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Current Status and Future Challenges for the Development of Genetically Altered Live Attenuated Leishmania Vaccines

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Book cover Pathogenesis of Leishmaniasis

Abstract

Leishmaniasis is a protozoan parasitic disease endemic to the tropical and subtropical regions of the world, with three major clinical forms, self-healing cutaneous leishmaniasis, mucocutaneous leishmaniasis, and fatal visceral leishmaniasis (VL). Drug treatment is expensive, and often results in the development of resistance due to lack of compliance and prolonged use. No vaccine is available against leishmaniasis. Immunization with first- and second-generation Leishmania vaccines has shown some efficacy in animal models but little or none in humans. However, individuals who recover from a natural infection are protected from reinfection and develop lifelong protection, suggesting infection may be a prerequisite for creating immunological memory. Genetically altered live attenuated parasites with controlled infectivity could achieve such immunological memory and yield protection without overt disease. In this chapter, we discuss development and characteristics of genetically altered live attenuated Leishmania donovani parasites and their possible use as vaccine candidates against VL. In addition, we discuss the challenges with regard to safety and immunogenicity of the live attenuated parasites.

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Acknowledgements

We thank Drs. Alain Debrabant and Sanjai Kumar (DETTD, CBER/FDA) for critical review of the manuscript. This work was supported by intramural funds of the Center for Biologics Evaluation and Research, FDA.

Disclaimer The findings of this study are an informal communication and represent authors’ own best judgment. These comments do not bind or obligate the Food and Drug Administration.

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Authors and Affiliations

  1. Division of Emerging and Transfusion Transmitted Diseases, Office of Blood Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD, 20892, USA

    Ranadhir Dey, Sreenivas Gannavaram, Jacqueline Fiuza, Robert Duncan & Hira L. Nakhasi

  2. Institute of Molecular Medicine, 254 Okhla Industrial Estate, Phase III, New Delhi, 110020, India

    Angamuthu Selvapandiyan

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  1. Ranadhir Dey
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  2. Sreenivas Gannavaram
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  3. Angamuthu Selvapandiyan
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  4. Jacqueline Fiuza
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  5. Robert Duncan
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  6. Hira L. Nakhasi
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Correspondence to Hira L. Nakhasi .

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Editors and Affiliations

  1. Department of Pathology, The Ohio State University, Columbus, Ohio, USA

    Abhay Satoskar

  2. Department of Internal Medicine, University of New Mexico, Albuquerque, New Mexico, USA

    Ravi Durvasula

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Dey, R., Gannavaram, S., Selvapandiyan, A., Fiuza, J., Duncan, R., Nakhasi, H.L. (2014). Current Status and Future Challenges for the Development of Genetically Altered Live Attenuated Leishmania Vaccines. In: Satoskar, A., Durvasula, R. (eds) Pathogenesis of Leishmaniasis. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-9108-8_4

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