This study assesses the immunoprevalence (presence of the induced T-cell response across different patients (and thus HLA types) of six prioritized IPX-derived Leishmania antigens, using Good Laboratory Practice-grade soluble Leishmania antigen (GLP-SLA) as a positive control. Longitudinal GLP-SLA stimulation validates its IFN-γ release assay performance to support licensing of a QuantiFERON-like test (Leish-IGRA) for treatment monitoring. IPX-derived Leishmania antigen screening focuses on day 0 and EOT, while GLP-SLA includes all timepoints. Induced T-cell responses by ex vivo stimulation of blood and tissue samples (lesion, bone marrow, or spleen) from patients with cutaneous and visceral leishmaniasis (two-centre cohort) before and after treatment will be verified. Samples from Ethiopian 'non-infected' healthy volunteers will be included in parallel to differentiate from Leishmania antigen-specific versus aspecific T-cell activation. The induced T-cell response will mainly be determined by the expressed IFN-γ levels after stimulation. Additional analyses are included to further characterize the activation and cytokine profiles of these IPX-derived Leishmania antigen-specific T-cells, while the breadth of the T-cell response will be determined by mapping the response across different patients (and thus different HLA types).
VL and CL patients
Aged 18-65 years To minimize variability within this first study to verify induced T-cell responses specifically towards vaccine candidate target antigens/peptide pools, we focus on more robust adult immune responses. Children and elderly are vulnerable populations with divergent immune responses and are therefore excluded.
VL: Clinically suspected VL presentation (e.g., prolonged fever, splenomegaly)
CL: Clinically suspected lesions (e.g., nodular, ulcerative, or plaque-like lesions) Including suspected VL and CL patients was done in earlier VL and CL studies (Clinicaltrials.gov Identifier: NCT05602610 and NCT05332093, >95% of suspected cohort confirmed to have VL or CL, respectively) to facilitate efficient recruitment flow for both the patient as the study team.
Are currently enrolled in another interventional clinical study
Have known severe comorbidities (e.g., autoimmune disease, HIV, tuberculosis, leprosy, or malaria)
Have known pregnancy
Cognitively impaired individuals
Ethiopian population
Cohort
Prospective
Not listed
To determine the immunoprevalence of IPX-derived Leishmania antigens and their combinations in Ethiopian patients with VL and CL.
Proportion of patients that demonstrate an induced T-cell response (represented by IFN-γ expression) after ex vivo stimulation of IPX-derived antigens Leishmania and combinations.
To further characterize the phenotype (e.g., flow cytometry, single-cell sequencing) and polyfunctionality (multiplex cytokine determination) of the induced T-cell response after ex vivo stimulation with IPX-derived Leishmania antigens and GLP-SLA
To compare the induced T-cell response of IPX-derived Leishmania antigens with GLP-SLA in blood versus tissues, by clinical presentation
To determine the dynamics of the induced T-cell response of IPX-derived Leishmania antigens versus GLP-SLA before and at end of successful versus failed treatment
To assess the predictive value of the Leish-IGRA for treatment outcome in CL and VL patients before, during and at end of treatment
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Institute of Tropical Medicine, Belgium
Lead sponsor
Universiteit Antwerpen
Collaborator