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Volume 6 Supplement 3

AIDS Vaccine 2009

P19-56 LB. Priming with SOCS-1 silenced Dendritic cells induces robust HIV-specific CTL response in a novel HLA-A2 transgenic humanized mouse model

Background

Cytotoxic T lymphocytes (CTL) are thought to play a central role in protection against HIV infection. This has been a major impetus for the design and testing of vaccines capable of eliciting a broad and vigorous CTL response to prevent or as a lesser goal, to ameliorate the disease course and viral transmission.

Methods

A chimeric peptide containing a 12-mer DC binding moiety fused to nonamer D-arginine residues (9dR) was developed for potential DC-specific siRNA delivery in vivo.

Results

Targeted silencing of SOCS-1 in human DCs a) enhanced their cytokine responses to LPS and stimulated a strong mixed lymphocyte reaction in vitro, b) elicited a strong primary in vitro response to HLA-A2-restricted Melan-A/MART-1 and HIV Gag SL9 epitope in naïve CD8+ T cells from healthy donors and c) increased the HIV gag-specific cytokine response in CD8 T cells from seropositive subjects. More importantly, in HLA-A2 transgenic NOD/SCID-iL2rγ-/- mice reconstituted with CD34 HSC from HLA-A2 donors, injection of SOCS-1 silenced DCs pulsed with HIV A2-restricted gag peptides, but not the irrelevant flu peptide, gave rise to a robust HIV specific CD8 T cell response which protected effectively against lethal challenge with recombinant HIV Gag-vaccinia.

Conclusion

These results demonstrate the feasibility of using targeted RNAi to manipulate DC as a strategy to boost the immunogenicity of CTL epitope vaccines for HIV and attest to the value of the novel HLA-transgenic humanized mouse model in dissecting the protective role of HIV specific CD8 T cells restricted by specific HLA- alleles.

Author information

Correspondence to S Subramanya.

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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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Subramanya, S., Armant, M., Kim, S. et al. P19-56 LB. Priming with SOCS-1 silenced Dendritic cells induces robust HIV-specific CTL response in a novel HLA-A2 transgenic humanized mouse model. Retrovirology 6, P420 (2009). https://doi.org/10.1186/1742-4690-6-S3-P420

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Keywords

  • Mixed Lymphocyte Reaction
  • siRNA Delivery
  • Humanize Mouse Model
  • Strong Primary
  • Chimeric Peptide