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Enhanced Stability of Inactivated Influenza Vaccine Encapsulated in Dissolving Microneedle Patches

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Abstract

Purpose

This study tested the hypothesis that encapsulation of influenza vaccine in microneedle patches increases vaccine stability during storage at elevated temperature.

Methods

Whole inactivated influenza virus vaccine (A/Puerto Rico/8/34) was formulated into dissolving microneedle patches and vaccine stability was evaluated by in vitro and in vivo assays of antigenicity and immunogenicity after storage for up to 3 months at 4, 25, 37 and 45°C.

Results

While liquid vaccine completely lost potency as determined by hemagglutination (HA) activity within 1–2 weeks outside of refrigeration, vaccine in microneedle patches lost 40–50% HA activity during or shortly after fabrication, but then had no significant additional loss of activity over 3 months of storage, independent of temperature. This level of stability required reduced humidity by packaging with desiccant, but was not affected by presence of oxygen. This finding was consistent with additional stability assays, including antigenicity of the vaccine measured by ELISA, virus particle morphological structure captured by transmission electron microscopy and protective immune responses by immunization of mice in vivo.

Conclusions

These data show that inactivated influenza vaccine encapsulated in dissolving microneedle patches has enhanced stability during extended storage at elevated temperatures.

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Abbreviations

HA:

Hemagglutination

HRP:

Horseradish peroxidase

IACUC:

Institutional animal care and use committee

OD:

Optical density

PBS:

Phosphate-buffered saline

PBST:

Phosphate-buffered saline plus 0.5% Tween-20

PDMS:

Polydimethylsiloxane

PVA:

Polyvinyl alcohol

RBC:

Red blood cell

s.d.:

Standard deviation

TMB:

Tetramethylbenzidine

TEM:

Transmission electron microscopy

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ACKNOWLEDGMENTS AND DISCLOSURES

We would like to thank Seong-O Choi for providing the pyramidal microneedle master structure and Donna Bondy for administrative support. This work was supported in part by the National Institutes of Health. The work was carried out at the Center for Drug Design, Development and Delivery and the Institute for Bioengineering and Bioscience at the Georgia Institute of Technology, and at the Emory Vaccine Center. Mark Prausnitz is an inventor on patents and has a significant financial interest in a company that is developing microneedle-based products (Micron Biomedical). This potential conflict of interest has been disclosed and is being managed by Georgia Tech and Emory University.

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Authors and Affiliations

  1. Wallace H. Coulter Department of Biomedical Engineering, Georgia Technology and Emory University, Georgia Institute of Technology, Atlanta, Georgia, 30332, USA

    Leonard Y. Chu & Mark R. Prausnitz

  2. Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, 30329, USA

    Ling Ye, Ke Dong, Richard W. Compans & Chinglai Yang

  3. School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, 311 Ferst Drive, Atlanta, Georgia, 30332, USA

    Mark R. Prausnitz

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  1. Leonard Y. Chu
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  2. Ling Ye
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  3. Ke Dong
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  4. Richard W. Compans
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  6. Mark R. Prausnitz
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Correspondence to Mark R. Prausnitz.

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Chu, L.Y., Ye, L., Dong, K. et al. Enhanced Stability of Inactivated Influenza Vaccine Encapsulated in Dissolving Microneedle Patches. Pharm Res 33, 868–878 (2016). https://doi.org/10.1007/s11095-015-1833-9

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  • DOI: https://doi.org/10.1007/s11095-015-1833-9

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