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Unresponsiveness of Mycobacterium w vaccine in managing acute and chronic Leishmania donovani infections in mouse and hamster

Published online by Cambridge University Press:  20 December 2012

RATI TANDON
Affiliation:
Division of Parasitology, CSIR-Central Drug Research Institute, Lucknow-226001, Uttar Pradesh, India
PRAGYA MISRA
Affiliation:
Division of Parasitology, CSIR-Central Drug Research Institute, Lucknow-226001, Uttar Pradesh, India
VISHAL KUMAR SONI
Affiliation:
Division of Parasitology, CSIR-Central Drug Research Institute, Lucknow-226001, Uttar Pradesh, India
NASREEN BANO
Affiliation:
Division of Parasitology, CSIR-Central Drug Research Institute, Lucknow-226001, Uttar Pradesh, India
SHAILJA MISRA-BHATTACHARYA
Affiliation:
Division of Parasitology, CSIR-Central Drug Research Institute, Lucknow-226001, Uttar Pradesh, India
ANURADHA DUBE*
Affiliation:
Division of Parasitology, CSIR-Central Drug Research Institute, Lucknow-226001, Uttar Pradesh, India
*
*Corresponding author: E-mail: anuradha_dube@hotmail.com

Summary

The role of Mycobacterium w (Mw) vaccine as an immunomodulator and immunoprophylactant in the treatment of mycobacterial diseases (leprosy and pulmonary tuberculosis) is well established. The fact that it shares common antigens with leishmanial parasites prompted its assessment as an immunostimulant and as an adjunct to known anti-leishmanials that may help in stimulating the suppressed immune status of Leishmania donovani-infected individuals. The efficacy of Mw vaccine was assessed as an immunomodulator, prophylactically either alone or in combination with anti-leishmanial vaccine, as well as therapeutically as an adjunct to anti-leishmanial treatment in L. donovani-infected hamsters, representing a chronic human Visceral Leishmaniasis (VL) model. Similarly, its efficacy was also evaluated in L. donovani-infected BALB/c mice, representing an acute VL model. The preliminary studies revealed that Mw was ineffective as an immunostimulant and/or immunoprophylactant in hamsters infected with L. donovani, as estimated by T-cell immunological responses. However, in the BALB/c mice-VL model it appeared as an effective immunostimulant but a futile prophylactic agent. It is therefore inferred that, contrary to its role in managing tuberculosis and leprosy infections, Mw vaccine has not been successful in controlling VL infection, emphasizing the need to find detailed explanations for the failure of this vaccine against the disease.

