Project: Clinical development of a therapeutic vaccine for prevention of post kala azar dermal leishmaniasis

Acronym PREV-PKDL (Reference Number: RIA2016V-1640)
Duration 01/04/2018 - 30/06/2023
Project Topic Post kala azar dermal leishmaniasis (PKDL) is a skin disease that follows treatment for visceral leishmaniasis (VL; kala azar). In addition to its impact on patients, PKDL is widely considered a threat to the elimination of VL. The incidence, clinical presentation and chronicity of PKDL varies geographically. In Sudan nearly a third of cured VL patients develop PKDL within 12 months. Approximately eighty percent of these cases self cure after several months, but drug toxicity (e.g. nephroptoxicity) precludes early treatment. The stigma of PKDL significantly reduces quality of life, particularly for children and women. In contrast, patients with persistent or severe disease receive twenty intravenous injections of AmBisome. Whilst safer / shorter treatment options are desirable, prevention of PKDL represents the most clinically beneficial solution. PKDL is an immunological disease involving a dysregulation of innate and /or acquired imunity that allows parasite persistence in the skin and sustained inflammation. We have recently developed a “third generation” leishmaniasis vaccine (ChAd63-KH) that can stimulate immune responses that are known to be defective in PKDL patients, leading us to hypothesise that inducing these response by vaccination will have therapeutic benefit. We will evaluate ChAd63-KH in two clinical trials in clinically cured VL patients: i) a dose escalation, age de-escalation Phase IIa safety study, and ii) a Phase IIb safety and efficacy study, powered to detect a reduction in PKDL incidence. The results of these trials will be decisive in the future development of ChAd63-KH. To better understand differences in disease natural history as well as drug and vaccine response, we will conduct multidimensional, multiparameter phenotyping (flow cytometry and immunohistochemistry, parasite genomics, clinical scoring) on patient cohorts recruited across the Leishmaniasis East Africa Platform (LEAP; Ethiopia, Kenya, Sudan and Uganda). We will seek to: i) classify sub groups of patients at clinical “cure”, ii) identify biomarkers prognostic of PKDL development and iii) answer fundamental questions related to VL / PKDL pathogenesis. To support the current project and to provide a legacy for future clinical research, clinical trials and disease surveillance activities, we will grow the infrastructure for immunology research, via an integrated flow cytometry network operating across LEAP. This capacity strengthening, including investment in capital and people, will help LEAP to develop as a major force for research and training on poverty-related neglected diseases in the East African Region.
Network EDCTP2
Call Vaccines for poverty-related diseases (PRDs)

Project partner

Number Name Role Country
1 European Vaccine Initiative (EVI) Coordinator Germany
2 University of York Partner United Kingdom
3 University of Khartoum Partner Sudan
4 Makerere University Partner Uganda
5 Kenya Medical Research Institute (KEMRI) Partner Kenya
6 University of Gondar Partner Ethiopia