Preclinical validation of a live attenuated dermotropic Leishmania vaccine against vector transmitted fatal visceral leishmaniasis
| Autor: | Shaden Kamhawi, Wen Wei Zhang, Telly Sepahpour, Fabiano Oliveira, Krishna Pandey, Shinjiro Hamano, Timur Oljuskin, Jesus G. Valenzuela, Swarnendu Kaviraj, Subir Karmakar, James Oristian, Sanika Satoskar, Claudio Meneses, Nevien Ismail, Sreenivas Gannavaram, Ranadhir Dey, Pradeep Das, Abhishek Mondal, Parna Bhattacharya, Kamaleshwar P Singh, Abhay R. Satoskar, Greg Matlashewski, Rajiv M Sastry, Greta Volpedo, Sushmita Das, Monika Satoskar, Sanjay Singh, Hira L. Nakhasi |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Live attenuated vaccines QH301-705.5 Genes Protozoan Leishmania donovani Protozoan Proteins Medicine (miscellaneous) Spleen Vaccines Attenuated General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences 0302 clinical medicine Immune system parasitic diseases medicine Leishmania major Intradermal injection Biology (General) Leishmaniasis Vaccines biology Immunogenicity biology.organism_classification medicine.disease Leishmania Virology 030104 developmental biology medicine.anatomical_structure Visceral leishmaniasis Leishmaniasis Visceral General Agricultural and Biological Sciences Gene Deletion 030215 immunology |
| Zdroj: | Communications Biology Communications Biology, Vol 4, Iss 1, Pp 1-14 (2021) |
| ISSN: | 2399-3642 |
| Popis: | Visceral Leishmaniasis (VL), a potentially fatal disease is caused by Leishmania donovani parasites with no vaccine available. Here we produced a dermotropic live attenuated centrin gene deleted Leishmania major (LmCen−/−) vaccine under Good Laboratory Practices and demonstrated that a single intradermal injection confers robust and durable protection against lethal VL transmitted naturally via bites of L. donovani-infected sand flies and prevents mortality. Surprisingly, immunogenicity characteristics of LmCen−/− parasites revealed activation of common immune pathways like L. major wild type parasites. Spleen cells from LmCen−/− immunized and L. donovani challenged hamsters produced significantly higher Th1-associated cytokines including IFN-γ, TNF-α, and reduced expression of the anti-inflammatory cytokines like IL-10, IL-21, compared to non-immunized challenged animals. PBMCs, isolated from healthy people from non-endemic region, upon LmCen−/− infection also induced more IFN-γ compared to IL-10, consistent with our immunogenicity data in LmCen−/− immunized hamsters. This study demonstrates that the LmCen−/− parasites are safe and efficacious against VL and is a strong candidate vaccine to be tested in a human clinical trial. Karmakar et al produced a dermotropic, live attenuated centrin gene-deleted Leishmania major (LmCen−/−) vaccine against Visceral Leishmaniasis (VL). They demonstrated in hamsters that a single intradermal injection confers robust and durable protection against lethal VL that is transmitted naturally via bites of L. donovani-infected sand flies. |
| Databáze: | OpenAIRE |
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