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Dissecting the Cellular Immune Response in Visceral Leishmaniasis

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Title Dissecting the Cellular Immune Response in Visceral Leishmaniasis
 
Creator Guha, Rajan
 
Subject Infectious Diseases and Immunology
 
Description Protozoan parasites in the genus Leishmania are responsible for a spectrum of human diseases termed Leishmaniasis. It is one of the major tropical diseases that has affected both
the New World as well as the Old World countries, whose manifestations in humans range from mild cutaneous lesions to fatal visceral infections if left untreated. Failure of the pentavalent antimonials, the present main form of chemotherapeutic treatment worldwide, is attributed to the emergence of antimonial-resistant Leishmania strains resulting in frequent relapses after treatment.In India, antimony is no longer useful as a drug because 65% of VL
patients fail to respond or promptly relapse. Alternative chemotherapeutic treatments with amphotericin B and its lipid formulation have severe limitations due to their toxic effect and prohibitive high cost of treatment. Growing limitations in available chemotherapeutic
strategies due to emerging resistant strains and lack of an effective vaccine strategy against VL deepens the crisis. Despite years of antileishmanial vaccine research and improved strategies, no vaccine has yet protected against Leishmania donovani challenge. We would
like to focus our study on the aspect of immune regulation by SAG sensitive (Sb-S) and SAG resistant (Sb-R) parasite. During infection the parasites evokes severe immune suppression in the host. We would like to study whether a Sb-S and Sb-R parasite initiates different types of
response in the host during early and late hours of infection.The second part of my study will focus on the development of vaccine against visceral leishmaniasis. Protein based vaccination with gp63 and LACK antigens have shown promise, but lack of suitable Th1 driving adjuvant
has limited their use beyond the laboratory. Vaccination with attenuated parasites has shown considerable protection against virulent challenges together with the ability to drive Th1 response. But absence of clear genetic markers for attenuated parasites and the risk of attenuation reversal, their use as field vaccine are deplorable. Our lab has developed an effective DNA vaccine, a kinetoplastid membrane protein-11 (KMP-11)-encoding construct
protected extremely susceptible golden hamsters from both pentavalent antimony responsive (AG83) and antimony resistant (GE1F8R) virulent L. donovani challenge. KMP-11 is known as a host protective molecule in visceral leishmaniasis, as the protein contains both B cell &
T cell epitopes. My objective is to develop a new route of administration leading to effective human trial. . Recent reports suggest promising result using viral vectors, we will try to use viral vectors as a delivery vehicle.We will try to include different potential DNA vaccin
 
Date 2012
 
Type Thesis
NonPeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/1873/1/RAJAN_THESIS.pdf
Guha, Rajan (2012) Dissecting the Cellular Immune Response in Visceral Leishmaniasis. PhD thesis, Jadavpur University.
 
Relation http://www.eprints.iicb.res.in/1873/