ANNUAL REPORT - Department of Biotechnology

Chapter : 13
International Centre for Genetic Engineering and
Biotechnology (ICGEB)
ICGEB continued its efforts as per its mandates for
research in the field of biotechnology with special
reference to human health and agricultural related
plant biotechnology with focus on ICGEB member
states. During the course of the year ICGEB
organized three workshops on malaria, virology,
plant transformation and an international symposium
on tuberculosis research. The centre filed two
patents during the year and extended one to PCT.
Human Health
Malaria
The malaria group is working on development of
human malaria vaccine candidate antigens for
clinical trials; development of high through-put
screens to provide leads for antimalarials, and
characterisation of Plasmodium falciparum proteins
as novel drug targets; understanding the basic
biology of Red cell invasion and cytoadherence by
malaria parasite; and development of
conformationally constrained synthetic peptides as
peptido-memtics with diverse biological activities.
Red cell invasion and cytoadherence by malaria
parasites: The receptor-binding domains of these
proteins lie in conserved cysteine-rich regions that
are referred to as Duffy-binding-like (DBL) domains.
The crystal structure of the Plasmodium knowlesi
DBL domain has been solved by the Structural
Biology Group at ICGEB. The dual character of the
binding site mirrors the nature of the receptor given
that a sulfated tyrosine on DARC has been shown to
play a key role in the interaction. Antibodies raised
against the receptor binding domain of PvDBP
should thus be able to block binding and invasion by
diverse P. vivax field isolates, which bodes well for a
vaccine based on PvDBP.
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Sequestration of Plasmodium falciparum-infected
erythrocytes (IEs) in the placenta is implicated in
pathological outcomes of pregnancy-associated
malaria (PAM). Protective immunity to PAM is
associated with development of antibodies that
recognise diverse CSA-binding, placental P.
falciparum isolates.The epitopes recognised by such
protective antibodies are likely to lie in the DBL
domains of var genes encoding variant surface
antigens expressed on the surface of infected
erythrocytes. Immunisation of mice with the CSAbinding
DBL3γ domain of var1CSA elicits crossreactive
antibodies, which recognise and block
adhesion of diverse CSA-binding P. falciparum
laboratory strains and field isolates to placental cryosections
under flow. Antibodies raised against
DBL3γ of var1CSA cross-react with one of the CSAbinding
domains, DBL3X, of var2CSA, which is
upregulated in diverse CSA-binding isolates. Sera
from endemic areas recognise DBL3γ of var1CSA
and block its binding to CSA in a gender and paritydependent
manner indicating that it contains
epitopes recognised by protective antibodies. Thus,
it may be possible to target conserved epitopes in
CSA-binding DBL domains and develop novel
intervention strategies against PAM.
Malaria vaccine research: Laboratory protocols to
produce two major P. falciparum antigens to be used
as a malaria vaccines have been developed in
collaboration with an industrial partner. GMP grade
materials have been produced and toxicological
studies on the adjuvant formulated vaccines are
underway. The immunogenecity of the two
recombinant fragments of PfMSP-1 (PfMSP-142 and
PfMSP-119) have been compared. Passive
immunisation of mice with anti-PfMSP-142 IgG,
purified from immunised rabbit sera showed
International Centre for Genetic Engineering and Biotechnology