The Utility of a Controlled Human Infection Model for Developing Leishmaniasis Vaccines

Abstract Controlled human infection models (CHIMs) are increasingly recognised as having an important role in the early development of vaccines for important human diseases, including those prevalent in low and middle-income countries. The leishmaniases are a group of clinically disparate parasitic diseases caused by multiple species of Leishmania . Widely heralded as potentially vaccine-preventable, progress in vaccine development for different forms of leishmaniasis has over past decades been slow, hampered by lack of funds, good experimental models and the challenges of progression through the normal clinical trial pathway. However, with a new generation of leishmaniasis vaccine candidates now progressing in clinical development, the value of a robust CHIM able to accelerate early-phase evaluation of new vaccine candidates has become increasingly apparent. Here, we briefly review the historic context of human infection studies in leishmaniasis and outline issues pertinent to the development of a new CHIM of sand fly-transmitted Leishmania major infection. Given the diversity and wide geographic distribution of the leishmaniases, we conclude with a discussion of future needs and challenges in the development of CHIMs for these important neglected diseases.