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. and Kendall, Mark A. F. (2010) Potent immunity to low doses of influenza vaccine by probabilistic guided micro-targeted skin delivery in a mouse model. PLoS One, 5 4: e10266.1-e10266.11. doi:10.1371/journal.pone.0010266

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Author 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.
Title Potent immunity to low doses of influenza vaccine by probabilistic guided micro-targeted skin delivery in a mouse model
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2010
Sub-type Article (original research)
DOI 10.1371/journal.pone.0010266
Open Access Status DOI
Volume 5
Issue 4
Start page e10266.1
End page e10266.11
Total pages 11
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Collection year 2011
Language eng
Subject 1107 Immunology
Formatted abstract
Background: Over 14 million people die each year from infectious diseases despite extensive vaccine use. 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.

Methodology/Principal Findings: 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/cm2) invisible to the human eye (110 µm 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 1/100th of the delivered antigen.

Conclusions/Significance: 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.

Keyword Epidermal langerhans cells
Coated microneedle arrays
Pandemic influenza
Dendritic cells
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article # e10266

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Created: Sun, 09 May 2010, 00:01:21 EST