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Next-Generation Leishmanization: Revisiting Molecular Targets for Selecting Genetically Engineered Live-Attenuated Leishmania

Despite decades of research devoted to finding a vaccine against leishmaniasis, we are still lacking a safe and effective vaccine for humans. Given this scenario, the search for a new prophylaxis alternative for controlling leishmaniasis should be a global priority. Inspired by leishmanization—a fir...

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Detalles Bibliográficos
Autores principales: Moreira, Paulo O. L., Nogueira, Paula M., Monte-Neto, Rubens L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10145799/
https://www.ncbi.nlm.nih.gov/pubmed/37110466
http://dx.doi.org/10.3390/microorganisms11041043
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author Moreira, Paulo O. L.
Nogueira, Paula M.
Monte-Neto, Rubens L.
author_facet Moreira, Paulo O. L.
Nogueira, Paula M.
Monte-Neto, Rubens L.
author_sort Moreira, Paulo O. L.
collection PubMed
description Despite decades of research devoted to finding a vaccine against leishmaniasis, we are still lacking a safe and effective vaccine for humans. Given this scenario, the search for a new prophylaxis alternative for controlling leishmaniasis should be a global priority. Inspired by leishmanization—a first generation vaccine strategy where live L. major parasites are inoculated in the skin to protect against reinfection—live-attenuated Leishmania vaccine candidates are promising alternatives due to their robust elicited protective immune response. In addition, they do not cause disease and could provide long-term protection upon challenge with a virulent strain. The discovery of a precise and easy way to perform CRISPR/Cas-based gene editing allowed the selection of safer null mutant live-attenuated Leishmania parasites obtained by gene disruption. Here, we revisited molecular targets associated with the selection of live-attenuated vaccinal strains, discussing their function, their limiting factors and the ideal candidate for the next generation of genetically engineered live-attenuated Leishmania vaccines to control leishmaniasis.
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spelling pubmed-101457992023-04-29 Next-Generation Leishmanization: Revisiting Molecular Targets for Selecting Genetically Engineered Live-Attenuated Leishmania Moreira, Paulo O. L. Nogueira, Paula M. Monte-Neto, Rubens L. Microorganisms Review Despite decades of research devoted to finding a vaccine against leishmaniasis, we are still lacking a safe and effective vaccine for humans. Given this scenario, the search for a new prophylaxis alternative for controlling leishmaniasis should be a global priority. Inspired by leishmanization—a first generation vaccine strategy where live L. major parasites are inoculated in the skin to protect against reinfection—live-attenuated Leishmania vaccine candidates are promising alternatives due to their robust elicited protective immune response. In addition, they do not cause disease and could provide long-term protection upon challenge with a virulent strain. The discovery of a precise and easy way to perform CRISPR/Cas-based gene editing allowed the selection of safer null mutant live-attenuated Leishmania parasites obtained by gene disruption. Here, we revisited molecular targets associated with the selection of live-attenuated vaccinal strains, discussing their function, their limiting factors and the ideal candidate for the next generation of genetically engineered live-attenuated Leishmania vaccines to control leishmaniasis. MDPI 2023-04-16 /pmc/articles/PMC10145799/ /pubmed/37110466 http://dx.doi.org/10.3390/microorganisms11041043 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Moreira, Paulo O. L.
Nogueira, Paula M.
Monte-Neto, Rubens L.
Next-Generation Leishmanization: Revisiting Molecular Targets for Selecting Genetically Engineered Live-Attenuated Leishmania
title Next-Generation Leishmanization: Revisiting Molecular Targets for Selecting Genetically Engineered Live-Attenuated Leishmania
title_full Next-Generation Leishmanization: Revisiting Molecular Targets for Selecting Genetically Engineered Live-Attenuated Leishmania
title_fullStr Next-Generation Leishmanization: Revisiting Molecular Targets for Selecting Genetically Engineered Live-Attenuated Leishmania
title_full_unstemmed Next-Generation Leishmanization: Revisiting Molecular Targets for Selecting Genetically Engineered Live-Attenuated Leishmania
title_short Next-Generation Leishmanization: Revisiting Molecular Targets for Selecting Genetically Engineered Live-Attenuated Leishmania
title_sort next-generation leishmanization: revisiting molecular targets for selecting genetically engineered live-attenuated leishmania
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10145799/
https://www.ncbi.nlm.nih.gov/pubmed/37110466
http://dx.doi.org/10.3390/microorganisms11041043
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