Hostname: page-component-76fb5796d-dfsvx Total loading time: 0 Render date: 2024-04-26T23:48:29.274Z Has data issue: false hasContentIssue false
  • English
  • Français

Studies on the protective efficacy of second-generation vaccine along with standard antileishmanial drug in Leishmania donovani infected BALB/c mice

Published online by Cambridge University Press:  26 November 2013

JYOTI JOSHI  and
SUKHBIR KAUR
JYOTI JOSHI
Affiliation:
Department of Zoology, Panjab University, Chandigarh 160014, India
SUKHBIR KAUR*
Affiliation:
Department of Zoology, Panjab University, Chandigarh 160014, India
*
*Corresponding author: Parasitology Laboratory, Department of Zoology, Panjab University, Chandigarh 160014, India. E-mail: puzoology@yahoo.com
Get access Rights & Permissions [Opens in a new window]

Summary

It is well established that visceral leishmaniasis (VL; also known as Kala azar) causes immunosuppression, and a successful drug treatment is associated with the development of cell-mediated immunity. Therefore combining a drug with an immune enhancer can provide a better approach for the treatment of the disease. Keeping this in mind, the in vivo antileishmanial efficacy of immunochemotherapy was evaluated with the use of a 78 kDa antigen with or without monophosphoryl lipid A (MPL-A) along with a traditional drug sodium stibogluconate (SSG) in Leishmania donovani infected BALB/c mice. Mice were infected intracardially with promastigotes of L. donovani, and 30 days after infection, these animals were given specific immunotherapy (78 kDa/78 kDa+MPL-A) or chemotherapy (SSG) or immunochemotherapy (SSG+78 kDa/SSG+78 kDa+MPL-A). Animals were euthanased on 1, 15 and 30 post-treatment days. The antileishmanial potential of the immunochemotherapy was revealed by significant reduction in the parasite burden (P<0·001). These animals were also found to exhibit increased delayed type hypersensitivity (DTH) responses, higher IgG2a levels, lower IgG1 levels and greater cytokine (IFN-γ and IL-2) concentrations compared with chemotherapy or immunotherapy alone, pointing towards the generation of a strong protective (Th1) type of immune response. Immunochemotherapy with SSG+78 kDa+MPL-A was found to be most effective in protecting mice against VL and therefore can be an alternative option for treatment of VL.

