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ANNUAL REPORT - Department of Biotechnology

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the pathogenesis <strong>of</strong> JE. It has been seen that JEV<br />

infection activates microglia both morphologically<br />

and functionally; infection leads to an elevation <strong>of</strong><br />

proinflammatory mediators for which microglia are<br />

predominantly responsible and the cytotoxins<br />

released from activated microglia are instrumental in<br />

inducing neuronal death that accompanies JE.<br />

Avian Influenza (H5N1) Virus<br />

A brain-storming session was organized by the<br />

<strong>Department</strong> on the status <strong>of</strong> Avian Influenza Research<br />

in India: Past, Present and Future on September 9,<br />

2006. Experts from India and USA participated and<br />

deliberated. The priority areas identified are genetic<br />

diversity, pathogenesis and zoonosis, diagnostics,<br />

vaccines. Accordingly, the <strong>Department</strong> has funded two<br />

R&D projects on development <strong>of</strong> a cost effective and<br />

easily up-scaleable multivalent vaccine using a novel<br />

yeast expressed virus like particles approach against<br />

the deadly Influenza A (H5N1) virus and molecular<br />

biology studies on the pathogenic strain <strong>of</strong> H5N1 virus<br />

(Indian isolate): protein-protein interaction based<br />

approach to study molecular evolution <strong>of</strong> the virus from<br />

its non-pathogenic strain at ICGEB, New Delhi.<br />

Malaria<br />

The project implemented at ICGEB, NIMR, New<br />

Delhi and Ispat General Hospital, Rourkela the cell<br />

bank and technology for production <strong>of</strong> recombinant<br />

PfMSP-119 and PfF2 were transferred to Bharat<br />

Biotech International Limited (BBIL), Hyderabad for<br />

developing master cell bank and master working cell<br />

bank for characterization. The BBIL has successfully<br />

produced cGMP grade material <strong>of</strong> three consistent<br />

batches at 10L scale for human clinical trial and<br />

toxicological studies. Efforts have been made to<br />

scale up to 50-100L ferment.<br />

Malaria vaccine trial site has been developed at<br />

Sundergarh District <strong>of</strong> Orissa to evaluate the malaria<br />

candidate vaccinogens PfMSP-119 and PfF2 through<br />

collection <strong>of</strong> clinical, entomological and molecular<br />

epidemiological /immunological indicators from the<br />

study. The group conducted longitudinal<br />

DBT Annual Report 2006-07<br />

106<br />

entomological surveys in two indicator villages each<br />

from forest and plan area. A total <strong>of</strong> 11 anopheline<br />

species from forest area and 10 speciies from plain<br />

area were recorded. It was observed that Anopheles<br />

Culificacies was the most predominants species and<br />

accounted for 41.2 and 36.5% <strong>of</strong> the total<br />

anophelines in forest and plain area respectively.<br />

Further observed that An. Fluviatilis was restricted to<br />

only forest area and its prevalence rate was 1.1%. It<br />

was measured that the antibody levels against<br />

PfMSP1 19,<br />

EBA 175 and TRAP antigens in 222 (110<br />

from forest and 112 from plain areas) and 248 (138<br />

from forest and 110 from plain areas) blood samples<br />

collected during low and high transmission seasons,<br />

respectively. The results suggest that there was a<br />

boosting in antibody production against these<br />

molecules by natural infectious in these individuals.<br />

The level <strong>of</strong> antibodies in study groups appeared to<br />

be related to their exposures to the parasite during<br />

high transmission phase. Update on progress on the<br />

project was reviewed in the month <strong>of</strong> January, 2007<br />

and decided to validate the data generated to initiate<br />

phase I/II clinical trial with malaria vaccinogens<br />

through national and international experts.<br />

A new multi-centric project entitled “Use <strong>of</strong><br />

artemisinin and curcumin combination in treatment <strong>of</strong><br />

uncomplicated P.falciparum malaria” was<br />

implemented at five institutions i.e. at National<br />

Institute <strong>of</strong> Malaria Research, Delhi; Indian Institute<br />

<strong>of</strong> Science, Bangalore; NIMR Field station,<br />

Rourkela; Ispat General Hospital, Rourkela and<br />

NIMR, Jabalpur.<br />

Another project implemented at IISc., Bangalore on<br />

development <strong>of</strong> candidate anti-malarials based on<br />

new drug targets, analyzed Pfcrt mutation as a<br />

marker for chloroquine resistance in 200 P.<br />

falciparum infected patients. Analysis <strong>of</strong> Pfmdr1 gene<br />

as a marker for chloroquine resistance has revealed<br />

that only around 30% <strong>of</strong> the Indian samples show the<br />

N86Y mutation, although in Africa there is a good<br />

correlation between K76T-Pfcrt mutation and N86Ymdr1<br />

mutation. The high prevalence <strong>of</strong> K76T- Pfcrt<br />

mutation in the Indian isolates <strong>of</strong> P.falciarum is a

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