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Therapeutic immunization with radio-attenuated Leishmania parasites through i.m. route revealed protection against the experimental murine visceral leishmaniasis

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Abstract

After our promising results from prophylactic and therapeutic study (i.p. route) with the radio-attenuated Leishmania donovani parasites against experimental murine visceral leishmaniasis, we prompted to check their therapeutic efficacy through i.m route. BALB/c mice were infected with highly virulent L. donovani parasites. After 75 days, mice were treated with gamma (γ)-irradiated parasites. A second therapeutic immunization was given after 15 days of first immunization. The protection against kala-azar was estimated with the reduction of Leishman–Donovan unit from spleen and liver that scored up to 80% and 93%, respectively, while a twofold increase in nitric oxide (NO) and reactive oxygen species (ROS) productions has been observed in the immunized groups of animals. These groups of mice also showed disease regression by skewing Th2 cytokines (IL-10) towards Th1 cytokine (IFN-γ) bias along with the increased generation of NO and ROS, while the infected control group of mice without such treatment surrendered to the disease. Establishment of Th1 ambience in the treated groups has also been supported from the measured antileishmanial antibody IgG subsets (IgG2a and IgG1) with higher anti-soluble Leishmania antigen-specific IgG2a titer. As seen in our previous studies, doses of attenuation by γ-radiation should be taken into serious consideration. Attenuation of parasites at 50 Gy of absorbed dose of gamma rays has not worked well. Thus, therapeutic use of L. donovani parasites radio-attenuated at particular doses can be exploited as a promising vaccine agent. Absence of any adjuvant may increase its acceptability as vaccine candidate further.

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Acknowledgments

The authors sincerely acknowledge UGC-DAE Consortium for Scientific Research, Kolkata Centre, Kolkata and Council for Scientific and Industrial Research (CSIR), India for the financial help. Sanchita Datta is SRF, CSIR. The authors also express their gratitude to Kshudiram Naskar, Infectious Diseases and Immunology Laboratory, Indian Institute of Chemical Biology, Kolkata for his kind cooperation and help. For the infrastructure help, the cooperation of Director of Public Instructions, Govt. of West Bengal, India and Officer in Charge, Bethune College, Kolkata is duly acknowledged.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Zoology, Bethune College, 181, Bidhan Sarani, Kolkata, 700006, India

    Sanchita Datta, Madhumita Manna & Supriya Khanra

  2. Infectious Diseases and Immunology, Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Kolkata, 700032, India

    Moumita Ghosh & Syamal Roy

  3. Department of Instrumentation Science, Jadavpur University, 188 Raja S.C. Mullick Road, Kolkata, 700032, India

    Radhaballav Bhar

  4. UGC-DAE Consortium for Scientific Research, 3/LB-8, Salt Lake, Kolkata, 700098, India

    Anindita Chakraborty

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  1. Sanchita Datta
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  2. Madhumita Manna
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Correspondence to Madhumita Manna.

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Datta, S., Manna, M., Khanra, S. et al. Therapeutic immunization with radio-attenuated Leishmania parasites through i.m. route revealed protection against the experimental murine visceral leishmaniasis. Parasitol Res 111, 361–369 (2012). https://doi.org/10.1007/s00436-012-2847-4

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