Ex Vivo Immunogenicity Screening of Vaccine Candidate Antigen Combinations in Ethiopian Patients With Leishmaniasis

NCT07783243 | Recruiting DMC

• 1 other identifier: 1950/25
• Study Type: observational
• Target: 90
• Locations: 1 country
• Sites: 2

Brief Summary

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).

Conditions

Immunogenicity; Leishmaniasis, Cutaneous; Leishmaniasis; Leishmaniasis, Visceral

Keywords

leishmania vaccine candidate antigens; leishmania vaccine; leishmaniasis vaccine

Outcome Measures

Primary Outcomes (1)

• 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.

  "Day 0" (baseline) until "Day 17" or "Day 28" (end of treatment, may vary due to treatment)

Secondary Outcomes (5)

• 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

  "Day 0" (baseline) until "Day 17" or "Day 28" (end of treatment, may vary due to treatment)

• To compare the induced T-cell response of IPX-derived Leishmania antigens with GLP-SLA in blood versus tissues, by clinical presentation

  "Day 0" (baseline) until "Day 17" or "Day 28" (end of treatment, may vary due to treatment)

• 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

  "Day 0" (baseline) until "Day 17" or "Day 28" (end of treatment, may vary due to 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

  "Day 0" (baseline), "Day 7", until "Day 17" or "Day 28" (end of treatment, may vary due to treatment)

• To characterize the HLA-TCR interactions involved in the recognition of IPX-derived Leishmania antigens through TCR sequencing and HLA typing

  "Day 0" (baseline) until "Day 17" or "Day 28" (end of treatment, may vary due to treatment)

Study Arms (3)

Ethiopian non-infected healthy volunteers

cutaneous leishmaniasis

visceral leishmaniasis

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Ethiopian population

You may qualify if:

• 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.
• Suspected diagnosis of VL or CL, defined as:
• 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.
• Willing and able to provide informed consent Ensures autonomy and understanding, allowing participants to fully understand their risks and benefits, and the possibility to withdraw at any time without affecting care.

You may not qualify if:

• 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
• Have received immunosuppressive drugs in the past month
• Have received a vaccine in the past month
• Have received modern antileishmanial treatment in the past month
• Are on anticoagulation medication or have bleeding disorders that would contraindicate safe blood or tissue sampling
• For CL patients:
• Primary lesion size \< 2 cm
• Too difficult or too painful sampling zone (e.g., close to the mucosa or lymphatic system, on joints, eyelid or ear)
• Not eligible for systemic SSG treatment
• Ethiopian 'non-infected' healthy volunteers
• Aged 18-65 years Matching the age range of VL and CL patients
• Generally healthy Ensures volunteers who are not in a state of severe medical nor socioeconomic vulnerability, to ensure that participation is not unduly influenced by financial compensation.

Sponsors & Collaborators

• Universiteit Antwerpen: collaborator
• Institute of Tropical Medicine, Belgium: lead

Study Sites (2)

Armauer Hansen Research Institute

Addis Ababa, Ethiopia

RECRUITING

Leishmaniasis Research and Treatment Center

Gonder, Ethiopia

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

PBMCs (VL and CL) lesion biopsies (CL)

MeSH Terms

Conditions

Leishmaniasis, Cutaneous; Leishmaniasis; Leishmaniasis, Visceral

Condition Hierarchy (Ancestors)

Euglenozoa Infections; Protozoan Infections; Parasitic Diseases; Infections; Skin Diseases, Parasitic; Vector Borne Diseases; Skin Diseases, Infectious; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Thao-Thy Pham

  Institute of Tropical Medicine Antwerp

  PRINCIPAL INVESTIGATOR

• Wim Adriaensen, PhD

  Institute of Tropical Medicine Antwerp

  PRINCIPAL INVESTIGATOR

• Eshetu Molla, PhD

  Armauer Hansen Research Institute, Ethiopia

  PRINCIPAL INVESTIGATOR

• Endalamaw Gadisa, PhD

  Armauer Hansen Research Institute, Ethiopia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Eshetu Molla, PhD

CONTACT

00251 9 12 35 62 50; eshetmolla@gmail.com

Thao-Thy Pham, PhD

CONTACT

+32(0)33455227; thaothypham@itg.be

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 90 Days
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 15, 2026
• First Posted: August 24, 2026
• Study Start: May 26, 2026
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: August 24, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF

Locations

ET (2)