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

Departments of Pathology and Microbiology, Wexner Medical Center, The Ohio State University, Columbus, OH 43201, USA
Division of Emerging and Transfusion Transmitted Disease, Center for Biologics Evaluation and Research Food and Drug Administration, Silver Spring, MD 20993, USA
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Kwang Poo Chang
Pathogens 2022, 11(4), 431;
Received: 7 March 2022 / Revised: 29 March 2022 / Accepted: 30 March 2022 / Published: 2 April 2022
(This article belongs to the Special Issue Frontiers in Leishmania)
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. View Full-Text
Keywords: Leishmania; visceral leishmaniasis; vaccine; live attenuated parasite vaccines; pan-Leishmania vaccine Leishmania; visceral leishmaniasis; vaccine; live attenuated parasite vaccines; pan-Leishmania vaccine
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MDPI and ACS Style

Volpedo, G.; Bhattacharya, P.; Gannavaram, S.; Pacheco-Fernandez, T.; Oljuskin, T.; Dey, R.; Satoskar, A.R.; Nakhasi, H.L. The History of Live Attenuated Centrin Gene-Deleted Leishmania Vaccine Candidates. Pathogens 2022, 11, 431.

AMA Style

Volpedo G, Bhattacharya P, Gannavaram S, Pacheco-Fernandez T, Oljuskin T, Dey R, Satoskar AR, Nakhasi HL. The History of Live Attenuated Centrin Gene-Deleted Leishmania Vaccine Candidates. Pathogens. 2022; 11(4):431.

Chicago/Turabian Style

Volpedo, Greta, Parna Bhattacharya, Sreenivas Gannavaram, Thalia Pacheco-Fernandez, Timur Oljuskin, Ranadhir Dey, Abhay R. Satoskar, and Hira L. Nakhasi. 2022. "The History of Live Attenuated Centrin Gene-Deleted Leishmania Vaccine Candidates" Pathogens 11, no. 4: 431.

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