Keywords

Visceral leishmaniasisimmunochemotherapysodium stibogluconate78 kDa antigenMPL-A
Type
Research Article
Information
Parasitology , Volume 141 , Issue 4 , April 2014 , pp. 554 - 562
Copyright
Copyright © Cambridge University Press 2013 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Awasthi, A., Mathur, R. K. and Saha, B. (2004). Immune response to Leishmania infection. Indian Journal of Medical Research 119, 238–258.Google Scholar
Banerjee, A., De, M. and Ali, N. (2008). Complete cure of experimental visceral Leishmaniasis with Amphotericin B in Stearylamine-bearing cationic liposomes involves down-regulation of IL-10 and favorable T cell responses. Journal of Immunology 181, 1386–1398.Google Scholar
Borja-Cabrera, G. P., Santos, F. N., Santos, F. B., Trivellato, F. A., Kawasaki, J. K., Costa, A. C., Castro, T., Nogueira, F. S., Moreira, M. A., Luvizotto, M. C., Palatnik, M. and Palatnik-de-Sousa, C. B. (2010). Immunotherapy with the saponin enriched-Leishmune vaccine versus immunochemotherapy in dogs with natural canine visceral leishmaniasis. Vaccine 28, 597–603. doi: 10.1016/j.vaccine.2009.09.071.CrossRefGoogle ScholarPubMed
Bradley, D. J. and Kirkley, J. (1977). Regulation of Leishmania population within host 1. The variable course of L. donovani infections in mice. Clinical Experimental Immunology 30, 119–129.Google Scholar
Dey, R., Dagur, P. K., Selvapandiyan, A., McCoy, J. P., Salotra, P., Duncan, R. and Nakhasi, H. L. (2013). Live attenuated Leishmania donovani p27 gene knockout parasites are nonpathogenic and elicit long-term protective immunity in BALB/c Mice. Journal of Immunology 190, 2138–2149. doi: 10.4049/jimmunol.1202801.Google Scholar
Freitas-Junior, L. H., Chatelain, E., Kim, H. A. and Siqueira-Neto, J. L. (2012). Visceral leishmaniasis treatment: what do we have, what do we need and how to deliver it? International Journal of Parasitology: Drugs and Drug Resistance 2, 11–19. doi: 10.1016/j.bbr.2011.03.031.Google Scholar
Gorak, P. M., Engwerda, C. R. and Kaye, P. M. (1998). Dendritic cells, but not macrophages, produce IL-12 immediately following Leishmania donovani infection. European Journal of Immunology 28, 687–695. doi: 10.1002/(SICI)1521-4141(199802)28:02<687::AID-IMMU687>3.0.CO;2-N.Google Scholar
Gustafson, G. L. and Rhodes, M. J. (1994). Effects of tumor necrosis factor and dexamethasone on the regulation of interferon-gamma induction by monophosphoryl lipid A. Journal of Immunotherapy with Emphasis on Tumor Immunology: Official Journal of the Society for the Biological Therapy 15, 129–133. doi: 10.1097/00002371-199402000-00006.Google Scholar
Hamid, M. N., Simin, S. K. and Davood, I. (2007). Leishmania tropica infection in comparison to Leishmania major induces lower delayed type hypersensitivity in BALB/c mice. Korean Journal of Parasitology 45, 103–109. doi: 10.3347/kjp.2007.45.2.103.Google Scholar
Handman, E. (2001). Leishmaniasis: current status of vaccine development. Clinical Microbiology Reviews 14, 229–243. doi: 10.1128/CMR.14.2.229-243.2001.Google Scholar
Jonuleit, H., Knop, J. and Enk, A. H. (1996). Cytokines and their effects on maturation, differentiation and migration of dendritic cells. Archives of Dermatological Research 289, 1–8. doi: 10.1007/s004030050144.CrossRefGoogle ScholarPubMed
Kaur, S., Kaur, T., Garg, N., Mukherjee, S., Raina, P. and Athokpam, V. (2008). Effect of dose and route of inoculation on the generation of CD4+ Th1/Th2 type of immune response in murine visceral leishmaniasis. Parasitology Research 103, 1413–1419. doi: 10.1007/s00436-008-1150-x.Google Scholar
Kaur, S., Sachdeva, H., Dhuria, S., Sharma, M. and Kaur, T. (2010). Antileishmanial effect of cisplatin against murine visceral leishmaniasis. Parasitology International 59, 62–69. doi: 10.1016/j.parint.2009.10.006.Google Scholar
Kaye, P. M. (1987). Acquisition of cell-mediated immunity to Leishmania. I. Primary T-cell activation detected by IL-2 receptor expression. Immunology 61, 345–349.Google Scholar
Khabiri, A. R., Bagheri, F. and Assmar, M. (2007). Leishmania major common antigen responsible for induction of delayed-type-hypersensitivity response in guinea pigs. Parasitology Research 100, 629–632. doi: 10.1007/s00436-006-0301-1.Google Scholar
Mayrink, W., Magalhaes, P. A., Michalick, M. S. M., da Costa, C. A., Oliveira, L. A., Melo, M. N., Toledo, V. P., Nascimento, E., Dias, M., Genaro, O., Hermeto, M. V. and Williams, P. (1992). Immunotherapy as a treatment of American cutaneous leishmaniasis: preliminary studies in Brazil. Parasitologia 34, 159–165.Google Scholar
