Archives of Pharmacal Research

, Volume 37, Issue 12, pp 1607–1616

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

Research Article


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.


Influenza vaccine Split vaccine particle Whole inactivated virus vaccine particle Osmotic stress Stopped-flow light scattering 

Supplementary material

12272_2013_257_MOESM1_ESM.pdf (93 kb)
Supplementary material 1 (PDF 93 kb)


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Copyright information

© The Pharmaceutical Society of Korea 2013

Authors and Affiliations

  1. 1.Nanotechnology Accelerator and Department of Chemical and Materials Engineering, National Institute for NanotechnologyUniversity of AlbertaEdmontonCanada
  2. 2.Animal and Plant Quarantine AgencyAnyangKorea
  3. 3.Center for Inflammation, Immunity and Infection and Department of BiologyGeorgia State UniversityAtlantaUSA

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