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Potent immunity to low doses of influenza vaccine by probabilistic guided micro-targeted skin delivery in a mouse model

Fernando, Germain J P ; Chen, Xianfeng ; Prow, Tarl W ; Crichton, Michael L ; Fairmaid, Emily J ; Roberts, Michael S ; Frazer, Ian H ; Brown, Lorena E ; Kendall, Mark A F Fooks, Anthony R.

PloS one, 2010-04, Vol.5 (4), p.e10266-e10266 [Periódico revisado por pares]

United States: Public Library of Science

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Título:
Potent immunity to low doses of influenza vaccine by probabilistic guided micro-targeted skin delivery in a mouse model
Autor: Fernando, Germain J P ; Chen, Xianfeng ; Prow, Tarl W ; Crichton, Michael L ; Fairmaid, Emily J ; Roberts, Michael S ; Frazer, Ian H ; Brown, Lorena E ; Kendall, Mark A F
Fooks, Anthony R.
Assuntos: Analysis ; Animals ; Antigen-presenting cells ; Antigen-Presenting Cells - immunology ; Antigens ; Bioengineering ; Biomedical materials ; Biotechnology ; Communicable diseases ; Drug delivery systems ; Drug dosages ; Eye ; Genes ; Hepatitis ; Immune response ; Immune system ; Immunity ; Immunity, Humoral ; Immunology ; Immunology/Immune Response ; Immunotherapy ; Infectious diseases ; Influenza ; Influenza vaccines ; Influenza Vaccines - administration & dosage ; Influenza Vaccines - immunology ; Influenza viruses ; Injections ; Injections, Subcutaneous - methods ; Metabolism ; Mice ; Microinjections - methods ; Models, Animal ; Nanotechnology ; Pandemics ; Pathogens ; Polymerization ; Probability ; Public Health and Epidemiology/Immunization ; Sharpness ; Shortages ; Skin ; Skin - immunology ; Statistical analysis ; Tapering ; Theoretical analysis ; Tips ; Treatment Outcome ; Vaccination ; Vaccines ; Virology/Vaccines ; Viruses
É parte de: PloS one, 2010-04, Vol.5 (4), p.e10266-e10266
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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Conceived and designed the experiments: GJF XC TWP MSR IHF LEB MAK. Performed the experiments: GJF XC TWP MLC EJF. Analyzed the data: GJF XC TWP MLC EJF IHF LEB MAK. Contributed reagents/materials/analysis tools: GJF XC TWP MLC EJF MSR IHF LEB MAK. Wrote the paper: GJF XC TWP MLC MSR LEB MAK.
Descrição: Over 14 million people die each year from infectious diseases despite extensive vaccine use [1]. The needle and syringe--first invented in 1853--is still the primary delivery device, injecting liquid vaccine into muscle. Vaccines could be far more effective if they were precisely delivered into the narrow layer just beneath the skin surface that contains a much higher density of potent antigen-presenting cells (APCs) essential to generate a protective immune response. We hypothesized that successful vaccination could be achieved this way with far lower antigen doses than required by the needle and syringe. To meet this objective, using a probability-based theoretical analysis for targeting skin APCs, we designed the Nanopatch, which contains an array of densely packed projections (21025/cm(2)) invisible to the human eye (110 microm in length, tapering to tips with a sharpness of <1000 nm), that are dry-coated with vaccine and applied to the skin for two minutes. Here we show that the Nanopatches deliver a seasonal influenza vaccine (Fluvax 2008) to directly contact thousands of APCs, in excellent agreement with theoretical prediction. By physically targeting vaccine directly to these cells we induced protective levels of functional antibody responses in mice and also protection against an influenza virus challenge that are comparable to the vaccine delivered intramuscularly with the needle and syringe--but with less than 1/100(th) of the delivered antigen. Our results represent a marked improvement--an order of magnitude greater than reported by others--for injected doses administered by other delivery methods, without reliance on an added adjuvant, and with only a single vaccination. This study provides a proven mathematical/engineering delivery device template for extension into human studies--and we speculate that successful translation of these findings into humans could uniquely assist with problems of vaccine shortages and distribution--together with alleviating fear of the needle and the need for trained practitioners to administer vaccine, e.g., during an influenza pandemic.
Editor: United States: Public Library of Science
Idioma: Inglês

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Potent immunity to low doses of influenza vaccine by probabilistic guided micro-targeted skin delivery in a mouse model

Fernando, Germain J P ; Chen, Xianfeng ; Prow, Tarl W ; Crichton, Michael L ; Fairmaid, Emily J ; Roberts, Michael S ; Frazer, Ian H ; Brown, Lorena E ; Kendall, Mark A F Fooks, Anthony R.

United States: Public Library of Science

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