Preparation and evaluation of a freeze-dried oral killed cholera vaccine formulation

• 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.

Ämnesord

NATURVETENSKAP  -- Kemi (hsv//swe)

NATURAL SCIENCES  -- Chemical Sciences (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Microbiology in the medical area (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)

Nyckelord

Freeze-drying

Stabilization

Mannitol

Sucrose

Trehalose

Vibrio

cholerae

toxin b-subunit

vibrio-cholerae

field trial

escherichia-coli

immunization

antibodies

bangladesh

membranes

risk

Administration

Oral

Animals

Antibodies

Bacterial

biosynthesis

blood

Calorimetry

Differential Scanning

Chemistry

Pharmaceutical

Cholera Toxin

immunology

Cholera Vaccines

administration & dosage

chemistry

immunology

Enzyme-Linked Immunosorbent Assay

Freeze Drying

Immunoglobulin A

biosynthesis

blood

Intestine

Small

immunology

Lipopolysaccharides

immunology

Mice

Mice

Inbred BALB C

Microscopy

Electron

Scanning

Surface Properties

Technology

Pharmaceutical

Vaccines

Inactivated

administration & dosage

chemistry

immunology

Vibrio cholerae

immunology

X-Ray Diffraction

immunology

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