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Volume 6 Supplement 3

AIDS Vaccine 2009

P18-02. Peptide pulsed dendritic cells allows for induction of polyfunctional CD4+ T cell responses and help CD8+ T cell targeting subdominant CTL epitopes

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Background

To target HIV-1 specific CTL epitopes that are subdominant in the context of natural infection we designed a peptide based vaccine in order to induce a balanced CD4+ and CD8+ cellular immune response. We believe that inducing CD4+ T cell responses would provide help and allow for responses against sub-dominant epitopes to come forward.

Methods

In a phase I/II therapeutic HIV-1 vaccine trial 12 treatment naïve HIV-1 infected Danish individuals received 1 × 10e7 autologous monocyte derived dendritic cells s.c. (week 0, 2, 4 and 8) pulsed with 10 different peptides, 7 CTL epitopes from conserved regions of HIV-1 and two HIV-1 derived and one universal T helper epitope. Novel T cell responses were evaluated by intracellular cytokine staining for IFN-γ, TNF-α and IL-2.

Results

This mode of vaccination generated robust polyfunctional vaccine specific CD4+ T cell responses sustained at the last evaluation, 6 months after the last immuniza-tion. Cytokine responses were dominated by TNF-α and IL-2 production, indicative of long-lived central memory cells. Moreover, in 12 out of 12 patient's vaccine specific CD8+ T cell responses were detected.

Conclusion

This suggests that this mode of vaccination, dendritic cells loaded with a combination of T helper and CTL epitope peptides, is a successful approach to target subdominant epitopes and the possibility to re-direct the immune response towards selected epitopes during chronic HIV-1 infection is an important proof of concept.

Author information

Correspondence to A Fomsgaard.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Fomsgaard, A., Karlsson, I., Kløverpris, H. et al. P18-02. Peptide pulsed dendritic cells allows for induction of polyfunctional CD4+ T cell responses and help CD8+ T cell targeting subdominant CTL epitopes. Retrovirology 6, P311 (2009). https://doi.org/10.1186/1742-4690-6-S3-P311

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Keywords

  • Intracellular Cytokine Staining
  • Peptide Base Vaccine
  • Helper Epitope
  • Central Memory Cell
  • Autologous Monocyte