ABOUT US

Kick-Off

The PREV_PKDL project brings together a multidisciplinary consortium whose partners have complementary expertise in vaccine Research and Development (R&D) - from antigen discovery, over preclinical R&D and up to the early and mid-stage clinical testing of vaccine candidates in clinical trials - management, communication and innovation.

The coordination of the PREV_PKDL project is assured by the Coordinator (Dr Odile Leroy, European Vaccine Initiative (EVI)) assisted by the Management Team (EVI) and the project Steering Committee (SC). To increase the chance of success towards the set objectives, i.e. the development of a safe and effective vaccine to prevent PKDL, the consortium is supported by a Scientific and Ethics Advisory Committee (SEAC) that will provide strategic inputs into scientific-technical, public health and ethical issues.

PREV_PKDL is organised in seven complementary Work Packages, each led by a Work Package Leader.

WP Structure

Background

The leishmaniases are still some of the world’s most neglected diseases, affecting largely the poorest of the poor, mainly in developing countries, and present a severe barrier to socio-economic development.

According to the most recent reports, the leishmaniases affect people in nearly 98 developing and developed countries where about 350 million people are living in these regions. The disease is reported in approximately 12 million people worldwide with recorded incidence of 1.5-2 million new cases each year of cutaneous form and 500,000 new cases of the visceral form of the disease. Collectively, approximately 2.4M disability-adjusted life years (DALY) are lost to the leishmaniases.

1 Kaye, P and Scott, P, Nature Reviews Microbiology 2011. 9:604-615
2 Zijlstra E.E. et al., Post-kala-azar dermal leishmaniasis in the Sudan: clinical presentation and differential diagnosis. Trans R Soc Trop Med Hyg. 2001 Apr;95 Suppl 1:S59-76.

Map Leishmania

Geographical distribution of new visceral leishmaniasis (VL) cases in 2016.
Source: WHO weekly epidemiological record, No 40, 05 October 2018. http://www.who.int/wer/2018/wer9340/en/

There is no licensed vaccine against any form of human leishmaniasis. As recovery from infection is usually accompanied by strong immunity and as it is possible to protect experimental animals using live challenge or with subunit vaccines, hope for developing a vaccine for humans has been strong. Leishmania vaccine development has proven to be a difficult and challenging task, which is mostly hampered by inadequate knowledge of disease pathogenesis and the complexity of immune responses needed for protection. So far, preventative measures are restricted to vector control with insecticides-treated bed nets and indoor residual spray.

Post kala azar dermal leishmaniasis

Post kala azar dermal leishmaniasis (PKDL) is a skin disease which usually develops after treatment for visceral leishmaniasis. PKDL significantly affects quality of life, is often mistaken for leprosy, and can result in stigmatisation that has lifetime impact. In addition to its impact on patients, PKDL patients are also believed to be source of Leishmania infections that lead to outbreaks and epidemics of VL. PKDL is an immunological disease involving a dysregulation of innate and /or acquired immunity that allows parasite persistence in the skin and sustained inflammation3,4. PKDL is a disease of humans and no pre-clinical animal models are available for either detailed mechanistic studies of pathogenesis or for pre-clinical validation of vaccine candidates. Current treatments may cause serious side effects and/or only work well in some settings. Thus, prevention of PKDL represents the most clinically beneficial solution. A novel adenoviral-based vaccine (ChAd63-KH) that can stimulate immune responses that are known to be defective in PKDL patients has been developed and evaluated in a first in human trial5. During the course of this project, the ChAd63-KH vaccine will further be evaluated in two clinical trials in Sudan.

3 Mukhopadhyay D. et al. Trends in parasitology 2014. 30(2):65-74.
4 Ganguly S. et al., International journal of dermatology 2010. 49(8):921-31
5 Osman M. et. al, PLoS neglected tropical diseases, 2017. 11(5):e0005527.

