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Volume 6 Supplement 3

AIDS Vaccine 2009

P17-15. Immunogenicity studies of chimeric yellow fever 17D viruses carrying HIV-1 p24 antigen

Background

We reported previously the construction, in vitro characterization and preliminary immunogenicity studies of a novel recombinant 17D yellow fever vaccine expressing HIV-1 p24 (17Dp24). Here we further evaluated 17Dp24-induced Ag-specific cell-mediated immune responses as well as compared this p24-specific immune reactions to those of other viral vectors (MVA and Ad) carrying the same HIV-1 antigen with the goal to compare the quantity and quality of the different immune responses.

Methods

The Ag-specific polyfunctional T cell response was measured by multi-parameter intracellular cytokine staining (ICS) and cytokine release was measured by cytokine beads array(CBA). The quality of 17Dp24 induced cell-mediated immunity was further investigated with a mouse challenge model using a recombinant vaccinia virus expressing HIV-Gag (including p24).

Results

Mouse immunogenicity experiments indicated that the 17Dp24 vaccine candidates were able to induce a robust CD8+ and CD4+ T-cell response. Upon Ag stimulation in vitro, INFγ, IL-2 as well as the expression of both cytokines were observed in up to 1.5% of both T-cell populations. Although a 1,5-fold greater INFγ CD8+ T-cell response is generated for MVA and Ad5 when comparing the immune responses with those of our 17D recombinants, two to threefold more polyfunctional CD4+ and CD8+ T-cells, expressing both INFγ and IL-2, was noticed for the recombinant 17D viruses. Furthermore in contrast to the other vectors 17D recombinants were also able to generate IL-4 and IL-5 producing Ag-specific CD4+ T-cells. Lastly, viral titers were reduced 100-fold when mice previously immunized with the 17Dp24 vaccine candidate were challenged with the vaccinia-Gag virus, indicating a functional 17Dp24 induced cell-mediated immune response.

Conclusion

These studies confirmed that the 17D yellow fever virus vaccine strain could be pursued as alternative viral vector for HIV vaccine development.

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Correspondence to D Franco.

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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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Franco, D., Rosas, C., Rice, C. et al. P17-15. Immunogenicity studies of chimeric yellow fever 17D viruses carrying HIV-1 p24 antigen. Retrovirology 6, P297 (2009). https://doi.org/10.1186/1742-4690-6-S3-P297

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Keywords

  • Yellow Fever Virus
  • Yellow Fever Vaccine
  • Immunogenicity Study
  • Virus Vaccine Strain
  • Cytokine Bead Array