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The History of Live Attenuated Centrin Gene-Deleted Leishmania Vaccine Candidates

Leishmaniasis, caused by an infection of the Leishmania protozoa, is a neglected tropical disease and a major health problem in tropical and subtropical regions of the world, with approximately 350 million people worldwide at risk and 2 million new cases occurring annually. Current treatments for le...

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Autores principales: Volpedo, Greta, Bhattacharya, Parna, Gannavaram, Sreenivas, Pacheco-Fernandez, Thalia, Oljuskin, Timur, Dey, Ranadhir, Satoskar, Abhay R., Nakhasi, Hira L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9025045/
https://www.ncbi.nlm.nih.gov/pubmed/35456106
http://dx.doi.org/10.3390/pathogens11040431
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author Volpedo, Greta
Bhattacharya, Parna
Gannavaram, Sreenivas
Pacheco-Fernandez, Thalia
Oljuskin, Timur
Dey, Ranadhir
Satoskar, Abhay R.
Nakhasi, Hira L.
author_facet Volpedo, Greta
Bhattacharya, Parna
Gannavaram, Sreenivas
Pacheco-Fernandez, Thalia
Oljuskin, Timur
Dey, Ranadhir
Satoskar, Abhay R.
Nakhasi, Hira L.
author_sort Volpedo, Greta
collection PubMed
description Leishmaniasis, caused by an infection of the Leishmania protozoa, is a neglected tropical disease and a major health problem in tropical and subtropical regions of the world, with approximately 350 million people worldwide at risk and 2 million new cases occurring annually. Current treatments for leishmaniasis are not highly efficacious and are associated with high costs, especially in low- and middle-income endemic countries, and high toxicity. Due to a surge in the incidence of leishmaniases worldwide, the development of new strategies such as a prophylactic vaccine has become a high priority. However, the ability of Leishmania to undermine immune recognition has limited our efforts to design safe and efficacious vaccines against leishmaniasis. Numerous antileishmanial vaccine preparations based on DNA, subunit, and heat-killed parasites with or without adjuvants have been tried in several animal models but very few have progressed beyond the experimental stage. However, it is known that people who recover from Leishmania infection can be protected lifelong against future infection, suggesting that a successful vaccine requires a controlled infection to develop immunologic memory and subsequent long-term immunity. Live attenuated Leishmania parasites that are non-pathogenic and provide a complete range of antigens similarly to their wild-type counterparts could evoke such memory and, thus, would be effective vaccine candidates. Our laboratory has developed several live attenuated Leishmania vaccines by targeted centrin gene disruptions either by homologous recombination or, more recently, by using genome editing technologies involving CRISPR-Cas9. In this review, we focused on the sequential history of centrin gene-deleted Leishmania vaccine development, along with the characterization of its safety and efficacy. Further, we discussed other major considerations regarding the transition of dermotropic live attenuated centrin gene-deleted parasites from the laboratory to human clinical trials.
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spelling pubmed-90250452022-04-23 The History of Live Attenuated Centrin Gene-Deleted Leishmania Vaccine Candidates Volpedo, Greta Bhattacharya, Parna Gannavaram, Sreenivas Pacheco-Fernandez, Thalia Oljuskin, Timur Dey, Ranadhir Satoskar, Abhay R. Nakhasi, Hira L. Pathogens Review Leishmaniasis, caused by an infection of the Leishmania protozoa, is a neglected tropical disease and a major health problem in tropical and subtropical regions of the world, with approximately 350 million people worldwide at risk and 2 million new cases occurring annually. Current treatments for leishmaniasis are not highly efficacious and are associated with high costs, especially in low- and middle-income endemic countries, and high toxicity. Due to a surge in the incidence of leishmaniases worldwide, the development of new strategies such as a prophylactic vaccine has become a high priority. However, the ability of Leishmania to undermine immune recognition has limited our efforts to design safe and efficacious vaccines against leishmaniasis. Numerous antileishmanial vaccine preparations based on DNA, subunit, and heat-killed parasites with or without adjuvants have been tried in several animal models but very few have progressed beyond the experimental stage. However, it is known that people who recover from Leishmania infection can be protected lifelong against future infection, suggesting that a successful vaccine requires a controlled infection to develop immunologic memory and subsequent long-term immunity. Live attenuated Leishmania parasites that are non-pathogenic and provide a complete range of antigens similarly to their wild-type counterparts could evoke such memory and, thus, would be effective vaccine candidates. Our laboratory has developed several live attenuated Leishmania vaccines by targeted centrin gene disruptions either by homologous recombination or, more recently, by using genome editing technologies involving CRISPR-Cas9. In this review, we focused on the sequential history of centrin gene-deleted Leishmania vaccine development, along with the characterization of its safety and efficacy. Further, we discussed other major considerations regarding the transition of dermotropic live attenuated centrin gene-deleted parasites from the laboratory to human clinical trials. MDPI 2022-04-02 /pmc/articles/PMC9025045/ /pubmed/35456106 http://dx.doi.org/10.3390/pathogens11040431 Text en © 2022 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
Volpedo, Greta
Bhattacharya, Parna
Gannavaram, Sreenivas
Pacheco-Fernandez, Thalia
Oljuskin, Timur
Dey, Ranadhir
Satoskar, Abhay R.
Nakhasi, Hira L.
The History of Live Attenuated Centrin Gene-Deleted Leishmania Vaccine Candidates
title The History of Live Attenuated Centrin Gene-Deleted Leishmania Vaccine Candidates
title_full The History of Live Attenuated Centrin Gene-Deleted Leishmania Vaccine Candidates
title_fullStr The History of Live Attenuated Centrin Gene-Deleted Leishmania Vaccine Candidates
title_full_unstemmed The History of Live Attenuated Centrin Gene-Deleted Leishmania Vaccine Candidates
title_short The History of Live Attenuated Centrin Gene-Deleted Leishmania Vaccine Candidates
title_sort history of live attenuated centrin gene-deleted leishmania vaccine candidates
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9025045/
https://www.ncbi.nlm.nih.gov/pubmed/35456106
http://dx.doi.org/10.3390/pathogens11040431
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