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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

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HAL Id: inserm-00731781

https://www.hal.inserm.fr/inserm-00731781

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�

(2)

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

3

From

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.

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