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The osmotic stress response of split influenza vaccine particles in an acidic environment

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Abstract

Oral influenza vaccine provides an efficient means of preventing seasonal and pandemic disease. In this work, the stability of envelope-type split influenza vaccine particles in acidic environments has been investigated. Owing to the fact that hyper-osmotic stress can significantly affect lipid assembly of vaccine, osmotic stress-induced morphological change of split vaccine particles, in conjunction with structural change of antigenic proteins, was investigated by the use of stopped-flow light scattering (SFLS), intrinsic fluorescence, transmission electron microscopy (TEM), and hemagglutination assay. Split vaccine particles were found to exhibit a step-wise morphological change in response to osmotic stress due to double-layered wall structure. The presence of hyper-osmotic stress in acidic medium (0.3 osmolarity, pH 2.0) induced a significant level of membrane perturbation as measured by SFLS and TEM, imposing more damage to antigenic proteins on vaccine envelope than can be caused by pH-induced conformational change at acidic iso-osmotic condition. Further supports were provided by the intrinsic fluorescence and hemagglutinin activity measurements. Thus, hyper-osmotic stress becomes an important factor for determining stability of split vaccine particles in acidic medium. These results are useful in better understanding the destabilizing mechanism of split influenza vaccine particles in gastric environment and in designing oral influenza vaccine formulations.

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Acknowledgments

This study was conducted at the University of Alberta and the University of Cincinnati. Influenza vaccines used in this work were produced at the Georgia State University. This project was funded by a grant from the Bill & Melinda Gates Foundation through the Grand Challenges Exploration Initiative (C.D.M. and H.J.C.), and in part by NIH/NIAID grants AI093772 (S.M.K.), AI087782 (S.M.K.), and AI105170 (S.M.K). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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The authors declare no conflict of interest.

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Authors and Affiliations

  1. Nanotechnology Accelerator and Department of Chemical and Materials Engineering, National Institute for Nanotechnology, University of Alberta, Edmonton, AB, T6G 2M9, Canada

    Hyo-Jick Choi & Carlo D. Montemagno

  2. Animal and Plant Quarantine Agency, Anyang, Gyeonggi-do, 430-757, Korea

    Min-Chul Kim

  3. Center for Inflammation, Immunity and Infection and Department of Biology, Georgia State University, Atlanta, GA, 30303, USA

    Sang-Moo Kang

Authors
  1. Hyo-Jick Choi
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  2. Min-Chul Kim
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  3. Sang-Moo Kang
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  4. Carlo D. Montemagno
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Correspondence to Hyo-Jick Choi or Carlo D. Montemagno.

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Choi, HJ., Kim, MC., Kang, SM. et al. The osmotic stress response of split influenza vaccine particles in an acidic environment. Arch. Pharm. Res. 37, 1607–1616 (2014). https://doi.org/10.1007/s12272-013-0257-5

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  • DOI: https://doi.org/10.1007/s12272-013-0257-5

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