title: Coated microneedle arrays for transcutaneous delivery of live virus vaccines.
abstract: Vaccines are sensitive biologics that require continuous refrigerated storage to maintain their viability. The vast majority of vaccines are also administered using needles and syringes. The need for cold chain storage and the significant logistics surrounding needle-and-syringe vaccination is constraining the success of immunization programs. Recombinant live viral vectors are a promising platform for the development of vaccines against a number of infectious diseases, however these viruses must retain infectivity to be effective. Microneedles offer an effective and painless method for delivery of vaccines directly into skin that in the future could provide solutions to current vaccination issues. Here we investigated methods of coating live recombinant adenovirus and modified vaccinia virus Ankara (MVA) vectors onto solid microneedle arrays. An effective spray-coating method, using conventional pharmaceutical processes, was developed, in tandem with suitable sugar-based formulations, which produces arrays with a unique coating of viable virus in a dry form around the shaft of each microneedle on the array. Administration of live virus-coated microneedle arrays successfully resulted in virus delivery, transcutaneous infection and induced an antibody or CD8(+) T cell response in mice that was comparable to that obtained by needle-and-syringe intradermal immunization. To our knowledge, this is the first report of successful vaccination with recombinant live viral vectored vaccines coated on microneedle delivery devices.
authors.affiliation: School of Pharmacy, University College Cork, Cork, Ireland. avrdoljak@gmail.com
authors.forename: Anto
authors.initials: A
authors.lastname: Vrdoljak
authors.forename: Marie G
authors.initials: MG
authors.lastname: McGrath
authors.forename: John B
authors.initials: JB
authors.lastname: Carey
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Draper
authors.forename: Adrian V S
authors.initials: AV
authors.lastname: Hill
authors.forename: Conor
authors.initials: C
authors.lastname: O'Mahony
authors.forename: Abina M
authors.initials: AM
authors.lastname: Crean
authors.forename: Anne C
authors.initials: AC
authors.lastname: Moore
mesh_terms: D000256:Adenoviridae / Q000276:immunology; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D007114:Immunization / Q000295:instrumentation / Q000379:methods*; D007271:Injections, Intradermal; D051379:Mice; D008810:Mice, Inbred C57BL; D008845:Microinjections; D009339:Needles; D012825:Silicon; D012867:Skin; D013552:Swine; D014613:Vaccines, Attenuated / Q000008:administration & dosage*; D014616:Vaccinia virus / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage*
chemical_list: D000914:Antibodies, Viral; D014613:Vaccines, Attenuated; D014765:Viral Vaccines; D012825:Silicon