Strategy

Strategy

Work Packages

The main objective of this work package is to set up an effective management framework to ensure that PREV_PKDL progresses towards its planned objectives in line with contractual commitments. The specific objectives are to:

  • Establish an efficient management infrastructure including management bodies, independent scientific advisory and ethics committee and management procedures and tools
  • Conduct the financial and contractual management of the consortium
  • Implement day-to-day operational PREV_PKDL management
  • Ensure observance of the required ethical standards

The main objective of this work package is to conduct a phase IIa clinical trial (LEISH3a) to evaluate the safety of vaccination with ChAd63-KH in Sudanese VL patients previously treated with Sodium Stibogluconate and Paramomycin (SSG/PM). The sponsor of the clinical trial is the University of York. The study will be conducted as an open label study in ~24 patients at the Professor El Hasssan Centre for Tropical Medicine, Doka. LEISH3a will be prospectively registered on ISRCTN and clinicaltrials.gov. The clinical batch that will be used in this trial was previously manufactured with funds from the Wellcome Trust (https://wellcome.ac.uk/what-we-do/teams/innovations-team) and will be kindly donated to this project.

The main objective of this work package are:

  • Manufacture a new clinical lot of ChAd63-KH
  • Conduct bridging immunogenicity studies in rodents
  • Prepare documentation to support use of new clinical lot in subsequent human clinical trials (including LEISH3b)

The main objective of this work package is to conduct a randomised, double blind placebo controlled trial (LEISH3b) to determine whether post treatment vaccination of VL Sudanese patients with ChAd63-KH protects against subsequent development of PKDL. Progression to LEISH3b will be based primarily on safety and preliminary immunogenicity data derived from LEISH3a (WP2). University of York acts as the sponsor of the trial. LEISH3b will be prospectively registered on ISRCTN and clinicaltrials.gov.

The main objective of this work package is to conduct research studies in patients treated for VL from different endemic countries (Sudan, Ethiopia, Kenya and Uganda) to better understand the pathogenesis of the disease and the underlying immune mechanisms. The results of these studies, and the development of research capacity for monitoring immune responses, will help to underpin future research and product evaluation.

The main objective of this work package is to strengthen immunology research capacity in the LEAP countries by promoting the development of a flow cytometry network across the sites. Flow cytometry is indeed a powerful tool for interrogating immune response status, indispensable for quantifying immune responses and monitoring changes in immune status. Particularly for multicentre studies, flow cytometry brings challenges, including access to expertise, equipment support, protocol harmonisation and data management. We will therefore build a network for training and sustainable development of flow cytometry capacity in the east African region. This has both direct value for the trials described here and legacy value that will underpin future vaccine (and drug) trials for leishmaniasis and other diseases affecting these regions.

PREV_PKDL will be a vehicle to promote North-South and South-South collaboration, providing opportunities for EU early career researchers to engage with researchers in Africa. 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.

LEAP

The main objectives of this work package are to:

  • Ensure appropriate, effective communication, and dissemination of project information and results
  • Foster and support exploitation of results and knowledge generated.

The main activities aiming at maximising the long-term impact of PREV_PKDL will ensure that:

  • A comprehensive plan for communication and dissemination is elaborated at the beginning of the project
  • Dissemination and exploitation activities follow a clear strategy and be closely monitored
  • Scientific outcomes is widely disseminated
  • Project results are published in high quality peer-reviewed journals providing open access as early as possible
  • Intellectual property is identified and appropriately protected
  • Exploitation potential and interests are clearly documented
  • High visibility of the project is created among relevant target groups through a set of dedicated communication activities.

Steering Committee

The PREV_PKDL project Steering Committee (SC) is responsible for the scientific and technical coordination of the project and is the ultimate decision-making body of consortium. The SC is composed of the Coordinator (EVI), as well as of one representative of each partner.

