title: Mannosylation of virus-like particles enhances internalization by antigen presenting cells.
abstract: Internalization of peptides by antigen presenting cells is crucial for the initiation of the adaptive immune response. Mannosylation has been demonstrated to enhance antigen uptake through mannose receptors, leading to improved immune responses. In this study we test the effect of surface mannosylation of protein-based virus-like particles (VLP) derived from Rabbit hemorrhagic disease virus (RHDV) on uptake by murine and human antigen presenting cells. A monomannoside and a novel dimannoside were synthesized and successfully conjugated to RHDV VLP capsid protein, providing approximately 270 mannose groups on the surface of each virus particle. VLP conjugated to the mannoside or dimannoside exhibited significantly enhanced binding and internalization by murine dendritic cells, macrophages and B cells as well as human dendritic cells and macrophages. This uptake was inhibited by the inclusion of mannan as a specific inhibitor of mannose specific uptake, demonstrating that mannosylation of VLP targets mannose receptor-based uptake. Consistent with mannose receptor-based uptake, partial retargeting of the intracellular processing of RHDV VLP was observed, confirming that mannosylation of VLP provides both enhanced uptake and modified processing of associated antigens.
authors.affiliation: Department of Microbiology and Immunology, Otago School of Medical Science, University of Otago, Dunedin, New Zealand.
authors.forename: Farah
authors.initials: F
authors.lastname: Al-Barwani
authors.affiliation: Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Young
authors.affiliation: Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Baird
authors.affiliation: Department of Chemistry, Division of Sciences, University of Otago, Dunedin, New Zealand.
authors.forename: David S
authors.initials: DS
authors.lastname: Larsen
authors.affiliation: Department of Microbiology and Immunology, Otago School of Medical Science, University of Otago, Dunedin, New Zealand.
authors.forename: Vernon K
authors.initials: VK
authors.lastname: Ward
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000941:Antigens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D017929:Hemorrhagic Disease Virus, Rabbit / Q000276:immunology; D006801:Humans; D037181:Lectins, C-Type / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008358:Mannose / Q000276:immunology*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000276:immunology
chemical_list: D000941:Antigens; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D008358:Mannose