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Preparation and evaluation of a freeze-dried oral killed cholera vaccine formulation
University of Gothenburg, Sweden.ORCID iD: 0000-0001-6783-4622
2011 (English)In: European journal of pharmaceutics and biopharmaceutics, ISSN 0939-6411, E-ISSN 1873-3441, Vol. 79, no 3, p. 508-518Article in journal (Refereed) Published
Abstract [en]

Different oral liquid cholera vaccines have proved to be safe and effective, but their formulations present problems for use in low-income countries, since large package volumes have to be transported and cold chain maintenance is required. A solid state formulation would here be more advantageous, and consequently, the possibility to develop a dry cholera vaccine formulation by freeze-drying was investigated. The ability of sucrose, trehalose and mannitol to provide process stabilization during freeze-drying was tested on a formalin-killed whole-cell Vibrio cholerae model vaccine. A matrix of sucrose or trehalose prevented bacterial aggregation, preserved cell morphology and maintained practically completely the protective lipopolysaccharide (LPS) antigen on the cell surface and its reactivity with specific antibody in vitro. After reconstitution, this formulation also retained the capacity to elicit a strong serum and gut mucosal anti-LPS antibody response in orally immunized mice, as compared to the corresponding liquid vaccine formulation. The full preservation of the in vivo immunogenicity was also maintained when the internationally widely licensed oral cholera vaccine Dukoral™, which comprises a cocktail of inactivated V. cholerae together with cholera toxin B-subunit (CTB), was freeze-dried using sucrose for stabilization. Thus, we present a process generating a dry oral inactivated whole-cell cholera vaccine formulation with attractive features for public health use in cholera-afflicted settings.

Place, publisher, year, edition, pages
2011. Vol. 79, no 3, p. 508-518
Keywords [en]
Freeze-drying, Mannitol, Stabilization, Sucrose, Trehalose, Vibrio cholerae, bacterium lipopolysaccharide, cholera vaccine, immunoglobulin A, inactivated vaccine, animal experiment, antibody response, article, drug formulation, immunogenicity, immunoglobulin blood level, in vitro study, in vivo study, mouse, mucosal immunity, nonhuman, Administration, Oral, Animals, Antibodies, Bacterial, Calorimetry, Differential Scanning, Chemistry, Pharmaceutical, Cholera Toxin, Cholera Vaccines, Enzyme-Linked Immunosorbent Assay, Freeze Drying, Intestine, Small, Lipopolysaccharides, Mice, Mice, Inbred BALB C, Microscopy, Electron, Scanning, Surface Properties, Technology, Pharmaceutical, Vaccines, Inactivated, X-Ray Diffraction
National Category
Natural Sciences
Identifiers
URN: urn:nbn:se:ri:diva-56877DOI: 10.1016/j.ejpb.2011.06.009Scopus ID: 2-s2.0-80053982918OAI: oai:DiVA.org:ri-56877DiVA, id: diva2:1612587
Note

Funding details: Vetenskapsrådet, VR; Funding details: Marianne and Marcus Wallenberg Foundation, MMW; Funding text 1: The authors would like to thank Stefan Karlsson for assistance during the culturing and inactivation of the bacterial strains, Natascha Svensson for the preparation of purified O1 LPS and Bin-Ling Li and Annelie Ekman for technical assistance during the in vivo studies; all at the Department of Microbiology and Immunology, Göteborg University. We would also like to acknowledge the Centre for Cellular Imaging (CCI) at Sahlgrenska Academy, University of Gothenburg, for the use of imaging equipment and especially Maria Smedh for her help and support with the imaging of the bacteria samples. Further thanks to Anders Mårtensson for his help and technical assistance with the SEM image analyses and Richard Hejl for perfoming the XRD analysis; both at the Department of Chemical and Biological Engineering, Chalmers University of Technology. Financial support for this work was acquired from the Chalmers Bioscience Program funded by a strategic initiative of Chalmers University of Technology Foundation, the Swedish Research Council and the Marianne and Marcus Wallenberg Foundation.

Available from: 2021-11-18 Created: 2021-11-18 Last updated: 2023-03-14Bibliographically approved

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