title: Particle-based transcutaneous administration of HIV-1 p24 protein to human skin explants and targeting of epidermal antigen presenting cells.
abstract: Transcutaneous immunization is a promising vaccination strategy for the treatment of infectious diseases and cancer. In this study, we investigate the combination of cyanoacrylate skin surface stripping (CSSS) and particle-based antigen delivery to target the HIV-1 p24 protein to skin antigen presenting cells (APC). The CSSS treatment pre-activates skin APC and opens hair follicles, where protein-loaded particles accumulate and allow for sustained delivery of the loaded antigen to perifollicular APC. We found that poly-lactic acid (PLA) and polystyrene (PS) particles targeted the adsorbed HIV-1 p24 protein to the hair follicles. Small amounts of PS and PLA particles were found to translocate to the epidermis and be internalized by skin cells, whereas most of the particles aggregated in the hair follicle canal, where they released the loaded antigen. The p24 protein diffused to the epidermis and dermis and was detected in skin cells, especially in Langerhans cells and dermal dendritic cells. Furthermore, the combination of CSSS and particle-based delivery resulted in activation and maturation of Langerhans cells (HLA-DR, CD80 and CD83). We conclude that particle-based antigen delivery across partially disrupted skin barrier is a feasible and effective approach to needle-free transcutaneous vaccination.
authors.affiliation: Clinical Research Center for Hair and Skin Science, Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Berlin, Germany. Electronic address: fiorenza.rancan@charite.de.
authors.forename: Fiorenza
authors.initials: F
authors.lastname: Rancan
authors.affiliation: Clinical Research Center for Hair and Skin Science, Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Amselgruber
authors.affiliation: Clinical Research Center for Hair and Skin Science, Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Hadam
authors.affiliation: Institut de Biologie et Chimie des Protéines UMR 5305, CNRS/Université de Lyon, France.
authors.forename: Sevérine
authors.initials: S
authors.lastname: Munier
authors.affiliation: Institut de Biologie et Chimie des Protéines UMR 5305, CNRS/Université de Lyon, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Pavot
authors.affiliation: Institut de Biologie et Chimie des Protéines UMR 5305, CNRS/Université de Lyon, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Verrier
authors.affiliation: Department of Physics, Humboldt Universität Berlin, Berlin, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Hackbarth
authors.affiliation: Laboratory of Immunity and Infection, Université Pierre et Marie Curie (UPMC University Paris 06), Paris Cedex 13, France.
authors.forename: Behazine
authors.initials: B
authors.lastname: Combadiere
authors.affiliation: Clinical Research Center for Hair and Skin Science, Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Blume-Peytavi
authors.affiliation: Clinical Research Center for Hair and Skin Science, Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Annika
authors.initials: A
authors.lastname: Vogt
mesh_terms: D000279:Administration, Cutaneous; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism*; D003487:Cyanoacrylates / Q000494:pharmacology; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D016655:HIV Core Protein p24 / Q000008:administration & dosage* / Q000737:chemistry; D018859:Hair Follicle / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D019344:Lactic Acid / Q000737:chemistry*; D011091:Polyesters; D011108:Polymers / Q000737:chemistry*; D011137:Polystyrenes / Q000737:chemistry*; D012867:Skin / Q000276:immunology / Q000378:metabolism*
chemical_list: D003487:Cyanoacrylates; D004337:Drug Carriers; D016655:HIV Core Protein p24; D011091:Polyesters; D011108:Polymers; D011137:Polystyrenes; C514799:p24 protein, Human Immunodeficiency Virus Type 1; D019344:Lactic Acid; C033616:poly(lactide)
keywords: Cyanoacrylate stripping; DC activation; Langerhans cells; Poly-lactic acid; Transcutaneous vaccination