Immunization against anthrax using Bacillus subtilis spores expressing the anthrax protective antigen

Abstract Protective immunity to anthrax can be achieved by antibodies raised against the secreted protective antigen (PA) and this forms the basis of the current acellular vaccines for human use. Bacillus subtilis spores have previously been used for delivery of heterologous antigens by the oral and...

Full description

Saved in:
Bibliographic Details
Published in:Vaccine 2007-01, Vol.25 (2), p.346-355
Main Authors: Duc, Le H, Hong, Huynh A, Atkins, Helen S, Flick-Smith, Helen C, Durrani, Zarmina, Rijpkema, Sjoerd, Titball, Richard W, Cutting, Simon M
Format: Article
Language:English
Subjects:
Allergy and Immunology
Animals
Anthrax
Anthrax - prevention & control
Anthrax vaccine
Anthrax Vaccines - immunology
Antibodies, Bacterial - blood
Antigens, Bacterial - immunology
Applied microbiology
Bacillus subtilis
Bacterial Toxins - immunology
Biological and medical sciences
Endospores
Female
Fundamental and applied biological sciences. Psychology
Heat-stable vaccine
Immunization
Immunoglobulin G - blood
Immunoglobulin G - classification
Mice
Mice, Inbred BALB C
Microbiology
Neutralization Tests
Spores, Bacterial
Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects)
Vaccines, Synthetic - immunology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract Protective immunity to anthrax can be achieved by antibodies raised against the secreted protective antigen (PA) and this forms the basis of the current acellular vaccines for human use. Bacillus subtilis spores have previously been used for delivery of heterologous antigens by the oral and nasal routes and their intrinsic heat-stability make them attractive vaccine vehicles. In this study we have expressed PA, or segments of PA, in B. subtilis using two strategies. First, display on the spore coat, and second, in the germinated spore (or vegetative cell). Using parenteral delivery we show that recombinant spores can be used to confer protective immunity in a murine model using an in vitro toxin neutralization assay and a challenge experiment with the latter showing protection to 100 median lethal dose of B. anthracis spores. PA must be secreted from the live bacterium or alternatively displayed on the spore surface to confer protective immunity. Intracellular expression of PA failed to confer protective immunity. The highest levels of protective immunity were achieved when PA was displayed on the spore surface as well as in the germinating spore.
ISSN:0264-410X
1873-2518
DOI:10.1016/j.vaccine.2006.07.037