Mycobacterium indicus pranii vaccine immunoprophylaxis in anti-phenolic glycolipid-1-positive leprosy contacts – A pilot study from a tertiary care center in North India

Background: Contacts of leprosy patients have an increased risk of infection with Mycobacterium leprae. Contact tracing and chemo- or immunoprophylaxis are important means of preventing leprosy transmission. Aims: We aimed to evaluate the efficacy of immunoprophylaxis with Mycobacterium indicus pranii vaccine in reducing anti-phenolic glycolipid-1 titers in household contacts of leprosy patients. Methods: This prospective single-center study was conducted in a tertiary care center in North India from January 2015 to December 2016. Contacts of leprosy patients (both paucibacillary and multibacillary) were screened for anti-phenolic glycolipid-1 antibodies with enzyme-linked immunosorbent assay. Those found positive were given immunoprophylaxis with a single dose of Mycobacterium indicus pranii vaccine, and anti-phenolic glycolipid-1 titers were evaluated at six and 12 months. All contacts were clinically followed for three years. Results: Of the 135 contacts of 98 leprosy patients that were screened, 128 were recruited. Seventeen of these contacts were positive for anti-phenolic glycolipid-1 antibodies and were given Mycobacterium indicus pranii vaccine. Two contacts were lost to follow-up. After immunoprophylaxis, anti-phenolic glycolipid-1 titers were negative in all patients at all intervals, and no contact developed any clinical signs or symptoms of leprosy during the three-year follow-up. Limitations: The small number of contacts studied, the short follow-up period and the absence of a control group were limitations of this study. Dicussion: We could not find any papers on natural decline of PGL 1 titres in contacts, although in leprosy patients, these titres may even increase after completion of treatment. However the titres do correlate with bacterial load (reference: Int J Lepr Other Mycobact Dis. 1998 Sep;66(3):356-64) so if the tires decrease or become negative it may be considered as an indirect evidence of bacillary clearance. Hence we may suggest the protective efficacy. Furthermore, as the editor mentioned, considering the small number of positive patients, a control group was not possible in the present pilot study, but such studies may be carried out in the future. Conclusion: Immunoprophylaxis with Mycobacterium indicus pranii vaccine is effective and safe in preventing disease in contacts of leprosy patients. However, these findings need to be replicated in larger studies.

Leprosy vaccines – A voyage unfinished

Leprosy, a chronic granulomatous disease caused by Mycobacterium leprae, is endemic in many regions of the world. With introduction of multidrug therapy in 1982, there has been a dramatic reduction in the prevalence of leprosy, but new cases continue to appear. There have been more than 200,000 new cases per year for the past 10 years. There is a renewed interest in leprosy vaccines with immunoprophylactic and immunotherapeutic roles. Due to the difficulty in cultivating M. leprae in artificial media, vaccine strategies have centered on the use of cross-sensitizing mycobacteria. Bacillus Calmette–Guerin (BCG) has been the most popular among these, but with a widely varying protective efficacy reported from different parts of the world. In three meta-analyses, BCG has shown strong evidence of efficacy against leprosy. Recently, India has focused interest on another vaccine, Mycobacterium indicus pranii vaccine earlier known as Mycobacterium w. To overcome the limitations of these whole cell vaccines, various recombinant BCGs and subunit vaccines have been developed and studied in experimental models. These often yield inconsistent results. However, a new subunit recombinant vaccine – LepVax holds promise and has completed Phase 1a clinical trials successfully.

An Immunotherapeutic Vaccine Originally Developed Against Leprosy Is Effective Not Only Against Leprosy But Also Against Tuberculosis, Ano-genital Warts and Some Cancers – A Potent Invigorator of Immune Response

Based on atypical cultivable non-pathogenic mycobacteria, a vaccine with immunoprophylactic cum immuno-therapeutic properties against leprosy was developed by us many years back. The gene sequence of Mw (code word) is now known and it has been named as Mycobacterium indicus pranii (MIP). Besides Leprosy, MIP has also remarkable capabilities for treatment of tuberculosis including category II, “Difficult to treat” tuberculosis. What is further impressive is its ability to cure ugly ano-genital warts. It has therapeutic action against Myelomas. MIP activated T cells and cytokines, particularly ƴ-interferon play a major role in action of MIP against cancer cells. Combination of MIP with cyclophosphamide improves anti-tumour activity. MIP is a potent invigorator of immune responses and is being employed as an adjuvant in a potential Birth Control Vaccine against hCG, currently under development. MIP is approved by the Drugs Controller General of India & US FDA. It is licensed to a company for availability to public in India and elsewhere in the world. Very recently, a trial has been launched by CSIR, Ministry of Science and Technology on the utility of Mw (MIP) to cure those individuals who are infected with Corona and protect family members if possible by immuno-prophylaxis.

Combination of Mycobacterium indicus pranii and Heat-Induced Promastigotes Cures Drug-Resistant Leishmania Infection: Critical Role of Interleukin-6-Producing Classical Dendritic Cells

ABSTRACT The major issues in available therapeutic modalities against leishmaniasis are cost, toxicity, and the emergence of drug resistance. The aim of this work was to develop a successful therapeutic adjuvant against drug-resistant Leishmania donovani infection by means of combining Mycobacterium indicus pranii with heat-induced promastigotes (HIP). One-month postinfected BALB/c mice were administered subcutaneously with M. indicus pranii (108 cells) and HIP (100 μg) for 5 days. Spleens were harvested for flow cytometric and reverse transcriptase PCR analysis. The antileishmanial effect of the combination strategy was associated with induction of a disease-resolving Th1 and Th17 response with simultaneous downregulation of CD4+ CD25+ Foxp3+ (nTreg) cells and CD4+ CD25− Foxp3− (Tr1) cells in the spleen. The significant expansion of CD4+ TCM (CD4+ CD44hi CD11ahi CD62Lhi) cells was a further interesting outcome of this therapeutic strategy in the context of long-term protection of hosts against secondary infection. Toll-like receptor 2 (TLR2) was also found instrumental in this antiparasitic therapy. Induced interleukin-6 (IL-6) production from expanded CD11c+ CD8α+ (cDC1) and CD11c+ CD11b+ (cDC2) dendritic cells (DCs) but not from the CD11b+ Ly6c+ inflammatory monocytes (iMOs), was found critical in the protective expansion of Th17 as evidenced by an in vivo IL-6 neutralization assay. It also promoted the hematopoietic conversion toward DC progenitors (pre-DCs) from common dendritic cell progenitors (CDPs), the immediate precursors, in bone marrow. This novel combinational strategy demonstrated that expansion of Th17 by IL-6 released from CD11c+ classical DCs is crucial, together with the conventional Th1 response, to control drug-resistant infection.