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Infect Immun 2009 Apr;77(4):1475-82

Anthrax protective antigen delivered by Salmonella enterica serovar Typhi Ty21a protects mice from a lethal anthrax spore challenge.

Osorio M, Wu Y, Singh S, Merkel TJ, Bhattacharyya S, Blake MS, Kopecko DJ

Abstract

Bacillus anthracis, the etiological agent of anthrax disease, is a proven weapon of bioterrorism. Currently, the only licensed vaccine against anthrax in the US is AVA Biothrax(TM) which, although efficacious, suffers from several limitations. This vaccine requires six injectable doses over 18 months to stimulate protective immunity, requires the cold chain for storage, and in many cases has been associated with adverse effects. In this study, we have modified the B. anthracis protective antigen (PA) gene for optimal expression and stability, linked it to an inducible promoter for maximal expression in the host, and fused it to the secretion signal of the Escherichia coli alpha-hemolysin protein (HlyA) on a low copy plasmid. This plasmid was introduced into the licensed Typhoid vaccine strain, Salmonella enterica serovar Typhi strain Ty21a, and found to be genetically stable. Immunization of mice with three vaccine doses elicited a strong PA-specific serum IgG response with geometric mean titers of 30,000 (ranging from 5,800 to 157,000) and lethal toxin-neutralizing titers greater than 16,000. Vaccinated mice demonstrated 100% protection against a lethal intranasal challenge with aerosolized spores of B. anthracis 7702. The ultimate goal is a temperature stable, safe, oral human vaccine against anthrax infection that can be self-administered in a few doses over a short period of time.


Category: Journal Article
PubMed ID: #19179420 DOI: 10.1128/IAI.00828-08
PubMed Central ID: #PMC2663156
Includes FDA Authors from Scientific Area(s): Biologics
Entry Created: 2011-10-04 Entry Last Modified: 2012-08-29
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