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Ninth Dr Yellapragada SubbaRow memorial Lecture of
Indra Prastha University, New Delhi
MISSION-ORIENTED RESEARCH ON RELEVANT PROBLEMS
An Immuno-Therapeutic Vaccine for
G P Talwar DSc
Founder-Director of the
National Institute of Immunology, Dr Talwar headed
the Department of Biochemistry at the All-India
Institute of Medical Sciences earlier for 27 years.
I shifted from basic studies on
the mechanism of action of hormones to a project
relevant to problems facing India when in 1970 a team
of distinguished immunologists accompanied by Dr
Howard Goodman of the World Health Organisation asked
me to head WHO Research and Training Centre in
Immunology for India and the South East Asia
Region. I was initially reluctant but agreed
when posed the question if I expected Americans to
solve the problem facing India as the country with the
largest number of lepers in the world.
It was a challenge. Lepers
evoked my sympathy but I knew nothing about
leprosy. I began to learn about leprosy,
spending the next two summers in the Danish Save the
Children Leprosaria in Orissa and Andhra Pradesh along
with two of my students and established a field
As discovered by Norwegians over 200 years back, leprosy
is caused by Mycobacterium leprae but there is no
medium in which a microbe can grow. M.
leprae obligatorily requires a host cell to grow.
Most (99%) of those who are exposed to it do not develop
leprosy. Those who do contract the disease fall in a
spectrum between polar tuberculoid TT and polar
lepromatous leprosy LL depending on the degree of immune
deficit. To understand the nature of immune deficit, it
was necessary to develop in vitro experimental systems.
My student, A D Krishnan, and I obtained macrophages from
monocytes of human blood which could be maintained in
culture. This could be employed as host cells to
determine the growth of M. leprae or lack of it
in various situations. The only source of M.
leprae was lepromas obtainable from LL patients.
These contained variable number of live and dead bacilli.
M. leprae is a slow grower with a division time
of 13 days.
To employ this inoculum to determine
growth demanded a novel approach. Counting was an
I thought of employing H3-thymidine as a discriminatory
tracer. It would be incorporated by M. leprae if
it would make DNA without interference from the host cell
which does not have the machinery to incorporate
H3-thymidine. By this approach, quantitative data
was obtained on the growth of M. leprae in a
Employing this system, we learnt that the T-cells of
patients played a critical role in generating a signal for
macrophages to either kill the resident M. leprae
or let it grow. We found that the nature of defect
in Lepromatous Leprosy was the inability of T-cells to
react with key antigens of M. leprae.
Our task next was to find a way to overcome this immune
deficit. We devised a heterogenous approach for searching
a Mycobacterium that could generate the signal from
T-cells of LL patients. We took all the known
mycobacteria including atypicals and investigated their
reaction to T cells. We found a non-pathogenic,
fast-growing mycobacterium that shared antigens with M.
leprae and M. tuberculosis. We code named it M.w.
After pre-clinical toxicology in the
1980s, we did Phase I study for human safety and Phase II
and Phase III studies for efficacy and then, with
approvals from DGCI and Ethics Committees, conducted
the field trials in 1990 at Kanpur, where leprosy is
endemic, and proved that Mw could be used as an
immunotherapeutic vaccine for multi-bacillary
Along with the standard multi-drug
regime, this shortened the recovery period and enhanced
The Mw vaccine was approved in 1994
by Drugs Controller General of India and then the US Food
and Drugs Agency.
We gave the technology to Cadila
Pharmaceuticals of Ahmedabad in return for `50,000 to the
National Institute of Immunology.
Treated with this vaccine, patients
recover to an extent that nobody believes that they had at
one time ugly lesions of LL. There is no relapse even
after a year whereas there is a 24.4% relapse with MDT
alone. Therefore the vaccine is being used along with MDT.
Mw vaccine has also been found to be
of utility in category 2 (‘difficult to
treat’) cases of tuberculosis. It completely
heals ugly ano-genital warts.
The gene sequence of Mw has been done by a consortium of
three national laboratories. Previously unlisted in
the World Data Bank, the marvellous bacillus has been
named after me as Mycobacterium indicus pranii.
(With inputs from Abhishek Gupta)
(Professor G P Talwar, Talwar Research Foundation, E-8 Neb
Valley, Neb Sarai, New Delhi 110068. P:
91-11-29531028/29536769. © 8800322055. email: email@example.com)