Methods for Preparing Bacillus anthracis Protective Antigen for Use in Vaccines


This invention relates to improved methods of preparing Bacillus anthracis protective 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 of Bacillus anthracis are 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 of B. anthracis (BH445). One of the PA variants described in the patent application lacks the furin and chymotrypsin cleavage sites.

Potential Commercial Applications: Competitive Advantages:
  • Improved B. anthracis vaccines.
 
  • Bacillus anthracis protective 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 by B. anthracis. The vaccines claimed in this application are intended for active immunization for prevention of B. anthracis infection, and for preparation of immune antibodies.


Development Stage:
Phase I clinical studies are being performed.

Inventors:

Joseph Shiloach (NIDDK)  ➽ more inventions...

Stephen Leppla (NIDCR)  ➽ more inventions...

Delia Ramirez (NIDDK)  ➽ more inventions...

Rachel Schneerson (NICHD)  ➽ more inventions...

John Robbins (NICHD)  ➽ more inventions...


Intellectual Property:
U.S. Pat: 7,763,451 issued 2010-07-27
U.S. Pat: 8,703,150 issued 2014-04-22
U.S. Pat: 8,044,189 issued 2011-10-25
US Application No. 12/816,285

Publications:
Ramirez DM, et al. PMID 11986925

Collaboration Opportunity:

The National Institutes of Health is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize methods of preparing Bacillus anthracis protective antigen (PA) from a cell or organism, particularly a recombinant cell or microorganism, for use in vaccines. Please contact Martha Lubet, Ph.D. at 240-276-5508 or lubetm@mail.nih.gov for additional information.


Licensing Contact:
Martha Lubet, Ph.D.
Email: lubetm@mail.nih.gov
Phone: 240-276-5508

OTT Reference No: E-023-2002-0
Updated: May 4, 2018