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Safety and reactogenicity of a controlled human infection model of sand fly-transmitted cutaneous leishmaniasis

V. Parkash, H. Ashwin, S. Dey, J. Sadlova, B. Vojtkova, K. Van Bocxlaer, R. Wiggins, D. Thompson, NS. Dey, CL. Jaffe, E. Schwartz, P. Volf, CJN. Lacey, AM. Layton, PM. Kaye

. 2024 ; 30 (11) : 3150-3162. [pub] 20240802

Language English Country United States

Document type Journal Article, Observational Study

Persistent link   https://www.medvik.cz/link/bmc25003709

Grant support
MR/R014973 RCUK | Medical Research Council (MRC)
CePaViP 16_019/0000759 EC | European Regional Development Fund (Europski Fond za Regionalni Razvoj)

E-resources Online Full text

NLK ProQuest Central from 2000-01-01 to 1 year ago
Health & Medicine (ProQuest) from 2000-01-01 to 1 year ago

Links

PubMed 39095597
DOI 10.1038/s41591-024-03146-9
Knihovny.cz E-resources

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 .

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