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

<h4>Background</h4>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 wer...

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Autores principales:	Germain J P Fernando, Xianfeng Chen, Tarl W Prow, Michael L Crichton, Emily J Fairmaid, Michael S Roberts, Ian H Frazer, Lorena E Brown, Mark A F Kendall
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/513f0894b14147b3946ebd930b55e4f0
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spelling	oai:doaj.org-article:513f0894b14147b3946ebd930b55e4f02021-11-25T06:24:25ZPotent immunity to low doses of influenza vaccine by probabilistic guided micro-targeted skin delivery in a mouse model.1932-620310.1371/journal.pone.0010266https://doaj.org/article/513f0894b14147b3946ebd930b55e4f02010-04-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20422002/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>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.Germain J P FernandoXianfeng ChenTarl W ProwMichael L CrichtonEmily J FairmaidMichael S RobertsIan H FrazerLorena E BrownMark A F KendallPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 4, p e10266 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Germain J P Fernando Xianfeng Chen Tarl W Prow Michael L Crichton Emily J Fairmaid Michael S Roberts Ian H Frazer Lorena E Brown Mark A F Kendall Potent immunity to low doses of influenza vaccine by probabilistic guided micro-targeted skin delivery in a mouse model.
description	<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>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.
format	article
author	Germain J P Fernando Xianfeng Chen Tarl W Prow Michael L Crichton Emily J Fairmaid Michael S Roberts Ian H Frazer Lorena E Brown Mark A F Kendall
author_facet	Germain J P Fernando Xianfeng Chen Tarl W Prow Michael L Crichton Emily J Fairmaid Michael S Roberts Ian H Frazer Lorena E Brown Mark A F Kendall
author_sort	Germain J P Fernando
title	Potent immunity to low doses of influenza vaccine by probabilistic guided micro-targeted skin delivery in a mouse model.
title_short	Potent immunity to low doses of influenza vaccine by probabilistic guided micro-targeted skin delivery in a mouse model.
title_full	Potent immunity to low doses of influenza vaccine by probabilistic guided micro-targeted skin delivery in a mouse model.
title_fullStr	Potent immunity to low doses of influenza vaccine by probabilistic guided micro-targeted skin delivery in a mouse model.
title_full_unstemmed	Potent immunity to low doses of influenza vaccine by probabilistic guided micro-targeted skin delivery in a mouse model.
title_sort	potent immunity to low doses of influenza vaccine by probabilistic guided micro-targeted skin delivery in a mouse model.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/513f0894b14147b3946ebd930b55e4f0
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Potent immunity to low doses of influenza vaccine by probabilistic guided micro-targeted skin delivery in a mouse model.

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