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 3 508-518

Subject 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

More information

Created

10/7/2017