Association of HLA antigens with differential responsiveness to Mycobacterium w vaccine in multibacillary leprosy patients.

Leprosy patients undergoing phase II trials in two hospitals of New Delhi, India, were HLA typed to see the association of HLA with differential responsiveness to Mycobacterium w vaccine. The vaccine comprises an atypical, nonpathogenic mycobacterium, Mycobacterium w, which has cross-reactive antigens with M. leprae. Multibacillary patients who are lepromin negative are vaccinated at an interval of 3 months. Considerable improvement is evident in the patients in terms of a decline in bacterial indices and histopathological and immunological upgrading. But all the patients do not respond to the vaccine in the same manner; some are slow responders, while others are good responders. HLA-A28 and DQw3 (DQw8 + 9) were found to be associated with slow responsiveness, while DQw1 and DQw7 were found to be associated with a more rapid responsiveness to the M. w vaccine. However, these associations were not significant after P correction for the number of antigens tested for each locus except for HLA-DQw3 (DQw8 and DQw9) and DQw7. DQw7, a new defined split of HLA-DQw3, seems to be associated with the responsiveness to M. w vaccine.

Immunological upgrading with combined immunotherapy and chemotherapy in a lepromatous leprosy patient: a case report.

Immunotherapy with Mycobacterium w was given, in addition to standard multidrug therapy (MDT) to a lepromatous leprosy (LL) patient with a bacteriological index (BI) of 6. After 15 months of treatment this patient attained bacteriological negativity and clinical inactivity. Histopathologically the patient upgraded to borderline-tuberculoid at 12 months, and at 15 months showed features of nonspecific infiltration in the dermis. The rapid immunological upgrading seen in the patient is highlighted in this paper.

T-cell responses to fractionated antigens of Mycobacterium w, a candidate anti-leprosy vaccine, in leprosy patients.

Mycobacterium w, an atypical cultivable mycobacterium, is undergoing phase III clinical trials as a vaccine against leprosy in India. It has brought about lepromin conversion and histopathological upgradation in a significant number of patients studied so far. It is important to identify antigens of M. w that trigger T-cell responses in leprosy patients vaccinated with this organism. In the present study the peripheral T-cell repertoire of 12 M. w-vaccinated leprosy patients, 10 unimmunized leprosy patients, 8 tuberculoid and 5 healthy contacts was analysed with fractionated antigens of M. w. The lepromatous leprosy patients who are in general anergic to antigens of M. leprae did not respond to antigens of M. w. However, peripheral blood mononuclear cells obtained from leprosy patients who had been vaccinated with M. w responded to many antigens. These responses were frequently directed against low molecular weight entities of 14-45 kDa. T cells from tuberculoid leprosy patients and healthy contacts also responded predominantly to a number of low molecular weight antigens of M. w. The study also identified an immunodominant 28-31 kDa antigenic fraction carrying T- as well as B-cell activating determinants.

Immunotherapeutic effects of a vaccine based on a saprophytic cultivable mycobacterium, Mycobacterium w in multibacillary leprosy patients.

Immunotherapy with a vaccine consisting of autoclaved Mycobacterium w was given in addition to chemotherapy in 54 multibacillary, lepromin negative patients belonging to BB, BL and LL types of leprosy. Thirty-seven patients with similar types of diseases received chemotherapy and placebo injections. The 'vaccine' was repeated every 3 months. Bacterial clearance was more rapid in the vaccinated patients. Two lepromatous leprosy patients with initial bacterial index (BI) of 1.8 and 2.8 became bacteriologically negative in 1 year. One LL patient with BI of 6.0 had a BI fall to 0.16 after four doses of the vaccine. None of the LL patients belonging to placebo group during the same time period became bacteriologically negative. Rapid bacterial clearance was accompanied by distinct signs of clinical improvement. One hundred percent of BB, 85.7% of BL patients and 61.5% of LL patients converted to lepromin positivity after four doses of the vaccine. A significant number of vaccinated patients demonstrated an upgrading in skin lesions histopathologically.