Safety and reactogenicity of a controlled human infection model of sand fly-transmitted cutaneous leishmaniasis
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F24%3A10494214" target="_blank" >RIV/00216208:11310/24:10494214 - isvavai.cz</a>
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=ZEkwksCIzK" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=ZEkwksCIzK</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41591-024-03146-9" target="_blank" >10.1038/s41591-024-03146-9</a>
Alternative languages
Result language
angličtina
Original language name
Safety and reactogenicity of a controlled human infection model of sand fly-transmitted cutaneous leishmaniasis
Original language description
The leishmaniases are globally important parasitic diseases for which no human vaccines are currently available. To facilitate vaccine development, we conducted an open-label observational study to establish a controlled human infection model (CHIM) of sand fly-transmitted cutaneous leishmaniasis (CL) caused by Leishmania major. Between 24 January and 12 August 2022, we exposed 14 participants to L. major-infected Phlebotomus duboscqi. The primary objective was to demonstrate effectiveness of lesion development (take rate) and safety (absence of CL lesion at 12 months). Secondary and exploratory objectives included rate of lesion development, parasite load and analysis of local immune responses by immunohistology and spatial transcriptomics. Lesion development was terminated by therapeutic biopsy (between days 14 and 42 after bite) in ten participants with clinically compatible lesions, one of which was not confirmed by parasite detection. We estimated an overall take rate for CL development of 64% (9/14). Two of ten participants had one and one of ten participants had two lesion recurrences 4-8 months after biopsy that were treated successfully with cryotherapy. No severe or serious adverse events were recorded, but as expected, scarring due to a combination of CL and the biopsy procedure was evident. All participants were lesion free at >12-month follow-up. We provide the first comprehensive map of immune cell distribution and cytokine/chemokine expression in human CL lesions, revealing discrete immune niches. This CHIM offers opportunities for vaccine candidate selection based on human efficacy data and for a greater understanding of immune-mediated pathology.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10600 - Biological sciences
Result continuities
Project
<a href="/en/project/EF16_019%2F0000759" target="_blank" >EF16_019/0000759: Centre for research of pathogenicity and virulence of parasites</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Nature Medicine
ISSN
1078-8956
e-ISSN
1546-170X
Volume of the periodical
30
Issue of the periodical within the volume
11
Country of publishing house
US - UNITED STATES
Number of pages
13
Pages from-to
3150-3162
UT code for WoS article
001283351200006
EID of the result in the Scopus database
2-s2.0-85200241603