Available Technology

Methods for PreparingBacillus anthracisProtective Antigen for Use in Vaccines

This invention relates to improved methods of preparingBacillus anthracisprotective antigen (PA) from a cell or organism, particularly a recombinant cell or microorganism, for use in vaccines. Production and purification methods of modified PA from a non-sporogenic strain ofBacillus anthracisare described. Specifically, a scalable fermentation and purification process is claimed that is suitable for vaccine development, and that produces almost three times more product than earlier-reported processes. This is accomplished using a biologically inactive protease-resistant PA variant in a protease-deficient non-sporogenic avirulent strain ofB. anthracis(BH445). One of the PA variants described in the patent application lacks the furin and chymotrypsin cleavage sites.
Benefits 
Bacillus anthracisprotective antigen is a major component of the currently licensed human vaccine (Anthrax Vaccine Adsorbed, AVA). Although the current human vaccine has been shown to be effective against cutaneous anthrax infection in animals and humans and against inhalation anthrax in rhesus monkeys, the licensed vaccine has several limitations: (1) AVA elicits a relatively high degree of local and systemic adverse reactions, probably mediated by variable amounts of undefined bacterial products, making standardization difficult; (2) the immunization schedule requires administration of six doses within an eighteen (18) month period, followed by annual boosters; (3) there is no defined vaccine-induced protective level of antibody to PA by which to evaluate new lots of vaccines; and (4) AVA is comprised of a wild-type PA. Thus a vaccine comprising a modified purified recombinant PA would be effective, safe, allow precise standardization, and require fewer injections. The invention also relates to PA variants, and/or compositions thereof, which are useful for eliciting an immunogenic response in mammals, particularly humans, including responses that provide protection against, or reduce the severity of, infections caused byB. anthracis. The vaccines claimed in this application are intended for active immunization for prevention ofB. anthracisinfection, and for preparation of immune antibodies.
applications 
Inventors: 
Joseph Shiloach
Internal Laboratory Ref #: 
E-023-2002/0
Lab Representatives
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