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Stability Kinetics of Influenza Vaccine Coated onto Microneedles During Drying and Storage

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ABSTRACT

Purpose

This study sought to determine the effects of microneedle coating formulation, drying time and storage time on antigen stability and in vivo immunogenicity of influenza microneedle vaccines.

Methods

The stability of inactivated influenza virus vaccine was monitored by hemagglutination (HA) activity and virus particle aggregation as a function of storage time and temperature with or without trehalose. In vivo immunogenicity of inactivated influenza vaccines coated onto microneedles was determined in mice by virus-specific antibody titers and survival rates.

Results

In the absence of trehalose, HA activity decreased below 10% and to almost zero after 1 h and 1 month of drying, respectively. Addition of trehalose maintained HA activity above 60% after drying and above 20% after 1 month storage at 25°C. Loss of HA activity generally correlated with increased virus particle aggregation. Administration of microneedles coated with trehalose-stabilized influenza vaccine yielded high serum IgG antibody titers even after 1 month storage, and all animals survived with minimal weight loss after lethal challenge infection.

Conclusions

Inactivated influenza virus vaccine coated on microneedles with trehalose significantly improved the HA activity as well as in vivo immunogenicity of the vaccine after an extended time of storage.

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ACKNOWLEDGMENTS

This work was carried out at the Emory University School of Medicine and the Georgia Tech Center for Drug Design, Development and Delivery and Institute for Bioengineering and Biosciences. It was supported in part by NIH grants R01-EB006369 (M.R.P.), U01-AI0680003 (R.W.C.), SERCEB (R.W.C) and the Georgia Research Alliance Program grant (S.M.K). We thank Dr. Vladimir Zarnitsyn for microneedle fabrication, Dr. Andrew Lyon for dynamic light scattering assay, and Dr. Mark Allen for laser microfabrication facilities. M.R.P. serves as a consultant and is an inventor on patents licensed to companies developing microneedle-based products. This possible conflict of interest has been disclosed and is being managed by Georgia Tech and Emory University.

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Authors and Affiliations

  1. School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, Georgia, 30332, USA

    Yeu-Chun Kim & Mark R. Prausnitz

  2. Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, 30322, USA

    Fu-Shi Quan, Richard W. Compans & Sang-Moo Kang

Authors
  1. Yeu-Chun Kim
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  2. Fu-Shi Quan
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  3. Richard W. Compans
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  4. Sang-Moo Kang
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  5. Mark R. Prausnitz
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Corresponding authors

Correspondence to Sang-Moo Kang or Mark R. Prausnitz.

Additional information

Yeu-Chun Kim and Fu-Shi Quan contributed equally to this work.

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Kim, YC., Quan, FS., Compans, R.W. et al. Stability Kinetics of Influenza Vaccine Coated onto Microneedles During Drying and Storage. Pharm Res 28, 135–144 (2011). https://doi.org/10.1007/s11095-010-0134-6

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  • DOI: https://doi.org/10.1007/s11095-010-0134-6

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