Preclinical validation of a second generation leishmanization vaccine against vector transmitted fatal visceral leishmaniasis Article Swipe
Subir Karmakar
,
Nevien Ismail
,
Fabiano Oliveira
,
James Oristian
,
Wen‐Wei Zhang
,
Swarnendu Kaviraj
,
Kamaleshwar P. Singh
,
Abhishek Mondal
,
Sushmita Das
,
Krishna Pandey
,
Parna Bhattacharya
,
Greta Volpedo
,
Sreenivas Gannavaram
,
Monika Satoskar
,
Sanika Satoskar
,
Rajiv M. Sastry
,
Claudio Meneses
,
Shinjiro Hamano
,
Pradeep Das
,
Greg Matlashewski
,
Sanjay Singh
,
Shaden Kamhawi
,
Ranadhir Dey
,
Jesús G. Valenzuela
,
Abhay R. Satoskar
,
Hira L. Nakhasi
·
YOU?
·
· 2020
· Open Access
·
· DOI: https://doi.org/10.1101/2020.11.18.388553
YOU?
·
· 2020
· Open Access
·
· DOI: https://doi.org/10.1101/2020.11.18.388553
Visceral Leishmaniasis (VL) is fatal if untreated. There is no licensed vaccine available against human leishmaniasis. We recently demonstrated protection in mice against L. major infection using a CRISPR genome edited attenuated Leishmania major strain ( LmCen −/− ). Here, as a pre-clinical step, we evaluated the protective efficacy of LmCen −/− against VL induced by sand fly transmitted Leishmania donovani in hamsters. Intradermal immunization of hamsters with LmCen −/− did not develop any lesion; while still priming a pro-inflammatory immune response. When challenged with L. donovani either by intradermal needle injection or by infected sand flies, LmCen −/− -immunized hamsters were protected, not showing spleen or liver pathology averting VL fatality compared to control animals. Spleen cells from LmCen −/− immunized and infected sand fly challenged hamsters produced significantly higher Th1-associated cytokines and chemokines including IFN-γ and TNF-α, and significantly reduced expression of the anti-inflammatory cytokines IL-10 and IL-21, compared to non-immunized challenged animals. We further developed a GLP-grade LmCen −/− which showed equal protection as laboratory-grade LmCen −/− parasites in hamsters. Importantly, GLP-grade LmCen −/− parasites also induced a proinflammatory immune response in the PBMCs isolated from healthy people living in non-endemic and endemic for VL as well as cured VL people living in endemic region. Together, this study demonstrates that the LmCen −/− parasites are safe and efficacious against VL and it is a strong candidate vaccine to be tested in a human clinical trial.
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Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2020.11.18.388553
- https://www.biorxiv.org/content/biorxiv/early/2020/11/20/2020.11.18.388553.full.pdf
- OA Status
- green
- Cited By
- 1
- References
- 51
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3098614651
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W3098614651Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1101/2020.11.18.388553Digital Object Identifier
- Title
-
Preclinical validation of a second generation leishmanization vaccine against vector transmitted fatal visceral leishmaniasisWork title
- Type
-
preprintOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2020Year of publication
- Publication date
-
2020-11-20Full publication date if available
- Authors
-
Subir Karmakar, Nevien Ismail, Fabiano Oliveira, James Oristian, Wen‐Wei Zhang, Swarnendu Kaviraj, Kamaleshwar P. Singh, Abhishek Mondal, Sushmita Das, Krishna Pandey, Parna Bhattacharya, Greta Volpedo, Sreenivas Gannavaram, Monika Satoskar, Sanika Satoskar, Rajiv M. Sastry, Claudio Meneses, Shinjiro Hamano, Pradeep Das, Greg Matlashewski, Sanjay Singh, Shaden Kamhawi, Ranadhir Dey, Jesús G. Valenzuela, Abhay R. Satoskar, Hira L. NakhasiList of authors in order
- Landing page
-
https://doi.org/10.1101/2020.11.18.388553Publisher landing page
- PDF URL
-
https://www.biorxiv.org/content/biorxiv/early/2020/11/20/2020.11.18.388553.full.pdfDirect link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
-
https://www.biorxiv.org/content/biorxiv/early/2020/11/20/2020.11.18.388553.full.pdfDirect OA link when available
- Concepts
-
Visceral leishmaniasis, Immune system, Immunology, Leishmania donovani, Proinflammatory cytokine, Leishmania, Spleen, Leishmaniasis, Chemokine, Medicine, Immunization, Biology, Virology, Inflammation, Parasite hosting, World Wide Web, Computer scienceTop concepts (fields/topics) attached by OpenAlex
- Cited by
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1Total citation count in OpenAlex
- Citations by year (recent)
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2021: 1Per-year citation counts (last 5 years)
- References (count)
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51Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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| corresponding_author_ids | https://openalex.org/A5027775199, https://openalex.org/A5089387183, https://openalex.org/A5064339957, https://openalex.org/A5049600371, https://openalex.org/A5060893561, https://openalex.org/A5023917983, https://openalex.org/A5000479943 |
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