Members
Leah Ben Tradyon (Leslie A. Mitchell), Ph.D.,Head Scientist;
Evelyne Zeira, Research Scientist;
Carol Levi, Animal Farm Technician
Scientific activities
Currently, this group is investigating the immune response (both antibody- and T-lymphocyte-mediated) to hepatitis viruses, including hepatitis A virus (HAV) and hepatitis C virus (HCV).
HAV studies focus on new formulations for HAV vaccines (edible, plant-produced transgenic HAV antigens) and strategies for delivery of these antigens via the mucosal (oral or intrarectal) routes.
One group of HCV studies focuses on identification of antigenic sites (epitopes) on HCV proteins that are dominant in the human T-lymphocyte response to HCV, in the immunogenetic control (definition of HLA Class II restriction elements) of these immune responses, and in the relevance of these immune responses to HCV disease outcome (i.e., their association with spontaneous clearance of virus and recovery or development of chronic infection). Identification of epitopes associated with a protective immune response to HCV (viral clearance) will facilitate the design of HCV vaccines.
A second group of HCV studies involves the generation of transgenic plasmo / adenoretroviruses containing inserts of HCV DNA sequences for antigenic epitopes relevant to immune protection, or of therapeutic value in controlling HCV-induced inflammation in the liver. These retroviral constructs will be tested in small animal models for their ability to induce appropriate immune responses.
Collaborations
Eithan Galun, MD, Director, Gene Therapy Institute, Hadassah Ein Kerem: The group collaborates with Prof. Galun who is a co-investigator in all project areas listed above. Prof. Galun has developed a small animal model for evaluation of immunologic and other therapeutic intervention for control of hepatitis virus B and C infections. The group will use this model in preliminary evaluation of the immunogenicity and potential efficacy of candidate HCV vaccine antigens. Prof. Galun will also provide clinical data and samples from the Hadassah Ein Kerem Liver Diseases Clinic for the study of the human T-lymphocyte response to HCV antigens.
Chaim Brautbar, PhD and Shoshana Israeli, PhD, HLA Typing Laboratory, Hadassah Ein Kerem: Drs. Brautbar and Israeli who head the HLA Typing Laboratory, collaborate with this working group on projects involving determination of human immunogenetic background (HLA Class II phenotypes and genotypes) in relation to response to diseases caused by hepatitis viruses.
Yaacov Baruch, MD, Rambam Medical Center: Dr. Baruch is the Director of the Liver Diseases Clinic at Rambam Medical Center in Haifa. He has >12 years experience in liver disease, liver transplantation, pathophysiology of liver diseases, including those caused by hepatitis viruses. Dr. Baruch is providing documented patient samples from the Liver Diseases Clinic for studies involving the human T-lymphocyte response to HCV.
Gerald T. Nepom, MD, PhD, Virginia Mason Research Center: Dr. Nepom who is the Director of the Virginia Mason Research Center/Benaroya Research Institute located in Seattle, Washington, USA, has been a collaborator with Dr. Mitchell for the past 10 years on projects involving immunogenetic (HLA Class II) control of resistance and susceptibility to human diseases. He has > 15 years experience in immunogenetics of susceptibility and resistance to autoimmune diseases (in particular, Type 1 diabetes and rheumatoid arthritis).
Dr. Nepom who is internationally renowned for his work in human immunogenetics, has been at the forefront of innovative research and the development of molecular biologic techniques for identifying HLA Class II restriction elements associated with disease susceptibility and the mapping of T cell epitopes of relevance to human disease, and has over 200 publications in this area. His role as a co-investigator in studies involving the human T-lymphocyte response to HCV epitopes will be to provide input into interim data analysis that will assist in establishing HLA Class II allelic relationships with outcome of HCV infection in the patient study subjects.
This information will be used by Dr. Nepom and his colleagues to predict (using computer algorithms) HCV peptide sequences which should be investigated further with respect to Class II allelic associations with HCV disease, and for the construction of HLA tetramers which will be used to determine if there are specific peptide-reactive T cells present in peripheral blood lymphocytes of Israeli HCV patients who are subjects of our studies.