Molecular basis of improved immunogenicity in DNA vaccination mediated by a mannan based carrier |
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| Authors: | Choon Kit Tang Kuo-Ching Sheng Sandra E. Esparon Owen Proudfoot Vasso Apostolopoulos Geoffrey A. Pietersz |
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| Affiliation: | 1. Department of Pathology, Ghent University, De Pintelaan 185, 9000 Ghent, Belgium;2. Department of Pathology, University of Michigan, Zina Pitcher Place 109, 48109 Ann Arbor, USA;3. Laboratory of Immunoregulation and Mucosal Immunology, Department of Pneumology, Ghent University, De Pintelaan 185, 9000 Ghent, Belgium;4. Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Suite 113, Biotech 2, Worcester, 01605, USA;5. Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, De Pintelaan 185, 9000 Ghent, Belgium;6. Pole Pneumologie, ORL & Dermatologie, Institut de Recherche Expérimentale & Clinique and Department of Pneumology, Cliniques Universitaires St. Luc, Université Catholique de Louvain, Avenue Hippocrate 54, 1200 Brussels, Belgium;7. Laboratory of Pharmaceutical Technology, Department of Pharmaceutics, Ghent University, Harelbekestraat 72, 9000 Ghent, Belgium |
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| Abstract: | ![]()
Receptor mediated gene delivery is an attractive non-viral method for targeting genetic material to specific cell types. We have previously utilized oxidized (OMPLL) and reduced mannan poly-l-lysine (RMPLL) to target DNA vaccines to antigen presenting cells and demonstrated that it could induce far stronger immune responses in mice compared to naked DNA immunization. In this study, we describe the immune enhancing attributes of mannan-PLL mediated DNA vaccination at the molecular level. Several attributes observed in similar gene delivery conjugates, such as entry via the endocytic pathway, low toxicity, protection from nucleases and compaction of particle size, were also evident here. In addition, OMPLL and RMPLL conjugates had profound effects on the antigen presentation functions of dendritic cells and macrophages, through the stimulation of cytokine production and maturation of dendritic cells. Interestingly, we demonstrate that OMPLL–DNA and RMPLL–DNA are able to mediate dendritic cell activation via toll-like receptor 2 as opposed to mannan alone which mediates via toll-like receptor 4. Overall, this report leads to greater understanding of how oxidized and reduced mannan mediated gene delivery could augment immune responses to DNA vaccination and provide insights into ways of further improving its immunogenicity. |
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