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Volume 6 Supplement 3

AIDS Vaccine 2009

P18-10. Ability of HIV antigens-pulsed monocyte-derived dendritic cells to induce HIV-specific T cell response: potential use in therapeutic vaccine

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Background

Despite 20 years of effort, the design of an effective HIV-1 vaccine remains an enormous challenge. In this scenario, new immunological approaches must be considered. Dendritic cells-based vaccines have been widely used in cancer therapy showing interesting successful results. More recently, Lu et al. (2004) described large reductions on virus load in untreated HIV-infected patients immunized with autologous DC pulsed with inactivated viruses. Although encouraging, these results showed sustained virus reduction in only half of vaccinees. Besides, isolating virus from each patient is a rather laborious and expensive process. Based on that monocyte-derived dendritic cell (Mo-DC) vaccine model we evaluated the use of alternative HIV products in order to simplify the process of vaccine production, reduce costs and achieve protective immune responses on a greater number of individuals.

Methods

Monocytes from HIV-serodiscordant couples were differentiated in vitro into dendritic cells, pulsed with a pool of aldrithiol-2-inactivated HIV-1 subtypes or the HIV-1IIIB p55Gag protein and then cultured with autologous lymphocytes for 7 days. At day 7, the culture received a boost of fresh Mo-DCs pulsed with the same antigens. The T lymphocyte immunological response was determined by proliferation assay, IFNγ production and cellular activation. The Mo-DC phenotype was also evaluated.

Results

Mo-DCs were shown to be fully matured and activated (CD11c+HLA-DRhiCD86hiCD80hiCD83+) in both antigen-pulsing protocols. IFNγ production by T CD4+ and CD8+ lymphocytes, as well as the percentage of CD38+ cells, was always higher when stimulated with pulsed Mo-DCs compared to non-pulsed cells. The T lymphocyte proliferation of pulsed Mo-DCs was also significant greater compared to the non-pulsed condition, being slightly but not significantly higher in p55Gag-pulsed cells.

Conclusion

This easier and cheaper Mo-DC vaccine model elicited in vitro detectable cellular immune responses in HIV-uninfected subjects, which suggests a broader range of action and represents a viable and promising alternative of therapeutic vaccination.

Author information

Correspondence to GG Silveira.

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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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Silveira, G., Oshiro, T., Almeida, A. et al. P18-10. Ability of HIV antigens-pulsed monocyte-derived dendritic cells to induce HIV-specific T cell response: potential use in therapeutic vaccine. Retrovirology 6, P319 (2009). https://doi.org/10.1186/1742-4690-6-S3-P319

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Keywords

  • Protective Immune Response
  • Therapeutic Vaccination
  • Autologous Lymphocyte
  • Virus Reduction
  • Vaccine Model