Mayrink, W., Botelho, A. C., Magalhaes, P. A., Batista, S. M., Lima, A. O., Genaro, O., Costa, C. A., Melo, M. N., Michalick, M. S., Williams, P., Dias, M., Caiaffa, W. T., Nascimento, Ed. and Machado-Coelho, G. L. (2006). Immunotherapy, immunochemotherapy and chemotherapy for American cutaneous leishmaniasis treatment. Revista da Sociededa Brasileira de Medicina Tropical 39, 14–21.Google Scholar
McCall, L-I., Zhang, W-W. and Matlashewski, G. (2013). Determinants for the development of visceral leishmaniasis disease. PLoS Pathogens 9, e1003053. doi: 10.1371/journal.ppat.1003053.Google Scholar
Melby, P. C., Tabares, A., Restrepo, B. I., Cardona, A. E., McGuff, H. S. and Teale, J. M. (2001). Leishmania donovani: evaluation and architecture of the splenic cellular immune response related to control of infection. Experimental Parasitology 99, 17–25.Google Scholar
Modabber, F. (2010). Leishmaniasis vaccines: past, present and future. International Journal of Antimicrobial Agents 36, S58–S61. doi: 10.1016/j.ijantimicag.2010.06.024.Google Scholar
Murray, H. W., Berman, J. D. and Wright, S. D. (1988). Immunochemotherapy for intracellular Leishmania donovani infection: gamma interferon plus pentavalent antimony. Journal of Infectious Diseases 157, 973–978. doi: 10.1093/infdis/157.5.973.CrossRefGoogle ScholarPubMed
Murray, H. W., Brooks, E. B., DeVecchio, J. L. and Heinzel, F. P. (2003). Immunoenhancement combined with amphotericin B as treatment for experimental visceral leishmaniasis. Antimicrobial Agents Chemotherapy 47, 2513–2517. doi: 10.1128/AAC.47.8.2513-2517.2003.CrossRefGoogle ScholarPubMed
Musa, A. M., Khalil, E. A., Mahgoub, F. A., Elgawi, S. H., Modabber, F., Elkadaru, A. E., Aboud, M. H., Noazin, S., Ghalib, H. W. and El-Hassan, A. M. (2008). Immunochemotherapy of persistent post-kala-azar dermal leishmaniasis: a novel approach to treatment. Transactions of Royal Society of Tropical Medicine and Hygiene 102, 58–63. doi: 10.1016/j.trstmh.2007.08.006.Google Scholar
Nabors, G. S., Afonso, L. C., Farrell, J. P. and Scott, P. (1995). Switch from a type 2 to a type 1T helper cell response and cure of established Leishmania major infection in mice is induced by combined therapy with interleukin-12 and Pentostam. Proceedings of the National Academy of Sciences USA 92, 3142–3146.Google Scholar
Nagill, R. and Kaur, S. (2010). Enhanced efficacy and immunogenicity of 78 kDa antigen formulated in various adjuvants against murine visceral leishmaniasis. Vaccine 28, 4002–4012. doi: 10.1016/j.vaccine.2010.01.015.Google Scholar
Nagill, R. and Kaur, S. (2011). Vaccine candidates for leishmaniasis: a review. International Immunopharmacology 11, 1464–1488. doi: 10.1016/j.intimp.2011.05.008.CrossRefGoogle ScholarPubMed
Rao, R. R., Mahajan, R. C. and Ganguly, N. K. (1984). Modified media for in vitro cultivation of Leishmania promastigotes. A comparative study. P G I Bulletin 18, 125–128.Google Scholar
Ribi, E., Cantrell, J. L., Takayama, K., Qureshi, N., Peterson, J. and Ribi, H. O. (1984). Lipid A and immunotherapy. Clinical Infectious Diseases 6, 567–584. doi: 10.1093/clinids/6.4.567.Google Scholar
Roberts, M. T. M. (2006). Current understanding on the immunology of leishmaniasis and recent developments in prevention and treatment. British Medical Bulletin 75–76, 115–130. doi: 10.1093/bmb/ldl003.Google Scholar
Sharma, M., Sehgal, R. and Kaur, S. (2012). Evaluation of nephroprotective and immunomodulatory activities of antioxidants in combination with cisplatin against murine visceral leishmaniasis. Plos Neglected Tropical Diseases 6, e1629. doi: 10.1371/journal.pntd.0001629.CrossRefGoogle ScholarPubMed
Sodhi, S., Kaur, S., Mahajan, R. C., Ganguly, N. K. and Malla, N. (1992). Effect of sodium stibogluconate and pentamidine on in vitro multiplication of Leishmania donovani in peritoneal macrophages from infected and drug- treated BALB/c mice. Immunology Cell Biology 70, 25–31. doi: 10.1038/icb.1992.4.Google Scholar
Stanley, A. C., Zhou, Y., Amante, F. H., Randall, L. M., Haque, A., Pellicci, D. G., Hill, G. R., Smyth, M. J., Godfrey, D. I. and Engwerda, C. R. (2008). Activation of invariant NKT cells exacerbates experimental visceral leishmaniasis. PLoS Pathogens 4, e1000028. doi: 10.1371/journal.ppat.1000028.Google Scholar
Sundar, S., Singh, V. P., Sharma, S., Makharia, M. K. and Murray, H. W. (1997). Response to interferon-γ plus pentavalent antimony in Indian visceral leishmaniasis. Journal of Infectious Diseases 176, 1117–1119. doi: 10.1086/516526.Google Scholar
Tripathi, P., Chandra, D. and Naik, S. (2008). Immunomodulatory effect of antigenic fractions of recent clinical isolate of L. donovani on monocytic cell lines. Central European Journal of Immunology 33, 1–7.Google Scholar