The SC is responsible for:

SC Members

Dr Odile Leroy

Dr Odile Leroy (European Vaccine Initiative, Germany)

Trained as a physician, specialised in epidemiology, clinical pharmacology and vaccinology, Dr Odile Leroy has spent most of her carrier in vaccine development, as a scientist in Africa for nine years, as corporate clinical director of airborne vaccines for 10 years at Sanofi Pasteur. She joined EMVI in 2002 as a clinical and regulatory director, and from 2005 to 2006 she lead as executive director of the EDCTP. Since 2009 she is executive director at EVI.

Her main interest is the implementation of best practices in the field of vaccine development against diseases of poverty. In order to maximise concerted European investments, she is coordinating several European vaccine research projects which aim to harmonise and set up rationale decision making criteria. She is also coordinator of the vaccine infrastructure project TRANSVAC. She is member of the Scientific Organising Committee of the Global Immunisation and Vaccine Research Forum co-organised by WHO, NIH, and BMGF.

Prof Paul Kaye

Paul Kaye is Professor of Immunology at the University of York

He trained in zoology (BSc) and immunology (PhD) and has worked for over 30 years on the immunology and immunopathology of the neglected tropical disease leishmaniasis. He is internationally recognized for his research on macrophages and dendritic cells, contributing to a fundamental understanding of their biology in health and disease, and for his work on lymphoid tissue remodelling and granulomatous inflammation during chronic infection. Paul is a Wellcome Trust Senior Investigator and an elected Fellow of the UK Academy of Medical Sciences. He was awarded FRCPath by publication in 2004 and has published ~150 research articles and reviews, with many in leading international journals (e.g. Nature Medicine, Immunity, J. Clin. Invest., PNAS). Paul’s research tackles leishmaniasis from a holistic viewpoint, rooted in the immunology of the host-parasite interaction, but employing tools and approaches taken from many disciplines, including mathematics, ecology, vector biology and neuroscience. He has extensive links with leishmaniasis-endemic countries and is currently leading on Phase II therapeutic vaccine trials in Sudan, developing a digital pathology platform with colleagues in Brazil, India and Sri Lanka and establishing a controlled human infection model for cutaneous leishmaniasis.

Prof Joseph Olobo

Prof Joseph Olobo (Makerere University, Uganda)

Joseph Olobo is a veterinarian by basic training and is professor of Immunology, College of Health Sciences, Makerere University, Kampala, Uganda. He has studied the immunology of diseases including leishmaniasis, trypanosomiasis and tuberculosis. He established the non-human primate model for visceral leishmaniasis for drug and vaccine development. Together with other members of the Leishmaniasis East Africa Platform (LEAP), he is involved in clinical trials for anti-leishmania drug development. Initial trials by LEAP showed that a 17-day combination treatment with SSG/PM was as effective as the 30-day standard SSG. In 2010, the WHO recommended SSG/PM combination as the new first-line treatment for VL patients in eastern Africa. Partly through his efforts, the Department of Immunology and Molecular Biology was recently establishment at the College of Health Sciences, Makerere University.

Dr Margaret Mbuchi

Dr Margaret Mbuchi (Kenya Medical Research Institute, Kenya)

Margaret Mbuchi is a Principal Research Officer at the Kenya Medical Research Institute (KEMRI). She has worked on host-parasite interaction, immunopathogenesis and diagnosis in human visceral leishmaniasis. Margaret has worked extensively in development and field evaluation of simplified molecular and point-of-care diagnostic tests for visceral leishmaniasis in Kenya in collaboration with EU (TRYLEIDIAG Project 2006-2009), World Health Organization 2011 (http://www.who.int/tdr/publications/documents/vl-rdt-evaluation.pdf) and Foundation for Innovative New Diagnostics (2014-2018). She has also worked in collaboration with University of Texas Medical Branch to investigate the role of Signal Transducer and Activator of Transcription-6 (STAT6) in human visceral leishmaniasis in Kenya (2014-2018). Current research interests include characterization of host immune response pathways aimed at identifying potential targets for drug and vaccine development against visceral leishmaniasis. Margaret also teaches at the KEMRI-Institute of Tropical Medicine and Infectious Diseases (ITROMID) graduate school where she is in charge of the Cellular & Molecular Immunology Unit.

