title: Ovalbumin-coated pH-sensitive microneedle arrays effectively induce ovalbumin-specific antibody and T-cell responses in mice.
abstract: The aim of this work was to study the applicability of antigen-coated pH-sensitive microneedle arrays for effective vaccination strategies. Therefore, a model antigen (ovalbumin) was coated onto pH-sensitive (pyridine-modified) microneedle arrays to test pH-triggered antigen release by applying the coated arrays onto ex vivo human skin, and by conducting a dermal immunization study in mice. The release of antigen into ex vivo human skin from the coated microneedles was determined by using radioactively labeled ovalbumin. To investigate the induction of antigen-specific IgG, and CD4(+) and CD8(+) T-cell responses, BALB/c mice were immunized with antigen-coated pH-sensitive microneedles by the 'coat and poke' approach. These responses were compared to responses induced by the 'poke and patch' approach, and subcutaneous and intradermal vaccination with classic hypodermic needles. The pH-sensitive microneedle arrays were efficiently coated with ovalbumin (95% coating efficiency) and upon application of six microneedle arrays 4.27 of 7 μg ovalbumin was delivered into the skin, showing a release efficiency of 70%. In contrast, the 'poke and patch' approach led to a delivery of only 6.91 of 100 μg ovalbumin (7% delivery efficiency). Immunization by means of ovalbumin-coated microneedles resulted in robust CD4(+) and CD8(+) T-cell responses comparable to those obtained after subcutaneous or intradermal immunization with conventional needles. Moreover, it effectively induced IgG responses; however, it required prime-boost immunizations before antibodies were produced. In conclusion, antigen delivery into ex vivo human skin by antigen-coated pH-sensitive microneedle arrays is more efficient than the 'poke-and-patch' approach and in vivo vaccination studies show the applicability of pH-sensitive microneedles for the induction of both T cell and B cell responses.
authors.affiliation: Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research (LACDR), Leiden University, Leiden, The Netherlands.
authors.forename: Koen
authors.initials: K
authors.lastname: van der Maaden
authors.affiliation: Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research (LACDR), Leiden University, Leiden, The Netherlands; Department of Immunohematology and Blood Transfusion, Leiden University Medical Center (LUMC), Leiden, The Netherlands.
authors.forename: Eleni Maria
authors.initials: EM
authors.lastname: Varypataki
authors.affiliation: Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research (LACDR), Leiden University, Leiden, The Netherlands.
authors.forename: Stefan
authors.initials: S
authors.lastname: Romeijn
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center (LUMC), Leiden, The Netherlands.
authors.forename: Ferry
authors.initials: F
authors.lastname: Ossendorp
authors.affiliation: Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research (LACDR), Leiden University, Leiden, The Netherlands.
authors.forename: Wim
authors.initials: W
authors.lastname: Jiskoot
authors.affiliation: Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research (LACDR), Leiden University, Leiden, The Netherlands. Electronic address: bouwstra@lacdr.leidenuniv.nl.
authors.forename: Joke
authors.initials: J
authors.lastname: Bouwstra
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology*; D000917:Antibody Formation; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D009339:Needles; D010047:Ovalbumin / Q000737:chemistry* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000906:Antibodies; D010047:Ovalbumin
keywords: Dermal immunization; Functional coatings; Microneedles; Minimally-invasive drug delivery; Transdermal drug delivery; pH-triggered delivery