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.
cholerae
field trial
Trehalose
Mice
Small
toxin b-subunit
risk
Cholera Toxin
immunology
chemistry
Calorimetry
Mannitol
administration & dosage
chemistry
Vaccines
blood
Bacterial
Administration
antibodies
immunology
membranes
immunization
biosynthesis
immunology
Intestine
Microscopy
Lipopolysaccharides
immunology
escherichia-coli
Vibrio cholerae
Mice
Differential Scanning
Electron
Cholera Vaccines
X-Ray Diffraction
immunology
Scanning
immunology
Animals
Stabilization
Inbred BALB C
administration & dosage
biosynthesis
Oral
Enzyme-Linked Immunosorbent Assay
Pharmaceutical
Freeze-drying
Sucrose
bangladesh
Surface Properties
Technology
vibrio-cholerae
Immunoglobulin A
Vibrio
Antibodies
Freeze Drying
Inactivated
blood
Pharmaceutical
Chemistry
Author
Annika Borde
SuMo Biomaterials
Chalmers, Chemical and Biological Engineering, Pharmaceutical Technology
Anette Larsson
Chalmers, Chemical and Biological Engineering, Pharmaceutical Technology
SuMo Biomaterials
Jan Holmgren
University of Gothenburg
Erik Nygren
University of Gothenburg
European Journal of Pharmaceutics and Biopharmaceutics
0939-6411 (ISSN) 18733441 (eISSN)
Vol. 79 3 508-518Subject Categories
Pharmaceutical Sciences
Microbiology in the medical area
Chemical Sciences
Areas of Advance
Materials Science
DOI
10.1016/j.ejpb.2011.06.009
PubMed
21757004