Formulation and coating of microneedles with inactivated influenza virus to improve vaccine stability and immunogenicity

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Microneedle patches coated with solid-state influenza vaccine have been developed to improve vaccine efficacy and patient coverage. However, dip coating microneedles with influenza vaccine can reduce antigen activity. In this study, we sought to determine the experimental factors and mechanistic pathways by which inactivated influenza vaccine can lose activity, as well as develop and assess improved microneedle coating formulations that protect the antigen from activity loss. After coating microneedles using a standard vaccine formulation, the stability of influenza vaccine was reduced to just 2%, as measured by hemagglutination activity. The presence of carboxymethylcellulose, which was added to increase viscosity of the coating formulation, was shown to contribute to vaccine activity loss. After screening a panel of candidate stabilizers, the addition of trehalose to the coating formulation was found to protect the antigen and retain 48-82% antigen activity for all three major strains of seasonal influenza: H1N1, H3N2 and B. Influenza vaccine coated in this way also exhibited thermal stability, such that activity loss was independent of temperature over the range of 4-37 degrees C for 24 h. Dynamic light scattering measurements showed that antigen activity loss was associated with virus particle aggregation, and that stabilization using trehalose largely blocked this aggregation. Finally, microneedles using an optimized vaccine coating formulation were applied to the skin to vaccinate mice. Microneedle vaccination induced robust systemic and functional antibodies and provided complete protection against lethal challenge infection similar to conventional intramuscular injection. Overall, these results show that antigen activity loss during microneedle coating can be largely prevented through optimized formulation and that stabilized microneedle patches can be used for effective vaccination. (C) 2009 Elsevier B.V. All rights reserved.
Publisher
ELSEVIER SCIENCE BV
Issue Date
2010-03
Language
English
Article Type
Article
Keywords

TRANSCUTANEOUS IMMUNIZATION; PANDEMIC INFLUENZA; SUGAR GLASSES; IN-VIVO; DELIVERY; SKIN; STABILIZATION; CHALLENGE; PATCH; HEMAGGLUTININ

Citation

JOURNAL OF CONTROLLED RELEASE, v.142, no.2, pp.187 - 195

ISSN
0168-3659
DOI
10.1016/j.jconrel.2009.10.013
URI
http://hdl.handle.net/10203/101969
Appears in Collection
CBE-Journal Papers(저널논문)
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