Characterization of a new<i>Leishmania major</i>isolate for use in a controlled human infection model

Ashwin, Helen; Sádlová, Jovana; Vojtková, Barbora; Bečvář, Tomáš; Lypaczewski, Patrick; Schwartz, Eli; Greensted, Elizabeth; Bocxlaer, Katrien Van; Pasin, Marion; Lipinski, Kai S.; Parkash, Vivak; Matlashewski, Greg; Layton, Alison; Lacey, Charles; Jaffe, Charles L.; Volf, Petr; Kaye, Paul M.

doi:10.1101/2020.08.12.245936

Cited by 2 publications

(1 citation statement)

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“…One approach may be to consider a controlled human infection model (CHIM) that could provide a pathway for accelerated vaccine development and to identify correlates of protection. Recently, L. major strains have been developed under GMP conditions and characterized for potential use in CHIM studies that can be used in CL vaccine trials ( Ashwin et al., 2021 ). CHIM trials would not however be possible for VL due to the risk from challenge infections with a visceral disease causing Leishmania species such as L. donovani.…”

Section: Alternative Methods For Determining the Efficacy Of A L mentioning

confidence: 99%

Revival of Leishmanization and Leishmanin

Pacheco-Fernández

Volpedo

Gannavaram

et al. 2021

Front. Cell. Infect. Microbiol.

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Leishmaniasis includes a spectrum of diseases ranging from debilitating cutaneous to fatal visceral infections. This disease is caused by the parasitic protozoa of the genus Leishmania that is transmitted by infected sandflies. Over 1 billion people are at risk of leishmaniasis with an annual incidence of over 2 million cases throughout tropical and subtropical regions in close to 100 countries. Leishmaniasis is the only human parasitic disease where vaccination has been successful through a procedure known as leishmanization that has been widely used for decades in the Middle East. Leishmanization involved intradermal inoculation of live Leishmania major parasites resulting in a skin lesion that following natural healing provided protective immunity to re-infection. Leishmanization is however no longer practiced due to safety and ethical concerns that the lesions at the site of inoculation that can last for months in some people. New genome editing technologies involving CRISPR has now made it possible to engineer safer attenuated strains of Leishmania, which induce protective immunity making way for a second generation leishmanization that can enter into human trials. A major consideration will be how the test the efficacy of a vaccine in the midst of the visceral leishmaniasis elimination program. One solution will be to use the leishmanin skin test (LST) that was also used for decades to determine exposure and immunity to Leishmania. The LST involves injection of antigen from Leishmania in the skin dermis resulting in a delayed type hypersensitivity (DTH) immune reaction associated with a Th1 immune response and protection against visceral leishmaniasis. Reintroduction of novel approaches for leishmanization and the leishmanin skin test can play a major role in eliminating leishmaniasis.

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Section: Alternative Methods For Determining the Efficacy Of A L mentioning

confidence: 99%

Revival of Leishmanization and Leishmanin

Pacheco-Fernández

Volpedo

Gannavaram

et al. 2021

Front. Cell. Infect. Microbiol.

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Leishmaniases

Chang¹

2021

Encyclopedia of Life Sciences

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Leishmaniases are neglected tropical diseases. The causative agents, Leishmania spp., are transmitted by the blood‐sucking female sand flies. The diseases are largely a zoonosis of canines, rodents and edentates. Humans are accidental dead‐end hosts, except in some places where human–human transmission is indicated by the absence of animal reservoirs. The diseases are present in >100 countries, mainly in tropical and subtropical areas, putting one billion world population at risk with an annual caseload of ∼one million and death in the tens of thousands. Leishmaniases are marked by a spectrum of clinical manifestations, ranging from self‐healing cutaneous lesions to facial mucocutaneous disfiguration to visceralisation with fatal consequence. Clinical managements of visceral leishmaniases rely on several toxic drugs with decreasing efficacy due to the development of drug resistance. Intraphagolysosomal parasitism of macrophages by these parasites is a key feature for considering molecular mechanisms of their virulence relevant to developing effective drugs and vaccines needed. Key Concepts The trypanosomatid protozoa in the genus of Leishmania cause leishmaniases. The diseases are neglected, but very widespread mainly in tropical and subtropical countries. The parasites live briefly in blood‐sucking sand flies and develop into infective promastigotes in the gut lumen. Infected sand flies transmit the parasites among animals, e.g. canines, rodents and edentates. Humans acquire leishmaniases from sand fly bites as a zoonosis with infected wild and domestic animals as the reservoirs. Human leishmaniasis is referred to as anthroponotic where reservoir animals have not been identified. The parasites live in the acidic endosomes/lysosomes of macrophages as amastigotes in the mammalian hosts. There are cutaneous, mucocutaneous and visceral leishmaniases. The spectrum of clinical manifestations results from immunopathology of different host‐parasite interactions. Life‐long immunity to leishmaniases often develops in patients cured of these diseases. Chemotherapy of leishmaniases relies on toxic drugs and loses its effectiveness to drug‐resistance. Visceral leishmaniasis has been brought under control in some endemic countries. Control programs include diagnosis of patients for treatments, surveillance of reservoirs and vectors for elimination. Lack of incentives for drug and vaccine development accounts for the persistence of leishmaniases.

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Characterization of a newLeishmania majorisolate for use in a controlled human infection model

Cited by 2 publications

References 75 publications

Revival of Leishmanization and Leishmanin

Revival of Leishmanization and Leishmanin

Leishmaniases

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