Safety and reactogenicity of a controlled human infection model of sand fly-transmitted cutaneous leishmaniasis
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, pozorovací studie
Grantová podpora
MR/R014973/1
Medical Research Council - United Kingdom
CePaViP 16_019/0000759
EC | European Regional Development Fund (Europski Fond za Regionalni Razvoj)
MR/R014973
RCUK | Medical Research Council (MRC)
PubMed
39095597
PubMed Central
PMC11564116
DOI
10.1038/s41591-024-03146-9
PII: 10.1038/s41591-024-03146-9
Knihovny.cz E-zdroje
- MeSH
- dospělí MeSH
- Leishmania major * imunologie MeSH
- leishmanióza kožní * imunologie parazitologie patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- parazitární zátěž MeSH
- Phlebotomus parazitologie imunologie MeSH
- zvířata MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
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. ClinicalTrials.gov identifier: NCT04512742 .
Department of Parasitology Faculty of Science Charles University Prague Czech Republic
Skin Research Centre Hull York Medical School York UK
York and Scarborough Teaching Hospitals NHS Foundation Trust York UK
York Biomedical Research Institute Hull York Medical School University of York York UK
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ClinicalTrials.gov
NCT04512742