Type
Research Article
Copyright
Copyright © Cambridge University Press 2012

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References

REFERENCES

Adhikari, A., Gupta, G., Majumder, S., Banerjee, S., Bhattacharjee, S., Bhattacharya, P., Kumari, S., Haldar, S., Majumdar, S. B., Saha, B. and Majumdar, S. (2012). Mycobacterium indicus pranii (Mw) re-establishes host protective immune response in Leishmania donovani infected macrophages: critical role of IL-12. PLoS One 7, e40265.CrossRefGoogle ScholarPubMed
Aronson, N. E., Santosham, M., Comstock, G. W., Howard, R. S., Moulton, L. H., Rhoades, E. R. and Harrison, L. H. (2004). Long-term efficacy of BCG vaccine in American Indians and Alaska Natives: A 60-year follow-up study. Journal of the American Medical Association 291, 20862091.CrossRefGoogle ScholarPubMed
Colditz, G. A., Brewer, T. F., Berkey, C. S., Wilson, M. E., Burdick, E., Fineberg, H. V. and Mosteller, F. (1994). Efficacy of BCG vaccine in the prevention of tuberculosis. Meta-analysis of the published literature. Journal of the American Medical Association 271, 698702.CrossRefGoogle ScholarPubMed
Desjeux, P., Piot, B., O'neill, K. and Meert, J. P. (2001). Co-infections of Leishmania/HIV in south Europe. Medecine Tropicale (Marseilles) 61, 187193.Google ScholarPubMed
Ding, A., Nathan, C. F., Graycar, J., Derynck, R., Stuehr, D. J. and Srimal, S. (1990). Macrophage deactivating factor and transforming growth factors-b1, -b2, and -b3 inhibit induction of macrophage nitrogen oxide synthesis by IFN-g. Journal of Immunology 145, 940.CrossRefGoogle Scholar
Fine, P. E. (1995). Variation in protection by BCG: implications of and for heterologous immunity. Lancet, 346, 13391345.CrossRefGoogle ScholarPubMed
Fortier, A. H., Mock, B. A., Meltzer, M. S. and Nacy, C. A. (1987). Mycobacterium bovis BCG-induced protection against cutaneous and systemic Leishmania major infections of mice. Infection and Immunity 55, 17071714.CrossRefGoogle ScholarPubMed
Frommel, D. and Lagrange, P. H. (1989). BCG: a modifier of immune responses to parasites. Parasitology Today 5, 188190.CrossRefGoogle ScholarPubMed
Frommel, D., Ogunkolade, B. W., Vouldoukis, I. and Monjour, L. (1988). Vaccine-induced immunity against cutaneous leishmaniasis in BALB/c mice. Infection and Immunity 56, 843848.CrossRefGoogle ScholarPubMed
Garg, R. and Dube, A. (2006). Animal models for vaccine studies for visceral leishmaniasis. Indian Journal of Medical Research 123, 439454.Google ScholarPubMed
Garg, R., Gupta, S. K., Tripathi, P., Hajela, K., Sundar, S., Naik, S. and Dube, A. (2006). Leishmania donovani: identification of stimulatory soluble antigenic proteins using cured human and hamster lymphocytes for their prophylactic potential against visceral leishmaniasis. Vaccine 24, 29002909.CrossRefGoogle ScholarPubMed
Garg, R., Gupta, S. K., Tripathi, P., Naik, S., Sundar, S. and Dube, A. (2005). Immunostimulatory cellular responses of cured Leishmania-infected patients and hamsters against the integral membrane proteins and non-membranous soluble proteins of a recent clinical isolate of Leishmania donovani. Clinical and Experimental Immunology 140, 149156.CrossRefGoogle ScholarPubMed
Goto, H. and Lindoso, J. A. (2004). Immunity and immunosuppression in experimental visceral leishmaniasis. Brazilian Journal of Medical and Biological Research 37, 615623.CrossRefGoogle ScholarPubMed
Gupta, A., Geetha, N., Mani, J., Upadhyay, P., Katoch, V. M., Natrajan, M., Gupta, U. D. and Bhaskar, S. (2009). Immunogenicity and protective efficacy of ‘Mycobacterium w’ against Mycobacterium tuberculosis in mice immunized with live versus heat-killed Mw by the aerosol or parenteral route. Infection and Immunity 77, 223231.CrossRefGoogle ScholarPubMed
Gupta, R., Kushawaha, P. K., Samant, M., Jaiswal, A. K., Baharia, R. K. and Dube, A. (2011). Treatment of Leishmania donovani-infected hamsters with miltefosine: analysis of cytokine mRNA expression by real-time PCR, lymphoproliferation, nitrite production and antibody responses. Journal of Antimicrobial Chemotherapy 67, 440443.CrossRefGoogle ScholarPubMed
