Zwitterionic polysaccharides

Bacterioides fragilis is a gram-negative anaerobe and a prototypic gut commensal organism. B. fragilis is able to produce eight different capsular polysaccharides, which envelope the organism and form its protective capsule. Polysaccharide A (PSA) is one of these polysaccharides and, interestingly, has a unique zwitterionic motif that includes alternating positively and negatively charged sugar residues. PSA consists of a tetrasaccharide repeat unit that forms a polymer of between 30-300 repeats.

Such bacterial capsular polysaccharides are well known to industry, and are the basis of polysaccharide conjugate vaccines used successfully for decades in millions of people. This specific zwitterionic polysaccharide (ZPS) was shown, in a series of landmark papers by our company’s scientific founders that overturned established immunologic paradigms, to be processed via the endosomal pathway in antigen-presenting cells, depolymerized by NO-dependent deamination, and presented to CD4+ T-cells by MHC class II molecules.

Thus, conventional wisdom that only protein antigens are presented by MHC class II was overturned. Upon presentation, such ZPS molecules are able to induce the activation and proliferation of CD4+ T cells, and control the Th1/Th2 physiologic balance. Our recent published work has demonstrated the capacity of ZPS therapeutics to protect against experimental models of inflammatory bowel disease (IBD) and multiple sclerosis (MS). Based on the discovery of fundamentally new biology that has been described in over 100 scientific publications, we are advancing development on a new class of ZPS therapeutics.