Preparation and evaluation of a freeze-dried oral killed cholera vaccine formulation
Journal article, 2011
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 (TM), 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.
Cholera Vaccines
Sucrose
Microscopy
Mice
chemistry
risk
field trial
chemistry
immunology
Differential Scanning
Oral
immunology
immunization
Inbred BALB C
toxin b-subunit
Animals
immunology
vibrio-cholerae
immunology
Vibrio
Immunoglobulin A
bangladesh
Freeze-drying
antibodies
Surface Properties
blood
administration & dosage
Mannitol
Mice
Vaccines
Scanning
biosynthesis
Calorimetry
Freeze Drying
Cholera Toxin
Lipopolysaccharides
immunology
Vibrio cholerae
biosynthesis
administration & dosage
immunology
Small
Bacterial
X-Ray Diffraction
Antibodies
Enzyme-Linked Immunosorbent Assay
Technology
Intestine
Administration
membranes
escherichia-coli
Inactivated
Stabilization
Chemistry
Pharmaceutical
Pharmaceutical
Electron
blood
cholerae
Trehalose
Author
Annika Borde
SuMo Biomaterials
Chalmers, Chemical and Biological Engineering, Pharmaceutical Technology
Anette Larsson
SuMo Biomaterials
Chalmers, Chemical and Biological Engineering, Pharmaceutical Technology
Jan Holmgren
University of Gothenburg
Erik Nygren
University of Gothenburg
European Journal of Pharmaceutics and Biopharmaceutics
0939-6411 (ISSN)
Vol. 79 3 508-518Subject Categories (SSIF 2011)
Pharmaceutical Sciences
Microbiology in the medical area
Chemical Sciences
Areas of Advance
Materials Science
DOI
10.1016/j.ejpb.2011.06.009
PubMed
21757004