The most effective vaccination targets for licensed anti-bacterial vaccines are surface polysaccharide capsules and lipopolysaccharide O side chains. However, a major limitation to more extensive development of these vaccines is the variability in carbohydrate structures and specificity of the immune response to immunizing antigens, necessitating the use of a large array of different vaccine antigens for comprehensive coverage. One potential solution is based on the development of vaccination and related studies targeting the highly conserved microbial surface polysaccharide, ß-1-6-linked poly-<i>N</i>-acetyl glucosamine (PNAG). This material coats the surface of over 75 different bacterial, fungal, apicomplexan and even filarial parasites. PNAG is naturally produced in a highly acetylated form (60-95% substitution of amino groups) and this glycoform primarily induces non-protective antibody. Deacetylation of the native polymer to &lt;35% acetylation or use of a synthetic oligosaccharide consisting of pentameric ß<b>-</b> 1-6-linked glucosamines conjugated to tetanus toxoid results in a structure that elicits functional, microbial-killing antibodies. In addition to numerous publications demonstrating the protective efficacy of active or passive immunity to PNAG against a range of infectious agents in animal challenge studies, we have also found that targeting PNAG can decrease pathology and/or lethality in a range of diseases not classically attributable to an infectious etiology. These include published results in murine models of inflammatory bowel disease and graft-versus host disease and recent studies in mouse models of type 1 diabetes (T1D) and Alzheimer’s disease (AD). Immunization of mice with the PNAG oligosaccharide conjugate vaccine prevented hyperglycemia in T1D-prone mice and cognitive and behavioral decline in AD-prone mice as well as accumulation of PNAG-positive microbial fragments in target tissues. In immunohistochemical studies, antibody to PNAG showed the presence of PNAG-positive microbial fragments in pancreata and brains of humans that died from T1D or AD, respectively, but not in humans that died from other causes. These data implicate the accumulation and continued presence of microbial fragments in tissues undergoing inflammatory destruction in the pathogenesis of many diseases and support the potential use of PNAG vaccines and monoclonal antibodies in ameliorating the consequences of microbial driven inflammation in many different diseases.

Do microbiota-derived microbial fragments embedded in inflamed tissues drive disease pathology? Evidence from the protective efficacy of a synthetic oligosaccharide-protein conjugate vaccine targeting the conserved microbial surface polysaccharide, PNAG against type 1 diabetes and Alzheimer’s disease

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.