Discovery of Parasite-Derived Tolerogenic Adjuvants

Our goal is to identify novel parasite derived immunomodulatory tolerogenic adjuvants that can suppress pro inflammatory and autoimmune disease statessuch as typediabeteswhich has no disease modifying treatmentParasitic helminths establish chronic infection by modulating host innate and adaptive immune responsesdown regulating T effector cellsstimulating Thand or inducing regulatory B and T cellsSeveral helminth excretory secretoryE Sproteins are known to modulate the immune responseswhich raises the exciting possibility that they can be exploited as biologicsIn this contractBrugia malayi will be screened for tolerogenic proteinsAimwill perform comparative analyses using well defined bioinformatic tools to identifyfilariae E S stage specific proteinsthese potential tolerogenic proteins will be expressed and subjected in Aimto systematic in vitro screening using human cells from healthy donorsThe topproteins with clear tolerogenic characteristics will be assessed in Aimfor their potential cytotoxicityAimwill testtop candidates with cells from T D patients to identify proteins that modulate monocyte lineage cells to ultimately suppress autoreactive effector T cellsThis innovative screening scheme driven by bioinformatics power and immunological readouts will discover disease modifying tolerogenic adjuvant candidates that could lead to a novel therapeutic paradigm