Gupta, S. K., Sisodia, B. S., Sinha, S., Hajela, K., Naik, S., Shasany, A. K. and Dube, A. (2007). Proteomic approach for identification and characterization of novel immunostimulatory proteins from soluble antigens of Leishmania donovani promastigotes. Proteomics 7, 816823.CrossRefGoogle ScholarPubMed
Hart, P. D. and Sutherland, I. (1977). BCG and vole bacillus vaccines in the prevention of tuberculosis in adolescence and early adult life. British Medical Journal 2, 293295.CrossRefGoogle ScholarPubMed
Heldwein, K. A., Liang, M. D., Andresen, T. K., Thomas, K. E., Marty, A. M., Cuesta, N., Vogel, S. N. and Fenton, M. J. (2003). TLR2 and TLR4 serve distinct roles in the host immune response against Mycobacterium bovis BCG. Journal of Leukocyte Biology 74, 277286.CrossRefGoogle ScholarPubMed
Horwitz, M. A. and Harth, G. (2003). A new vaccine against tuberculosis affords greater survival after challenge than the current vaccine in the guinea pig model of pulmonary tuberculosis. Infection and Immunity 71, 16721679.CrossRefGoogle Scholar
Katoch, K., Singh, P., Adhikari, T., Benara, S. K., Singh, H. B., Chauhan, D. S., Sharma, V. D., Lavania, M., Sachan, A. S. and Katoch, V. M. (2008). Potential of Mw as a prophylactic vaccine against pulmonary tuberculosis. Vaccine 26, 12281234.CrossRefGoogle ScholarPubMed
Kehrl, J. H., Wakefield, L. M., Roberts, A. B., Jakowlew, S., Alvarez-Mon, M., Derynck, R., Sporn, M. B. and Fauci, A. S. (1986). Production of transforming growth factor beta by human T lymphocytes and its potential role in the regulation of T cell growth. Journal of Experimental Medicine 163, 10371050.CrossRefGoogle Scholar
Kumari, S., Samant, M., Khare, P., Sundar, S., Sinha, S. and Dube, A. (2008 a). Induction of Th1-type cellular responses in cured/exposed Leishmania-infected patients and hamsters against polyproteins of soluble Leishmania donovani promastigotes ranging from 89·9 to 97·1 kDa. Vaccine 26, 48134818.CrossRefGoogle ScholarPubMed
Kumari, S., Samant, M., Misra, P., Khare, P., Sisodia, B., Shasany, A. K. and Dube, A. (2008 b). Th1-stimulatory polyproteins of soluble Leishmania donovani promastigotes ranging from 89·9 to 97·1 kDa offers long-lasting protection against experimental visceral leishmaniasis. Vaccine 26, 57005711.CrossRefGoogle ScholarPubMed
Misra, A., Dube, A., Srivastava, B., Sharma, P., Srivastava, J. K., Katiyar, J. C. and Naik, S. (2001). Successful vaccination against Leishmania donovani infection in Indian langur using alum-precipitated autoclaved Leishmania major with BCG. Vaccine 19, 34853492.CrossRefGoogle ScholarPubMed
Murray, H. W., Stern, J. J., Welte, K., Rubin, B. Y., Carriero, S. M. and Nathan, C. F. (1987). Experimental visceral leishmaniasis: production of interleukin 2 and interferon-gamma, tissue immune reaction, and response to treatment with interleukin 2 and interferon-gamma. Journal of Immunology 138, 22902297.CrossRefGoogle ScholarPubMed
Noazin, S., Modabber, F., Khamesipour, A., Smith, P. G., Moulton, L. H., Nasseri, K., Sharifi, I., Khalil, E. A., Bernal, I. D., Antunes, C. M., Kieny, M. P. and Tanner, M. (2008). First generation leishmaniasis vaccines: a review of field efficacy trials. Vaccine 26, 67596767.CrossRefGoogle ScholarPubMed
Paciello, O., Wojcik, S., Gradoni, L., Oliva, G., Trapani, F., Iovane, V., Politano, L. and Papparella, S. (2010). Syrian hamster infected with Leishmania infantum: a new experimental model for inflammatory myopathies. Muscle Nerve 41, 355361.CrossRefGoogle ScholarPubMed
Rama Iniguez, S., Dea-Ayuela, M. A., Sanchez-Brunete, J. A., Torrado, J. J., Alunda, J. M. and Bolas-Fernandez, F. (2006). Real-time reverse transcription-PCR quantification of cytokine mRNA expression in golden Syrian hamster infected with Leishmania infantum and treated with a new amphotericin B formulation. Antimicrobial Agents and Chemotherapy 50, 11951201.CrossRefGoogle ScholarPubMed
