title: Nanoparticle-based targeting of vaccine compounds to skin antigen-presenting cells by hair follicles and their transport in mice.
abstract: Particle-based drug delivery systems target active compounds to the hair follicle and may result in a better penetration and higher efficiency of compound uptake by skin resident cells. As previously proposed, such delivery systems could be important tools for vaccine delivery. In this study, we investigated the penetration of solid fluorescent 40 or 200 nm polystyrene nanoparticles (NPs) as well as virus particles in murine skin to further investigate the efficacy of transcutaneously (TC) applied particulate vaccine delivery route. We demonstrated that 40 and 200 nm NPs and modified vaccinia Ankara (MVA) expressing the green-fluorescent protein penetrated deeply into hair follicles and were internalized by perifollicular antigen-presenting cells (APCs). Fibered-based confocal microscopy analyses allowed visualizing in vivo particle penetration along the follicular duct, diffusion into the surrounding tissue, uptake by APCs and transport to the draining lymph nodes. The application of small particles, such as ovalbumin coding DNA or MVA, induced both humoral and cellular immune responses. Furthermore, TC applied MVA induced protection against vaccinia virus challenge. Our results strengthen the concept of TC targeting of cutaneous APCs by hair follicles and will contribute to the development of advanced vaccination protocols using NPs or viral vectors.
authors.affiliation: Laboratoire d'Immunologie Cellulaire, INSERM U543, Université Pierre et Marie Curie-Paris6, Paris, France.
authors.forename: Brice
authors.initials: B
authors.lastname: Mahe
authors.forename: Annika
authors.initials: A
authors.lastname: Vogt
authors.forename: Christelle
authors.initials: C
authors.lastname: Liard
authors.forename: Darragh
authors.initials: D
authors.lastname: Duffy
authors.forename: Valérie
authors.initials: V
authors.lastname: Abadie
authors.forename: Olivia
authors.initials: O
authors.lastname: Bonduelle
authors.forename: Alexandre
authors.initials: A
authors.lastname: Boissonnas
authors.forename: Wolfram
authors.initials: W
authors.lastname: Sterry
authors.forename: Bernard
authors.initials: B
authors.lastname: Verrier
authors.forename: Ulrike
authors.initials: U
authors.lastname: Blume-Peytavi
authors.forename: Behazine
authors.initials: B
authors.lastname: Combadiere
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000914:Antibodies, Viral / Q000378:metabolism; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000378:metabolism*; D001692:Biological Transport / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D049452:Green Fluorescent Proteins / Q000378:metabolism; D018859:Hair Follicle / Q000166:cytology / Q000378:metabolism*; D007801:Langerhans Cells / Q000166:cytology / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D049329:Nanostructures / Q000008:administration & dosage*; D036103:Nanotechnology / Q000379:methods; D011137:Polystyrenes / Q000378:metabolism; D014612:Vaccines / Q000008:administration & dosage*; D014615:Vaccinia / Q000276:immunology / Q000378:metabolism*; D014777:Virus Diseases / Q000276:immunology / Q000517:prevention & control
chemical_list: D000914:Antibodies, Viral; D011137:Polystyrenes; D014612:Vaccines; D049452:Green Fluorescent Proteins