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This invention relates to improved methods of preparing Bacillus anthracis protective antigen (PA) for use in vaccines. PA is a secreted, non-toxic protein with a molecular weight of 83 KDa. PA is a major component of the currently licensed human vaccine (Anthrax Vaccine Adsorbed, AVA).

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.

Moraxella catarrhalis is one of the three leading causative agents of otitis media in children. This is due in part to the current immunizations of children with Streptococcus pneumoniae polysaccharide and conjugate vaccines to prevent otitis media. The proportion of otitis media caused by pneumococcal strains covered by the vaccines have decreased while those caused by Moraxella catarrhalis and nontypeable Haemophilus influenzae have significantly increased.

Ccr9^-/- mice may be useful for studying the role of CCR9 in T lymphocyte development and migration.

Mice will be distributed by The Jackson Laboratory; details about this mouse strain (Stock No. 027041) may be found at https://www.jax.org/strain/027041.

Anthrax, whether resulting from natural or bioterrorist-associated exposure, is a constant threat to human health. Bacillus anthracis is the causative agent of anthrax. It is surrounded by a polypeptide capsule of poly-gamma-D-glutamic acid (gamma-D-PGA), which is essential for virulence, is poorly immunogenic and has anti-phagocytic properties. Antibodies to the capsule have been shown to enhance phagocytosis and killing of encapsulated bacilli.

Niemann-Pick Disease, type C (NPC) is a rare, autosomal recessive, neurodegenerative disease. Approximately 95% of patients with NPC have mutations in NPC1, a gene implicated in intracellular cholesterol trafficking. Mutation of NPC1 causes intracellular accumulation of unesterified cholesterol in late endosomal/lysosomal structures and marked accumulation of glycosphingolipids, especially in neuronal tissue. Thus, NPC patients generally present with hepatosplenomegaly (enlargement of liver and spleen) and neurological degeneration.

This technology includes a series of diphenylpropanamides as potent and selective RORgt inhibitors for the treatment of Th17-related autoimmune diseases. The retinoic acid-related orphan receptor RORgt plays an important role in the differentiation of thymocytes, lymphoid tissue inducer cells, and inflammatory T helper-expressing interleukin 17a (Th17) cells. Small molecule RORgt inhibitors may provide means to regulate Th17 mediated immune response. The novel molecules have potential to treat Th17-related autoimmune diseases.

This technology includes the administration of the antiglucocorticoid mifepristone for the treatment of diabetes. Administration of mifepristone (50 mg orally every 6 hours) for one week improves hepatic and adipose insulin resistance in men and women with pre-diabetes or mild type 2 diabetes mellitus.