Nanoparticle-Delivered HIV Peptides to Dendritic Cells a Promising Approach to Generate a Therapeutic Vaccine

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.

Cyclic Citrullinated Peptide Aptamer Treatment Attenuates Collagen-Induced Arthritis

“…It is advantageous to use NP formulations to enhance and improve the bioavailability of aptamers. , Applying NP formulations for peptide delivery and presentation to immune cells has been explored in multiple works. For example, in 2020, Martín-Moreno et al showed that the effect of peptide vaccines can be boosted by attaching the peptide to a dendrimer-based NP . The NP allows for a low-dose, s.c. administration and thereby a controlled, slow release of the aptamer to the blood.…”

New Approaches to Dendritic Cell-Based Therapeutic Vaccines Against HIV-1 Infection

“…Another recent study uses G4-70/30 PAMAM polycationic dendrimer and AMC6 nanoparticle derived from β-cyclodextrin as peptide delivery agents ( 175 ). In this work, an antigenic peptide derived from the HIV-1 gag p24 protein was used in combination with these polycationic structures, binding to specific receptors.…”

Cyclodextrin-Based Functional Glyconanomaterials

“…Polycationic cyclodextrins have become the iconic representatives in this category [ 5 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 ]. The efficiency in compacting nucleic acids into nanocomplexes (so-called CDplexes) capable of mediating cell entry and subsequent expression of the nucleic acid anticipated activity (transfection) was significantly enhanced for prototypes that can additionally establish cyclodextrin–cyclodextrin interactions through either hydrophobic [ 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 ], host–guest [ 79 , 134 ] or aromatic–aromatic contacts [ 135 , 136 , 137 , 138 , 139 , 140 , …”