Recombinant Leishmania tarentolae expressing the A2 virulence gene as a novel candidate vaccine against visceral leishmaniasis |
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Authors: | Amir Mizbani Tahereh Taheri Farnaz Zahedifard Yasaman Taslimi Hiva Azizi Kayhan Azadmanesh Barbara Papadopoulou Sima Rafati |
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Institution: | 1. Molecular Immunology and Vaccine Research Laboratory, Pasteur Institute of Iran, Tehran, Iran;2. Department of Biotechnology, University College of Science, University of Tehran, Tehran, Iran;3. Hepatitis and AIDS Department, Pasteur Institute of Iran, Tehran, Iran;4. Research Centre in Infectious Diseases, CHUL Research Centre and Department of Microbiology and Immunology, Faculty of Medicine, Laval University, 2705 Laurier Blvd., Quebec (QC), Canada G1V 4G2 |
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Abstract: | Visceral leishmaniasis is the most severe form of leishmaniasis. To date, there is no effective vaccine against this disease. Many antigens have been examined so far as protein- or DNA-based vaccines, but none of them conferred complete long-term protection. The use of live attenuated vaccines has recently emerged as a promising vaccination strategy. In this study, we stably expressed the Leishmania donovani A2 antigen in Leishmania tarentolae, a non-pathogenic member of the genus Leishmania, and evaluated its protective efficacy as a live vaccine against L. infantum challenge. Our results show that a single intraperitoneal administration of the A2-recombinant L. tarentolae strain protects BALB/c mice against L. infantum challenge and that protective immunity is associated with high levels of IFN-γ production prior and after challenge. This is accompanied by reduced levels of IL-5 production after challenge, leading to a potent Th1 immune response. In contrast, intravenous injection elicited a Th2 type response, characterized by higher levels of IL-5 and high humoral immune response, resulting in a less efficient protection. All together, these results indicate the promise of A2-expressing L. tarentolae as a safe live vaccine against visceral leishmaniasis. |
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Keywords: | Visceral leishmaniasis Recombinant Leishmania tarentolae Live vaccine A2 gene Immune response |
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