Mycobacterium w (M.w),
is a cultivable, nonpathogenic and rapidly growing Mycobacterium
classifiable in Runyon Group IV along with other rapid growers
such as M. fortuitum, M. smegmatis, M.
chelonae and M. vaccae on the basis of its growth
and metabolic properties (Reddi et al., Int. J. Lepr. Other
Mycobact. Dis. 1994, 62:229-36). This species of the genus Mycobacterium,
interestingly, shares a number of common B and T cell determinants
with Mycobacterium leprae and Mycobacterium tuberculosis
(Zaheer et al., J. Infect. Dis. 1993, 167:401-10).
Due to this fact, Mycobacterium
w was used as the first, candidate leprosy vaccine strain.
Immunotherapy with killed Mycobacterium w (M. w)
vaccine was attempted in patients with borderline-lepromatous
(BL), or lepromatous leprosy (LL) to determine whether immunization
can hasten recovery and reduce the treatment time by invigorating
cell-mediated immunity. Patients receiving the vaccine had rapid
clinical improvement and was found to significantly reduce the
bacterial burden (Zaheer et al., J. Infect. Dis. 1993, 167:401-10).
A significant number of vaccinated patients demonstrated an
upgrading in the histopathology of skin lesions. Rapid bacterial
clearance was accompanied by distinct signs of clinical improvement
in all such patients (Talwar et al., Vaccine. 1990, 8(2):121-9).
This vaccine administered in various
forms was initially developed at the National Institute of Immunology,
New Delhi (India) and extensive clinical trials have been completed
towards validation for field level testing. Copious data on
immunotherapeutic significance of M. w emerged during
clinical trials involving 80,000 subjects in India (India to
sell leprosy vaccine. Asia Pacific Biotech News. 1998, 1 (30)
pp 614). Following this, the Indian Government has already approved
commercial level production of this theraputic vaccine and the
technology was subsequently transferred to Cadila Pharmaceuticals
in Ahmedabad, India.
In view of the post genomic revelations
on the mechanisms of mycobacterial pathogenesis and infection
biology of tuberculosis, there is a need to revisit the biology
of immunological cross reactivities between the M. leprae
and M.w in a more effective manner. It is important
to identify and characterize antigens of M.w that trigger
T-cell responses in leprosy patients vaccinated with this organism
and the mechanisms thereof (Yadava et al., Scand. J. Immunol.
1991 34:23-31) . For such studies, detailed knowledge of genome
content, gene regulation, metabolic cascades, evolutionary genetics,
antigenicity and survival mechanisms is required. These aspects
of M.w are till now unexplored and it remains a largely
unstudied bacillus at the genomic and proteomic levels, given
few efforts on its molecular characterization by genotypic analyses
of selected gene loci (Reddi et al., Int. J. Lepr. Other Mycobact.
Dis. 1994, 62:229-36).
Thus, there is a need
for deciphering the biology of this bacillus by complete sequencing
and analysis of its genome. Subsequent studies on comparative
genomics (with M. tuberculosis, M. bovis,
M. bovis BCG, M. leprae and M. avium)
and biology components of the study will enhance our knowledge
about possible mechanisms involved in its clearance in leprosy
patients and efficacy as a vaccine candidate for leprosy and
other mycobacterial diseases. This will also help in generating
useful data on evolution of mycobacterial genome and the mysterious
phenomenon of genomic downsizing (as seen in M. leprae
and M. tuberculosis, M. bovis, and possibly
in M. w. as well).
In view of this, DBT
has supported a project on "The
Mycobacterium w Genome Program: Complete Genome Sequencing