Bacillus anthracis is a spore-forming bacterium that causes anthrax in humans and in other mammals. The glycoprotein BclA (Bacillus collagen-like protein of anthracis) is a major constituent of the exosporium, the outermost surface of B. anthracis spores. The glycosyl part of BclA is an oligosaccharide composed of 2-O-methyl-4-(3-hydroxy-3-methylbutanamido)-4,6-dideoxy-d-glucose, referred to as anthrose, and three rhamnose residues. A structure similar to anthrose, 4-(3-hydroxy-3-methylbutanamido)-4,6-dideoxy-d-glucose is found in the side chain of the capsular polysaccharide (CPS) of Shewanella spp. MR-4. Under certain growth conditions the bacteria produce a variant CPS lacking one methyl group on the hydroxybutyrate, 4-(3-hydroxybutanamido)-4,6-dideoxy-d-glucose. Contrary to anthrose, neither of the Shewanella CPSs is 2-O methylated.

The inventors have found that both Shewanella CPS variants react with anti-B. anthracis spore sera. The inventors have also found that these antisera reacted with flagellae of Pseudomonas syringae, reported to be glycosylated with a similar terminal saccharide, 4-(3-hydroxybutanamido)-4,6-dideoxy-2-O-methyl-d-glucose. Sera produced by immunization with Shewanella or P. syringae cells bound to B. anthracis spores but not to Bacillus cereus spores in a fluorescent microscopy assay. The inventors’ experiments show that methylation of the anthrose at the O-2 of the sugar ring and at the C-3 of 3-hydroxybutyrate are not essential for induction of cross-reactive antibodies.

The application claims the use of Shewanella CPS conjugates as a component of an anthrax vaccine.  The application also claims the use of capsular polysaccharides from Shewanella and compounds from the flagella of Pseudomonas syringae for the development of anthrax vaccines.

Application:

Development of anthrax vaccines, diagnostics and therapeutics.

Development Status:

Conjugates have been synthesized and preclinical studies have been performed.

Publication:

J Kubler-Kielb et al. Saccharides cross-reactive with Bacillus anthracis spore glycoprotein as an anthrax vaccine component. Proc Natl Acad Sci USA. 2008 Jun 24;105(25):8709-8712 [PubMed abs].  This publication reports the preparation, characterization, and antibody responses to protein conjugates of the two variants of Shewanella CPS.  Significantly, both conjugates induced antibodies that bound to both Shewanella CPS variants by ELISA and to B. anthracis spores, as detected by fluorescent microscopy.

U.S. Provisional Application No. 61/066,509 filed 19 Feb 2008 (HHS Reference No. E-032-2008/0-US-01)

Inventors:

Joanna Kubler-Kielb (NICHD), Rachel Schneerson (NICHD), Haijing Hu (NIAID), Stephen H. Leppla (NIAID), John B. Robbins (NICHD), et al.

Licensees Sought:

Available for exclusive or non-exclusive licensing.