title: Dissolving microneedle delivery of nanoparticle-encapsulated antigen elicits efficient cross-priming and Th1 immune responses by murine Langerhans cells.
abstract: Dendritic cells (DCs) of the skin have an important role in skin-mediated immunity capable of promoting potent immune responses. We availed of polymeric dissolving microneedle (MN) arrays laden with nano-encapsulated antigen to specifically target skin DC networks. This modality of immunization represents an economic, efficient, and potent means of antigen delivery directly to skin DCs, which are inefficiently targeted by more conventional immunization routes. Following MN immunization, Langerhans cells (LCs) constituted the major skin DC subset capable of cross-priming antigen-specific CD8+ T cells ex vivo. Although all DC subsets were equally efficient in priming CD4+ T cells, LCs were largely responsible for orchestrating the differentiation of CD4+ IFN-γ- and IL-17-producing effectors. Importantly, depletion of LCs prior to immunization had a profound effect on CD8+ CTL responses in vivo, and vaccinated animals displayed reduced protective anti-tumor and viral immunity. Interestingly, this cross-priming bias was lost following MN immunization with soluble antigen, suggesting that processing and cross-presentation of nano-particulate antigen is favored by LCs. Therefore, these studies highlight the importance of LCs in skin immunization strategies and that targeting of nano-particulate immunogens through dissolvable polymeric MNs potentially provides a promising technological platform for improved vaccination strategies.
authors.affiliation: The Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, UK.
authors.forename: Marija
authors.initials: M
authors.lastname: Zaric
authors.affiliation: The Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, UK.
authors.forename: Oksana
authors.initials: O
authors.lastname: Lyubomska
authors.affiliation: The Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, UK.
authors.forename: Candice
authors.initials: C
authors.lastname: Poux
authors.affiliation: The Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, UK.
authors.forename: Mary L
authors.initials: ML
authors.lastname: Hanna
authors.affiliation: School of Pharmacy, Queen's University Belfast, Belfast, UK.
authors.forename: Maeliosa T
authors.initials: MT
authors.lastname: McCrudden
authors.affiliation: Centre d'Immunologie de Marseille-Luminy (CIML), Aix Marseille Université, Marseille, France; INSERM U1104, Marseille, France; CNRS UMR7280, Marseille, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Malissen
authors.affiliation: The Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, UK.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Ingram
authors.affiliation: The Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, UK.
authors.forename: Ultan F
authors.initials: UF
authors.lastname: Power
authors.affiliation: School of Pharmacy, Queen's University Belfast, Belfast, UK.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Scott
authors.affiliation: School of Pharmacy, Queen's University Belfast, Belfast, UK.
authors.forename: Ryan F
authors.initials: RF
authors.lastname: Donnelly
authors.affiliation: The Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, UK. Electronic address: a.kissenpfennig@qub.ac.uk.
authors.forename: Adrien
authors.initials: A
authors.lastname: Kissenpfennig
mesh_terms: D000818:Animals; D000941:Antigens / Q000008:administration & dosage*; D000954:Antigens, Surface / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045142:Cross-Priming / Q000276:immunology*; D007114:Immunization; D007801:Langerhans Cells / Q000276:immunology*; D037181:Lectins, C-Type / Q000032:analysis; D037241:Mannose-Binding Lectins / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles; D010047:Ovalbumin / Q000276:immunology; D029082:Sendai virus / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology
chemical_list: D000941:Antigens; D000954:Antigens, Surface; C498497:Cd207 protein, mouse; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D010047:Ovalbumin