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Current Medicinal Chemistry
ISSN (Print): 0929-8673
ISSN (Online): 1875-533X
VOLUME: 21
ISSUE: 16
DOI: 10.2174/0929867321666131129114022      Price:  $58









HIV-Antigens Charged on Phosphorus Dendrimers as Tools for Tolerogenic Dendritic Cells-Based Immunotherapy

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Author(s): Enrique Vacas-Cordoba, Hugo Bastida, Marjorie Pion, Aurelien Hameau, Maksim Ionov, Maria Bryszewska, Anne Marie Caminade, Jean Pierre Majoral and Maria-Angeles Munoz-Fernandez
Pages 1898-1909 (12)
Abstract:
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.
Affiliation:
Laboratorio InmunoBiologia Molecular, Hospital General Universitario Gregorio Maranon, Madrid, Spain.