Feng Lab Projects

Clostridium difficile Vaccine Development

The goal of this project is to design a vaccine that targets both TcdA and TcdB, with a view to elicit strong systemic and mucosal immunity to prevent CDI, reduce the severity, or eliminate an ongoing chronic disease. We propose to exploit the recently expressed atoxic C. difficile holotoxin proteins in an endotoxin-free Bacillus megaterium system. Two immunogens will be evaluated: a mixture of atoxic full-length C. difficile toxin A and B generated by point mutations (designated as aTxAB), and a chimera protein containing full-length TcdB but with its receptor binding domain replaced with that of TcdA (designated as cTxAB). cTxAB has a small deletion (97 amino acids) in transmembrane domain rendering it non-toxic. Preliminary studies showed that atoxic TcdB vaccination induced antibody responses against a wide-spectrum of epitopes and potent protective immunity superior to toxoid; cTxAB immunization induced antibody and protective responses against both TcdA and TcdB.

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Epithelium, Dendritic Cells, and Clostridum difficile Associated Colitis

Our long-term goal is to understand the mechanisms mediating intestinal inflammation in C. difficile infection and to utilize this knowledge for the design of better immune interventions in order to reduce the incidence of CDI and severity of the disease. The interaction of intestinal epithelial cells (IECs) with intestinal antigen presenting cells (APCs), such as dendritic cells (DCs) and macrophages, in the gut orchestrates mucosal immune homeostasis and inflammatory response. Our objective is to elucidate the immune response of IECs and intestinal DCs after their exposure to C. difficile toxins and to determine the nature of their interaction on initiating intestinal inflammation and tissue destruction.

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