Abstract
Finding a functional cure for HIV-1 infection will markedly decrease the social and economic burden of this disease. In this work, we have taken advantage of the antigen presenting cell role of human dendritic cells (DCs) to try to induce an immune response to HIV-derived peptide delivered to DCs using two different polycationic nanoparticles: a G4 PAMAM dendrimer modified to a 70/30 ratio of hydroxyl groups/amines and a cyclodextrin derivative. We have studied peptide delivery using a fluorescence peptide and have studied the immune response generation by cytokine determination and flow cytometry. We have found a robust delivery of the antigenic peptide to DCs and activated dendritic cell-mediated peripheral blood mononuclear cells (PBMCs) proliferation using the mixed lymphocyte reaction. However, no expression of markers indicating activation of either B or T lymphocytes was observed. Moreover, the release of the pro-inflammatory cytokine TNF-α or IL-2 was only observed when DCs treated with either the dendrimer or the dendriplex containing the peptide. Antigenic peptide delivery to DCs is a promising approach to generate a vaccine against HIV-1 infection. However, more studies, including the simultaneous delivery of several antigenic peptides from different viral proteins, can markedly improve the immune response.
Highlights
Since the development and commercialization of anti-retroviral therapy (ART), HIV-1 infection is no longer a death sentence and has become a chronic infection for those patients with access to treatment [1,2,3]
The toxicity of AMC6 nanoparticle and G4-70/30 dendrimer on dendritic cells (DCs) was assessed by MTT assays
The results presented in this study show that both polycationic carriers are efficient for peptide delivery into DCs opening new approaches for potentiating DC antigen presentation
Summary
Since the development and commercialization of anti-retroviral therapy (ART), HIV-1 infection is no longer a death sentence and has become a chronic infection for those patients with access to treatment [1,2,3]. The average annual cost of ART per person was estimated to be $19,912 in 2006 and $23,000 in 2010, according to the US Center for Disease Control and Prevention (CDC), which results on an estimate average of about $380,000 for a lifetime [5]. For these reasons, finding a more accessible and long-lasting prevention/therapeutic approach against HIV-1 infection is one of the biggest current challenges of the biomedical community
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