HIV-Antigens Charged on Phosphorus Dendrimers as Tools for Tolerogenic Dendritic Cells-Based Immunotherapy
Enrique Vacas-Cordoba, Hugo Bastida, Marjorie Pion, Aurelien Hameau, Maksim Ionov, Maria Bryszewska, Anne Marie Caminade, Jean Pierre Majoral and Maria-Angeles Munoz-Fernandez
Affiliation: Laboratorio InmunoBiologia Molecular, Hospital General Universitario Gregorio Maranon, Madrid, Spain.
Aims: The objective was to study if cationic phosphorus dendrimers can be used as DC-based vaccine or adjuvant
in anti-HIV-1 vaccine development when associated with HIV-1 derived peptides. Materials & Methods: The HIVderived
peptides uptake in DC and the phenotype of iDC and mDC were studied using Flow Cytometry analysis. Migration
of mDC was evaluated by an in vitro chemotaxis assay. Allogenic T-cells proliferative response induced by DC was
studied using Flow Cytometry assays. Cytokines production was analysed by Diaclon DIAplex Th1/Th2/Inflammation kit.
Results: All phosphorus dendrimers showed the ability to deliver HIV-derived peptides in DC. The phosphorus dendrimers
from second and third generations induced important changes in phenotype. Moreover, the treatment of mDC with
the second generation dendrimer and derivated dendriplexes modified cellular migratory properties, altered their capacity
to stimulate allogenic naïve T cells in vitro and impeded the production of pro-inflammatory cytokines. Conclusions: The
phosphorus dendrimers cannot be used as vaccines because they would not have the ability to induce an immune response.
The cationic phosphorus dendrimers associated with HIV-derived peptides have the ability to deliver peptides as non-viral
vectors. However, there are other potential therapeutic applications of these compounds, for instance as topical antiinflammatory
agents, as compounds for allograft rejection or autoimmune diseases and as agents inducing specific tolerance
with antigen-loaded DC against allergy reaction. Nevertheless, these applications need to be evaluated.
Keywords: Dendritic cells, phosphorus dendrimers, nanoparticle, HIV, peptide, vaccine.
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