrs after the first injection of the vaccine, and the QS21 adjuvant effect.
Methods: This vaccine was injected alone or with QS21 adjuvant to 28 HIV-uninfected volunteers. Immunological parameters were measured before and after immunization. Anti-HIV peptide IgG antibodies were detected by ELISA and Western blotting. Anti-HIV peptide proliferative T-cell responses were evaluated by standard lymphoproliferative essay. From the vaccine, 59 HIV-1 CD8+ T-cell epitopes were identified and used with an IFN-gamma ELISpot method to characterize the anti-HIV-1 CD8+ T-cell responses.
Results: After a 4th injection of the vaccine, an increase in the specific immune response was observed. At this point, B- and T-cells were detected in over 85% of the vaccinated volunteers. A positive QS21 effect was observed when the anti-HIV long-term immune response of B- and CD4+ T-cells was evaluated. In contrast, the sustained CD8+ T-cell response was negatively modulated by this adjuvant. To better characterize the CD8+ T-cell response, we used an IFN-gamma ELISpot method and a bank of 59 HIV-1 epitopes. We showed that 29 of these epitopes induced stimulation. For the 5 most common HLA molecules (HLA-A2, -A3, -A11, -A24, and -B7 superfamily) an average of 11 (range 8-15) HIV-1 epitopes were tested per volunteer, and we observed a multi-specific CD8+ T-cell response in 68% of the positive responders. The frequency of T-cell recognition was high for Nef 68-76, Nef 71-79, Nef 84-92, Nef 135-143, Nef 137-145, Gag 259-267, Gag 260-268, Gag 263-272, Gag 267-274, Gag 267-277, and Gag 276-283. Interestingly, the broader CD8+ T-cell response observed in vaccinated volunteers was different from that observed in HIV-1 infected patients.
Conclusions: We believe that the development of an anti-HIV lipopeptide vaccine is a suitable method of inducing B- and T-cell multi-epitopic responses in humans. Lipopeptides can also be used as prime boost and elicited an strong memory CD8+ immune responses.
