The overall goal in Dr. Feng's Lab is to develop novel immune-based preventive strategies against major MDR pathogens in developing and developed countries. Successful preclinical validation of the lead candidates will also allow further development and large- scale efforts for eventual commercialization of these products against C. difficile and C. jejuni diseases, for which we currently have no effective preventative measures.
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.
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.
Vice Chair of Department of Microbial Pathogenesis and Professor, Principal Investigator
Hanping Feng, PhD, began his training at the University of Arizona where he received his PhD in 2002 with his thesis titled 'Immunological Consequence of Apoptosis in a Tumor System'. He then received postdoctoral training in Center for Blood Research
Vice Chair of Department of Microbial Pathogenesis and Professor, Principal Investigator
Hanping Feng, PhD, began his training at the University of Arizona where he received his PhD in 2002 with his thesis titled 'Immunological Consequence of Apoptosis in a Tumor System'. He then received postdoctoral training in Center for Blood Research at Harvard Medical School. Feng became an assistant research professor in 2004 in the Department of Biomedical Science at Cummings Veterinary Medicine School of Tufts University. Feng moved up to the rank of associate research professor and then associate professor at Tufts University till he accepted a position at the University of Maryland, Baltimore at the end of 2011.
Postdoctoral Fellow
Office 7403
Telephone: 410-706-3611
Establishment of a gnotobiotic pig model of Clostridioides difficile infection and disease. Nyblade C, Parreno V, Zhou P, Hensley C, Oakes V, Mahsoub HM, Kiley K, Frazier M, Frazier A, Zhang Y, Feng H, Yuan L. Gut Pathog. 2022 Jun 6;14(1):22. doi: 10.1186/s13099-022-00496-y. PMID: 35668452.
The development of live biotherapeutics against Clostridioides difficile infection towards reconstituting gut microbiota. Zhang Y, Saint Fleur A, Feng H. Gut Microbes. 2022 Jan-Dec;14(1):2052698. doi: 10.1080/19490976.2022.2052698. PMID: 35319337.
Spray layering of human immunoglobulin G: Optimization of formulation and process parameters. Jiang B, Yu D, Zhang Y, Yu H, Feng H, Hoag SW. Int J Pharm. 2021 Dec 15;610:121238. doi: 10.1016/j.ijpharm.2021.121238. Epub 2021 Nov 5. PMID: 34748814
A probiotic yeast-based immunotherapy against Clostridioides difficile infection. Chen K, Zhu Y, Zhang Y, Hamza T, Yu H, Saint Fleur A, Galen J, Yang Z, Feng H. Sci Transl Med. 2020 Oct 28;12(567):eaax4905. doi: 10.1126/scitranslmed.aax4905. PMID: 33115949.
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