DESIGN OF IMMUNOTOXINS; CONSTRUCTION OF VACCINES TO NEUTRALIZE ABRIN TOXICITY
The toxin Abrin, isolated from the Abrus precatorius plant, is a type II ribosome inactivating protein (RIP) that has a catalytic efficiency higher than any other toxin belonging to this class of proteins. Studies in the laboratory are focused on, delineating the signaling pathways triggered by abrin to kill cells by apoptosis, constructing immunotoxins for cell targeted immunotherapy and establishing a vaccine candidate for neutralizing abrin toxicity.
Unique monoclonal antibodies have been established to abrin that exhibit neutralization of the toxin activity in vitro and importantly, in vivo. The epitopes corresponding to the antibodies are being studied to enable design of small molecules/peptides as inhibitors of toxin activity
GLYCODELIN IN IMMUNOMODULATION
Glycodelin A, is a glycoprotein synthesized by the endometrium and decidua under progesterone regulation and has been implicated in suppression of the maternal immune system against the fetal allo-graft. Data from our laboratory have demonstrated that the immunomodulatory activity of glycodelin is mediated through apoptosis induced in activated T cells; the apoptotic activity is associated with cellular stress that gets translated to disturbance in the mitochondrial membrane potential leading to the activation of the caspase cascade. Studies to delineate the signaling cascade triggered by glycodelin, identified CD7 as its’ receptor that is expressed upon activation by antigens on T cells. The CD7 receptor-associated apoptotic events are being studied presently. The inhibitory effect of glycodelin was established also on other cells of the immune system, namely CTLS, B cells and monocytes. Currently the focus of the group is to determine the structure-function relationship of the glycans on glycodelin
IDENTIFICATION AND EVALUATION OF VIRUS NEUTRALIZING EPITOPES ON HEPATITIS C TYPE 3 VIRUS
Hepatitis C virus (HCV), is the major etiological agent of non-A, non-B hepatitis that infects almost 200 million people worldwide. Approximately 70-80% of HCV patients develop chronic hepatitis of which 20-30% leads to liver disease, cirrhosis and hepatocellular carcinoma. Treatment options for chronic HCV infection are limited, and a prophylactic vaccine is not available. An important consideration towards design of a vaccine for HCV infection would be identification of the B cell epitopes on the envelope protein of the virus that induce infection-neutralizing antibodies, thus can confer protective immunity. Mouse monoclonal antibodies against HCV-like particles have proved to be promising anti-virals. The epitope mapping of the neutralizing antibodies is being carried out to design peptides as candidate vaccines.
Copyright © 2014 - All Rights Reserved - Department of Biochemistry, IISc