Preparation and evaluation of a freeze-dried oral killed cholera vaccine formulation
Artikel i vetenskaplig tidskrift, 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.

immunology

Animals

field trial

immunology

Antibodies

immunology

risk

Freeze Drying

Freeze-drying

Mice

immunization

immunology

Microscopy

Calorimetry

Sucrose

Cholera Toxin

Vaccines

Pharmaceutical

Enzyme-Linked Immunosorbent Assay

Bacterial

toxin b-subunit

Differential Scanning

Inactivated

Pharmaceutical

Stabilization

Chemistry

Inbred BALB C

Scanning

biosynthesis

immunology

administration & dosage

Mannitol

vibrio-cholerae

antibodies

Oral

Trehalose

Electron

Small

chemistry

immunology

Mice

cholerae

Surface Properties

Cholera Vaccines

Vibrio

bangladesh

blood

Immunoglobulin A

Vibrio cholerae

chemistry

administration & dosage

Intestine

Administration

blood

X-Ray Diffraction

Lipopolysaccharides

escherichia-coli

biosynthesis

Technology

membranes

Författare

Annika Borde

SuMo Biomaterials

Chalmers, Kemi- och bioteknik, Farmaceutisk teknologi

Anette Larsson

SuMo Biomaterials

Chalmers, Kemi- och bioteknik, Farmaceutisk teknologi

Jan Holmgren

Göteborgs universitet

Erik Nygren

Göteborgs universitet

European Journal of Pharmaceutics and Biopharmaceutics

0939-6411 (ISSN)

Vol. 79 508-518

Ämneskategorier

Farmaceutisk vetenskap

Mikrobiologi inom det medicinska området

Kemi

Styrkeområden

Materialvetenskap

DOI

10.1016/j.ejpb.2011.06.009

PubMed

21757004