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.
Current Medicinal Chemistry
Title:HIV-Antigens Charged on Phosphorus Dendrimers as Tools for Tolerogenic Dendritic Cells-Based Immunotherapy
Volume: 21 Issue: 16
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
Affiliation:
Keywords: Dendritic cells, phosphorus dendrimers, nanoparticle, HIV, peptide, vaccine.
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.
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Vacas-Cordoba Enrique, Bastida Hugo, Pion Marjorie, Hameau Aurelien, Ionov Maksim, Bryszewska Maria, Caminade Marie Anne, Majoral Pierre Jean and Munoz-Fernandez Maria-Angeles, HIV-Antigens Charged on Phosphorus Dendrimers as Tools for Tolerogenic Dendritic Cells-Based Immunotherapy, Current Medicinal Chemistry 2014; 21 (16) . https://dx.doi.org/10.2174/0929867321666131129114022
DOI https://dx.doi.org/10.2174/0929867321666131129114022 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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