Novel innate polysaccharide agonists derived from Funtumia elastica tree bark (Yamoa™)

We have identified a unique polysaccharide innate adjuvant by screening using bovine γδ T cells. The screens were initiated to identify γδ T cell adjuvants, but the identified agonist was much more efficient at priming γδ T cell proliferation when accessory cells were present, suggesting a broader target cell range. The active polysaccharide fraction was isolated from Yamoa™ (ground bark of the Funtumia elastica tree) which is sold as a nutritional supplement. Microarray data from purified bovine γδ T cells and monocytes indicated that Yamoa™ stimulation resulted in a very similar gene expression pattern to that following stimulation with LPS, suggesting similar pathways. However, C3H:HeJ (TLR4 −/‐ ) mice were responsive to intraperitoneal injection of Yamoa™, indicating that despite their almost overlapping gene expression profiles, there is a TLR4 independent element in the Yamoa™‐derived polysaccharides. Specifically, the fraction that induces the most robust γδ T cell priming is TLR4 independent. Injection of Yamoa™ results in neutrophil recruitment and potentially enhances innate immunity in bovine and mouse models of Salmonella enterica serotype Typhimurium. Yamoa™ stimulation of human PBMCs resulted in large increases in GM‐CSF expression, and although changes in GM‐CSF were not detected in sera from Yamoa™ stimulated mice, increases in CXCL1/KC were, suggesting a possible mechanism for the observed neutrophil mobilization and innate protection. Thus, polysaccharide agonists derived from Yamoa™ are novel innate adjuvants with conserved activity and potential application in infectious disease settings.