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Volume 6 Supplement 3

AIDS Vaccine 2009

P18-13 LB. Immunogenicity of an autologous dendritic cell anti-HIV therapy in HIV-1 infected individuals

Background

The immunogenicity of an autologous dendritic cell (DC) anti-HIV therapy, AGS-004, was evaluated in a multicenter Phase 2 trial. The treatment regiment consisted of four intradermal doses, administered monthly in combination with anti-retroviral therapy (ART) followed by a well-controlled structured treatment interruption (STI). The immunotherapy consisted of monocyte-derived DC co-electroporated with CD40L in vitro transcribed (IVT) RNA along with amplified IVT RNA encoding for 4 HIV-1 antigens (GAG, NEF, REV and VPR).

Methods

Cellular immunity was determined simultaneously by lymphocyte proliferation (CFSE) and cytokine production (ICS)) multi-parameter flow cytometry assays using peripheral blood mononuclear cells from vaccinated individuals stimulated in vitro with DC electroporated with either all 4 or the individual HIV RNA. The two assays were performed according to applicable GCLP guidelines.

Results

Among 28 subjects recruited until now, there were 8 subjects that had already undergone an initial cycle of this immunotherapy (CAN-HIV-1 pilot study). All other subjects that were naïve to this immunotherapy successfully completed the immune monitoring phase of the protocol and were on a treatment interruption of varying lengths. We performed an analysis of anti-HIV-specific response by evaluating the proliferation, IFNg production and the functionality in CD8+ and CD4+ T cells stimulated with autologous Gag, Nef, Rev and Vpr. Interestingly, the absolute number of proliferating CD8+ T-cells and those producing IFNg in response to GAG-peptides showed an impressive increase after the first vaccination and following ART interruption. Preliminary results of these roll-over subjects indicate an increase in HIV-specific CD8+ T-lymphocyte polyfunctional populations following immunotherapy which is accentuated after ART treatment interruption. These populations have mainly a CD27+CD8+CD45RA- phenotype.

Conclusion

This immunotherapeutic approach may overcome the lack of polyvalent specificity of the immune response for autologous HIV-1 antigens that has been one of the reasons for the failure of prior immunotherapies that use consensus HIV-1 sequences.

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Correspondence to B Yassine Diab.

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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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Yassine Diab, B., Coutsinos, Z., Landry, C. et al. P18-13 LB. Immunogenicity of an autologous dendritic cell anti-HIV therapy in HIV-1 infected individuals. Retrovirology 6, P412 (2009). https://doi.org/10.1186/1742-4690-6-S3-P412

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Keywords

  • Flow Cytometry Assay
  • IFNg Production
  • Immune Monitoring
  • Autologous Dendritic Cell
  • Structure Treatment Interruption