Rodrigues, V. Jr., Santana Da Silva, J. and Campos-Neto, A. (1998). Transforming growth factor beta and immunosuppression in experimental visceral leishmaniasis. Infection and Immunity 66, 12331236.CrossRefGoogle ScholarPubMed
Samant, M., Gupta, R., Kumari, S., Misra, P., Khare, P., Kushawaha, P. K., Sahasrabuddhe, A. A. and Dube, A. (2009). Immunization with the DNA-encoding N-terminal domain of proteophosphoglycan of Leishmania donovani generates Th1-Type immunoprotective response against experimental visceral leishmaniasis. Journal of Immunology 183, 470479.CrossRefGoogle ScholarPubMed
Sharma, P. A., Srivastava, J. K., Gupta, H. P. and Katiyar, J. C. (1998). Immunization against Leishmania donovani: Efficacy of Mycobacterium habana in combination with killed promastigotes in hamsters. Current Science 74, 770773.Google Scholar
Singh, I. G., Mukherjee, R., Talwar, G. P. and Kaufmann, S. H. (1992). In vitro characterization of T cells from Mycobacterium w-vaccinated mice. Infection and Immunity, 60, 257263.CrossRefGoogle ScholarPubMed
Singh, M., Shakya, S., Soni, V. K., Dangi, A., Kumar, N. and Bhattacharya, S. M. (2009). The n-hexane and chloroform fractions of Piper betle L. trigger different arms of immune responses in BALB/c mice and exhibit antifilarial activity against human lymphatic filarid Brugia malayi. International Journal of Immunopharmacology 9, 716728.CrossRefGoogle ScholarPubMed
Smrkovski, L. L. and Larson, C. L. (1977). Effect of treatment with BCG on the course of visceral leishmaniasis in BALB/c mice. Infection and Immunity 16, 249257.CrossRefGoogle ScholarPubMed
Soni, V. K., Yadav, D. K., Bano, N., Dixit, P., Pathak, M., Maurya, R., Sahai, M., Jain, S. K. and Misra-Bhattacharya, S. (2011). N-methyl-6, 7-dimethoxyisoquinolone in Annona squamosa twigs is the major immune modifier to elicit polarized Th1 immune response in BALB/c mice. Fitoterapia 83, 110116.CrossRefGoogle ScholarPubMed
Srivastava, J. K., Misra, A., Sharma, P., Srivastava, B., Naik, S. and Dube, A. (2003). Prophylactic potential of autoclaved Leishmania donovani with BCG against experimental visceral leishmaniasis. Parasitology 127, 107114.CrossRefGoogle ScholarPubMed
Vedi, S., Dangi, A., Hajela, K. and Misra-Bhattacharya, S. (2008). Vaccination with 73 kDa recombinant heavy chain myosin generates high level of protection against Brugia malayi challenge in jird and mastomys models. Vaccine 26, 59976005.CrossRefGoogle Scholar
Villarreal-Ramos, B. (2009). Towards improved understanding of protective mechanisms induced by the BCG vaccine. Expert Review of Vaccines 8, 15311534.CrossRefGoogle ScholarPubMed
Von Meyenn, F., Schaefer, M., Weighardt, H., Bauer, S., Kirschning, C. J., Wagner, H. and Sparwasser, T. (2006). Toll-like receptor 9 contributes to recognition of Mycobacterium bovis Bacillus Calmette-Guerin by Flt3-ligand generated dendritic cells. Immunobiology 211, 557565.CrossRefGoogle ScholarPubMed
Wadhone, P., Maiti, M., Agarwal, R., Kamat, V., Martin, S. and Saha, B. (2009). Miltefosine promotes IFN-gamma-dominated anti-leishmanial immune response. Journal of Immunology 182, 71467154.CrossRefGoogle ScholarPubMed
Weintraub, J. and Weinbaum, F. I. (1977). The effect of BCG on experimental cutaneous leishmaniasis in mice. Journal of Immunology 118, 22882290.CrossRefGoogle ScholarPubMed
Wilson, M. E., Jeronimo, S. M. and Pearson, R. D. (2005). Immunopathogenesis of infection with the visceralizing Leishmania species. Microbial Pathogenesis 38, 147160.CrossRefGoogle ScholarPubMed
Zaheer, S. A., Mukherjee, R., Ramkumar, B., Misra, R. S., Sharma, A. K., Kar, H. K., Kaur, H., Nair, S., Mukherjee, A. and Talwar, G. P. (1993). Combined multidrug and Mycobacterium w vaccine therapy in patients with multibacillary leprosy. Journal of Infectious Diseases 167, 401410.CrossRefGoogle ScholarPubMed
Zurgil, N., Shafran, Y., Afrimzon, E., Fixler, D., Shainberg, A. and Deutsch, M. (2006). Concomitant real-time monitoring of intracellular reactive oxygen species and mitochondrial membrane potential in individual living promonocytic cells. Journal of Immunological Methods 316, 2741.CrossRefGoogle ScholarPubMed