Ovalbumin-coated pH-sensitive microneedle arrays effectively induce ovalbumin-specific antibody and T-cell responses in mice

• Published in: European journal of pharmaceutics and biopharmaceutics Vol. 88; no. 2; pp. 310 - 315
• Main Authors: van der Maaden, Koen, Varypataki, Eleni Maria, Romeijn, Stefan, Ossendorp, Ferry, Jiskoot, Wim, Bouwstra, Joke
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2014
• Subjects: Animals; Antibodies - immunology; Antibody Formation; Dermal immunization; Female; Functional coatings; Humans; Hydrogen-Ion Concentration; In Vitro Techniques; Mice; Mice, Inbred BALB C; Microneedles; Minimally-invasive drug delivery; Needles; Ovalbumin - chemistry; Ovalbumin - immunology; pH-triggered delivery; T-Lymphocytes - immunology; Transdermal drug delivery; Transdermal drug delivery; Functional coatings; Dermal immunization; Microneedles; Minimally-invasive drug delivery; pH-triggered delivery
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2014.05.003

•Vaccine delivery via pH-sensitive microneedles is very efficient.•Vaccination via microneedles induces antigen-specific CD4+ and CD8+ T-cell responses.•Vaccination via pH-sensitive microneedles induces both T cell and B cell responses.•pH-sensitive microneedles are used for controlled intradermal vaccination. 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 7μg 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 100μg 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.