Intracellular replication-deficient Leishmania donovani induces long lasting protective immunity against visceral leishmaniasis.

Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA.
The Journal of Immunology (Impact Factor: 5.36). 09/2009; 183(3):1813-20. DOI: 10.4049/jimmunol.0900276
Source: PubMed

ABSTRACT No vaccine is currently available for visceral leishmaniasis (VL) caused by Leishmania donovani. This study addresses whether a live attenuated centrin gene-deleted L. donovani (LdCen1(-/-)) parasite can persist and be both safe and protective in animals. LdCen1(-/-) has a defect in amastigote replication both in vitro and ex vivo in human macrophages. Safety was shown by the lack of parasites in spleen and liver in susceptible BALB/c mice, immune compromised SCID mice, and human VL model hamsters 10 wk after infection. Mice immunized with LdCen1(-/-) showed early clearance of virulent parasite challenge not seen in mice immunized with heat killed parasites. Upon virulent challenge, the immunized mice displayed in the CD4(+) T cell population a significant increase of single and multiple cytokine (IFN-gamma, IL-2, and TNF) producing cells and IFN-gamma/IL10 ratio. Immunized mice also showed increased IgG2a immunoglobulins and NO production in macrophages. These features indicated a protective Th1-type immune response. The Th1 response correlated with a significantly reduced parasite burden in the spleen and no parasites in the liver compared with naive mice 10 wk post challenge. Protection was observed, when challenged even after 16 wk post immunization, signifying a sustained immunity. Protection by immunization with attenuated parasites was also seen in hamsters. Immunization with LdCen1(-/-) also cross-protected mice against infection with L. braziliensis that causes mucocutaneous leishmaniasis. Results indicate that LdCen1(-/-) can be a safe and effective vaccine candidate against VL as well as mucocutaneous leishmaniasis causing parasites.

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    ABSTRACT: Leishmania and Leptomonas are protozoan parasites of the family Trypanosomatidae. Leishmania donovani causes the fatal visceral leishmaniasis (VL; kala-azar) in mammals and is transmitted by sand fly vector. Certain VL-cured human populations in India and Sudan develop post kala-azar dermal leishmaniasis (PKDL) due to the same parasite. Although Leptomonas is parasitic mainly in insects, several recent reports on the clinical isolates of L. donovani from VL and PKDL patients in India confirm co-infection of Leptomonas seymouri, probably due to immune suppression in those individuals. Detection of L. seymouri in the in vitro cultures of L. donovani from clinical origin is difficult due to many similarities between L. seymouri and L. donovani. We describe here ways to detect L. seymouri and L. donovani in co-culture. In addition, based on our observation regarding the growth of L. seymouri in different culture conditions, we report here a novel procedure, which can selectively eliminate L. seymouri from the in vitro co-culture with L. donovani. This would be beneficial to researchers who prefer to deal with pure population of Leishmania parasites for various downstream immunological and genetic studies. Copyright © 2015. Published by Elsevier Ireland Ltd.
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