Monoclonal Antibodies That React With the Capsule of Bacillus anthracis
Posted Aug 30 2009 5:00pm
Description of Invention: Bacillus anthracis is the causative agent of anthrax and is surrounded by a polypeptide capsule of poly-gamma-D-glutamic acid (gammaDPGA). gammaDPGA is poorly immunogenic and has antiphagocytic properties. The bacterial capsule is essential for virulence. Antibodies to the capsule have been shown to enhance phagocytosis and killing of encapsulated bacilli. These antibodies in combination with antibodies that neutralize the toxins of B. anthracis could provide enhanced protection by their dual antibacterial and antitoxic activities. Such antibodies would be especially useful for antibiotic-resistant strains.
In order to obtain therapeutically useful anti-gamma DPGA monoclonal antibodies (MAbs), the inventors immunized chimpanzees with conjugates of 15-mer glutamic acid polymers to immunogenic protein carriers (recombinant protective antigen (PA) of B. anthracis). After several immunizations, chimpanzees developed strong immune responses to gammaDPGA. A combinatorial Fab library of mRNA derived from the chimpanzee's bone marrow was prepared and eight (8) distinct Fabs reactive with native gammaDPGA were recovered. Two (2) of the Fabs were converted into full-length IgG with human gamma1 heavy chain constant regions. These two (2) MAbs showed strong opsonophagocytic killing of bacilli in an in vitro assay. These two (2) MAbs were also tested for protection of mice challenged with virulent anthrax spores and results showed that both MAbs provided full or nearly full protection at a dose of 0.3 mg, the lowest dose tested, which is much more potent than previously reported murine anti-PGA MAbs. Since chimpanzee immunoglobulins are virtually identical to human immunoglobulins, these chimpanzee anticapsule MAbs may have clinically useful applications.
This application claims the antibody compositions described above. Also claimed are methods of treating or preventing B. anthracis infection in a mammalian host and isolated polynucleotides comprising a nucleotide sequence encoding the antibodies of the technology.
Applications: Development of anthrax vaccines, therapeutics and diagnostics.
Advantages: Strongly neutralizing antibodies, known regulatory pathway, potential for use as both a prophylaxis and therapy.
Development Status: Preclinical studies have been performed utilizing the monoclonal antibodies of this technology.
Inventors: Zhaochun Chen (NIAID) Robert H Purcell (NIAID) Rachel Schneerson (NICHD) Joanna Kubler-kielb (NICHD) Lily Zhongdong Dai (NICHD)
Collaborative Research Opportunity: The NIAID is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize MAbs neutralizing anthrax toxins and capsule for comprehensive protection against anthrax. Please contact Bill Ronnenberg, NIAID Office of Technology Development, at 301-451-3522 for more 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: firstname.lastname@example.org Phone: 301-435-4646 Fax: 301-402-0220