DNA Promoters and Anthrax Vaccines
Currently, the only licensed vaccine against anthrax in the United States is AVA BioThrax®, which, although efficacious, suffers from several limitations. This vaccine requires six injectable doses over 18 months to stimulate protective immunity, requires a cold chain for storage, and in many cases has been associated with adverse effects.
This application claims a modified 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 to the secretion signal of the Escherichia coli alpha-hemolysin protein (HlyA) on a low-copy-number plasmid. This plasmid was introduced into the licensed typhoid vaccine strain, Salmonella enterica serovar Typhi strain Ty21a, and was found to be genetically stable. Immunization of mice with three vaccine doses elicited a strong PA-specific serum immunoglobulin G response with a geometric mean titer of 30,000 (range, 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.
Potential Commercial Applications:
- Anthrax vaccines, therapeutics and diagnostics.
- Vector is well-characterized.
- Simple manufacturing process.
- Potential low-cost vaccine.
- Oral vaccine - avoids needles and can be administered rapidly during emergencies.
- Temperature-stable manufacturing allows for vaccine distribution without refrigeration.
U.S. Pat: 7,758,855 issued 2010-07-20
U.S. Pat: 8,247,225 issued 2012-08-21
U.S. Pat: 8,709,813 issued 2014-04-29
US Application No. 14/185,353
PCT Application No. PCT/US2004/030616
Various international patents issued
Osorio M, et al. PMID 19179420
Bill Ronnenberg, JD-MIP, MS
FDA Technology Transfer Program
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OTT Reference No: E-344-2003/1
Updated: August 4, 2015