Methods for Preparing Bacillus anthracis Protective Antigen for Use in Vaccines
Posted Aug 31 2008 5:00pm
Description of Invention: 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.
Applications: Improved B. anthracis vaccines.
Advantages: 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 Status: Phase I clinical studies are being performed.
Inventors: Joseph Shiloach (NIDDK) Stephen H Leppla (NIDCR) Delia Ramirez (NIDDK) Rachel Schneerson (NICHD) John B Robbins (NICHD)
DM Ramirez et al. Production, recovery and immunogenicity of the protective antigen from a recombinant strain of Bacillus anthracis. J Ind Microbiol Biotechnol. 2002 Apr;28(4):232-238. [ PubMed abs ]
Licensing Status: Available for exclusive or nonexclusive licensing.
Collaborative Research 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 Rochelle S. Blaustein, J.D., at 301/451-3636 or Rochelle.Blaustein@nih.gov for additional information.
For Additional Information Please Contact: Peter Soukas J.D. NIH Office of Technology Transfer 6011 Executive Blvd. Suite 325
Room 14, Rockville, MD 20852-3804 United States Email: soukasp@mail.nih.gov Phone: 301-435-4646 Fax: 301-402-0220
Description of Invention:
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.
Applications:
Improved B. anthracis vaccines.
Advantages:
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 Status:
Phase I clinical studies are being performed.
Inventors:
Joseph Shiloach (NIDDK)
Stephen H Leppla (NIDCR)
Delia Ramirez (NIDDK)
Rachel Schneerson (NICHD)
John B Robbins (NICHD)
Patent Status:
HHS, Reference No. E-023-2002/0
US, Application No. 10/290,712 filed 08 Nov 2002
US, Application No. 12/816,285 filed 15 Jun 2010
Relevant Publication:
Licensing Status:
Available for exclusive or nonexclusive licensing.
Collaborative Research 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 Rochelle S. Blaustein, J.D., at 301/451-3636 or Rochelle.Blaustein@nih.gov for additional information.
Portfolios:
Infectious Diseases
Infectious Diseases - Vaccines
Infectious Diseases - Other
Rare Diseases
For Additional Information Please Contact:
Peter Soukas J.D.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325 Room 14,
Rockville, MD 20852-3804
United States
Email: soukasp@mail.nih.gov
Phone: 301-435-4646
Fax: 301-402-0220
Ref No: 550
Updated: 09/2008