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Submitted on 13 Sep 2012
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Targeting HIV Gag p24 to DICR on dendritic cells
induces T cell and potent and long-lasting antibody
responses in non-human primates
Anne-Laure Flamar, Roger Le Grand, Vanessa Contreras, Sandra Zurawski,
Nathalie Dereuddre-Bosquet, Isabelle Mangeot, Frédéric Martinon, Sangkon
Oh, Jacques Banchereau, Gérard Zurawski, et al.
To cite this version:
Anne-Laure Flamar, Roger Le Grand, Vanessa Contreras, Sandra Zurawski, Nathalie
Dereuddre-Bosquet, et al.. Targeting HIV Gag p24 to DICR on dendritic cells induces T cell and potent and
long-lasting antibody responses in non-human primates. Retrovirology, BioMed Central, 2012, 9
(Suppl 2), pp.P358. �inserm-00731781�
P O S T E R P R E S E N T A T I O N
Open Access
Targeting HIV Gag p24 to DICR on dendritic cells
induces T cell and potent and long-lasting
antibody responses in non-human primates
A Flamar
1*, R Le Grand
2, V Contreras
2, S Zurawski
1, N Dereuddre-Bosquet
2, I Mangeot
2, F Martinon
2, S Oh
1,
J Banchereau
1, G Zurawski
1, Y Levy
3From
AIDS Vaccine 2012
Boston, MA, USA. 9-12 September 2012
Background
Targeting Dendritic Cells (DCs) with anti-DC receptor antibody-antigen fusion proteins is a novel approach in vaccine development for inducing potent humoral and cellular immune responses.
Methods
We engineered an human DCIR recombinant anti-body cross-reacting with the cynomolgus macaque recep-tor fused via the heavy chain C-terminus to HIV-1 Gagp24 protein (anti-DCIR.Gagp24). HIV patient PBMC cultures were incubated with anti-DCIR and control hIgG4.Gagp24 fusion proteins. After 10 days, the total T cells were challenged with HIV Gagp24 peptide pools, and then antigen-specific cytokine production was detected using intracellular staining. Macaques were also immu-nized i.d. 3 times with anti-DCIR.Gagp24 or control hIgG4.Gagp24 with or without polyI:C. Gagp24-specific IgG titers from serum were measured by ELISA and the magnitude of the antigen-specific IFNg responses was assessed by ELISPOT.
Results
In vitro, low doses of anti-DCIR Gagp24 prototype vac-cine, but not the control hIgG4.Gagp24, expand of Gagp24-specific T cells. These in vitro-expanded anti-gen-specific T cells were multifunctional, simultaneously producing multiple cytokines (IFNg, TNFa and MIP-1b). In vivo, in non-adjuvanted naïve animals, serum anti-Gagp24 antibodies were detectable 2 weeks after priming and titers were substantially increased after the 1st and
the 2nd boost with anti-DCIR.Gagp24 and were durable, while in the control hIgG4.Gagp24 group the responses were minimal. Poly I:C increased the magnitude of the responses in the anti-DCIR.Gagp24 and hIgG4.Gagp24 groups to a similar level in both groups. T cell responses induced by anti-DCIR Gagp24 could be enhanced after priming with a recombinant modified vaccinia virus Ankara (MVA) encoding HIV Gag/Pol/Nef. Boosting with anti-DCIR.Gagp24 plus poly I:C generated high titers of anti-Gagp24 antibody titers and strongly enhanced IFNg-producing T cells following priming with MVA HIV Gag/Pol/Nef.
Conclusion
Our results demonstrate that heterologous prime-boost immunization with vectors and DC-targeting protein-based vaccines is a promising vaccination approach to optimize humoral and cellular immunity for therapeutic and preventive applications against AIDS.
Author details
1Baylor Institute for Immunology Research, Dallas, TX, USA.2CEA,
Fontenay-aux-Roses, France.3INSERM U955, Faculté de Médecine de Créteil, Creteil, France.
Published: 13 September 2012
doi:10.1186/1742-4690-9-S2-P358
Cite this article as:Flamar et al.: Targeting HIV Gag p24 to DICR on dendritic cells induces T cell and potent and long-lasting antibody responses in non-human primates. Retrovirology2012 9(Suppl 2):P358.
1Baylor Institute for Immunology Research, Dallas, TX, USA
Full list of author information is available at the end of the article Flamar et al. Retrovirology 2012, 9(Suppl 2):P358
http://www.retrovirology.com/content/9/S2/P358
© 2012 Flamar et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.