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CVI Accepts, published online ahead of print on 28 February 2007
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Clin. Vaccine Immunol. doi:10.1128/CVI.00387-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Pre-clinical evaluation of microneedle technology for intradermal delivery of influenza vaccines

Jason B. Alarcon, Andrea Waterston Hartley, Noel G. Harvey, and John A. Mikszta*

BD Technologies, Research Triangle Park, NC, 27709

* To whom correspondence should be addressed. Email: john_mikszta{at}bd.com.


   Abstract

Recent clinical studies have suggested that, for certain strains of influenza virus, intradermal (ID) delivery may enable protective level immune responses using a lower dose of vaccine than required by intramuscular (IM) injection. Here, we describe the first pre-clinical use of microneedle technology for ID administration of three different types of influenza vaccines: a whole, inactivated influenza virus, a trivalent split virion human vaccine and a plasmid DNA encoding the influenza virus hemagglutinin. In a rat model, ID delivery of the whole inactivated virus provided up to 100-fold dose sparing compared to IM injection. In addition, ID delivery of the trivalent human vaccine enabled at least 10-fold dose sparing for the H1N1 strain and elicited similar levels of response across the dose range as IM injection for the H3N2 and B strains. Furthermore, at least 5-fold dose sparing from ID delivery was evident in animals treated with multiple doses of DNA plasmid vaccine, although such effects were not apparent after the first immunization. Altogether, the results demonstrate that microneedle-based ID delivery elicits antibody responses that are at least as strong as via IM injection and that, in many cases, dose sparing can be achieved by this new immunization method.







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