Zwitterionic polysaccharides (ZPSs), are unique in that they are known to activate CD4+ T-cells through the MHC II complex in the absence of peptide(s), lipids or proteins. Furthermore, they induce IgM to IgG class switching, invoke immune memory and essentially have challenged the paradigm of carbohydrate immune processing as T-cell independent antigens. Polysaccharide A1 (PS A1) is one of the most well-studied ZPSs and it is expressed on the surface of Gram-negative obligate anaerobic bacterium, Bacteroides fragilis ATCC 25285/NCTC 9343. Based on this unique property, we use the naturally occurring polysaccharide as a “carrier” in an entirely carbohydrate-based vaccine program for evaluating immunogenicity towards tumor associated carbohydrate antigens like Tn, TF and STn and carbohydrates affiliated with infectious disease. In order to further our understanding key immunological mechanisms, well-characterized synthetic constructs of designed oligomeric lengths are of high importance and substantial value for a variety of reasons. This talk will therefore focus on chemical methodology for the synthesis and evaluation of synthetic PS A1, conjugates thereof, immunobiology of designed constructs and our current venture into commercialized monoclonal antibodies.

Chemical methodology combined with immunogen development for novel immunotherapeutics

ACS Spring 2022

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