- Poster presentation
- 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
© Flamar et al; licensee BioMed Central Ltd. 2012
- Published: 13 September 2012
- Peptide Pool
- Modify Vaccinia Virus Ankara
- PBMC Culture
- Preventive Application
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.
We engineered an anti-human DCIR recombinant antibody cross-reacting with the cynomolgus macaque receptor 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 immunized 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 IFNγ responses was assessed by ELISPOT.
In vitro, low doses of anti-DCIR Gagp24 prototype vaccine, but not the control hIgG4.Gagp24, expand of Gagp24-specific T cells. These in vitro-expanded antigen-specific T cells were multifunctional, simultaneously producing multiple cytokines (IFNγ, TNFα and MIP-1β). 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 IFNγ-producing T cells following priming with MVA HIV Gag/Pol/Nef.
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.
This article is published under license to 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.