Improved storage stability and immunogenicity of hepatitis B vaccine after spray-freeze drying in presence of sugars

W.F. Tonnis, J.-P. Amorij, M.A. Vreeman, H.W. Frijlink, G.F. Kersten, W.L.J. Hinrichs

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The current hepatitis B vaccines need to be stored and transported under refrigerated conditions (2-8 degrees C). This dependence on a cold-chain is highly challenging in areas where hepatitis B virus infections are endemic. To decrease the cold-chain dependency, powder formulations of the hepatitis B surface antigen (HBsAg) without aluminum were prepared by spray-freeze drying in the presence of either inulin or a combination of dextran and trehalose. The stability of HBsAg in the amorphous powder formulations was strongly improved during storage both at room temperature and at an elevated temperature (60 degrees C), compared to a liquid plain and an aluminum hydroxide adjuvanted HBsAg formulation. Immunogenicity studies in mice showed that reconstituted powder formulations induced higher IgG immune responses after intramuscular administration than those induced after administration of unprocessed plain antigen. Although the immune response was not as high as after administration of aluminum adjuvanted liBsAg, the immune response to the reconstituted vaccines shifted towards a more balanced Thl/Th2 response compared to the aluminum containing HBsAg formulation. (C) 2014 Elsevier B.V. All rights reserved.

Original languageEnglish
Pages (from-to)36-45
Number of pages10
JournalEuropean Journal Pharmaceutical Sciences
Issue number1
Publication statusPublished - 13-May-2014


  • Dextran
  • Hepatitis B surface antigen
  • Inulin
  • Powder formulation
  • Stabilization
  • Trehalose
  • aluminum
  • aluminum hydroxide
  • dextran
  • hepatitis B surface antigen
  • immunoglobulin G
  • inulin
  • trehalose
  • animal experiment
  • animal model
  • article
  • controlled study
  • drug formulation
  • drug stability
  • drug storage
  • enzyme linked immunosorbent assay
  • female
  • fluorescence spectroscopy
  • freeze drying
  • freeze thawing
  • hepatitis B
  • immune response
  • immunogenicity
  • infant
  • moisture
  • mouse
  • nonhuman
  • powder
  • priority journal
  • room temperature
  • scanning electron microscopy
  • spray drying
  • temperature
  • water content
  • X ray powder diffraction

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