Prof Asrat Hailu

Prof Asrat Hailu (University of Gondar, Ethiopia)

Asrat Hailu is a Professor of Immunoparasitology in the College of Health Sciences, School of Medicine, Addis Ababa University, Ethiopia. He has worked at various academic positions at Addis Ababa as Director of Research, and Head of Department. He supervises PhD students and coordinates a post graduate program in Medical Parasitology.

Prof. Asrat has a vast experience on clinical trials evaluating new treatments, diagnostics and vaccines. He has collaborated with DNDi to establish regional centres of excellence for clinical trials focusing on leishmaniasis. He is a member of various professional societies and global networks. His research focuses on parasitic diseases, especially NTDs and malaria; he publishes extensively in scientific journals. He is currently heading a research division of CDT-AFRICA (a World Bank Centre of excellence for Innovative Drug Development and Therapeutic Trials for Africa, based in Ethiopia) as well being the Chair of the Health Working Group at the Ethiopian Academy of Sciences.

Scientific and Ethics Advisory Committee

The Scientific and Ethics Advisory Committee (SEAC) is composed of renowned and independent scientists from the vaccine R&D field, including experts in the fields of ethics and representatives from public organisations and industry.

The SEAC, as a non-executive body, will provide expert scientific and technical advice and recommendations to the consortium, advice on ethical issues raised by the clinical trials and research studies planned by the partners, ensure the efficient exploitation of project results and compliance with the highest ethical standards.

SEAC Members

Prof. Simon Croft

Simon L. Croft BSc PGCE PhD FRSB

Simon Croft is Professor of Parasitology in the Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine (LSHTM). He has worked on the discovery and development of anti-infective drugs in academia, industry and public-private partnerships. Simon’s research has focussed on novel drugs and formulations for the treatment of leishmaniasis, malaria, human African trypanosomiasis and Chagas disease, including projects on miltefosine, AmBisome and topical paromomycin which reached clinical trials for the treatment of leishmaniasis. Current research interests include PK PD relationships, topical formulations, predictive models for drugs and vaccines and leishmaniasis control programmes (KalaCORE and SPEAK India). He works extensively with industry and Product Development Partnership (PDPs) on neglected tropical diseases and a network of collaborators in disease endemic countries. From 2004 to 2007 Simon was the R&D Director of the Drugs for Neglected Diseases Initiative (DNDi), Geneva and from 2008 to 2014 he was Dean of Faculty at the LSHTM.

Giuseppe Del Giudice

Giuseppe Del Giudice, MD, PhD

Dr Giuseppe Del Giudice obtained his M.D. degree and the postgraduated Specialization in Infectious Diseases at the University of Milan, and the PhD degree in Immunology at the University of Geneva, Switzerland.

He spent 12 years in Switzerland studying the immune response to malaria parasites first at the University of Geneva, then at the University of Lausanne, where he got the degree of Professeur Agrégé in Immunology. At the same time he became medical officer (staff member) of the World Health Organization, Division of Communicable Diseases.

In 1996 he returned to Italy as Senior Research Director at the Research Center of Chiron Vaccines, then Novartis Vaccines, now GSK Vaccines in Siena. During these years he covered positions with increasing responsibilities until he became Global Head of Translational Medicine with Novartis Vaccines and now Translational Science Leader with GSK Vaccines. During these years he was responsible of several projects (mainly related to human immunology and translational research) on vaccines against various viral and bacterial diseases as well as on vaccine adjuvants.

Giuseppe Del Giudice is author and co-author of over 270 publications and member of several international societies and scientific institutional and supranational boards.

Prof. Nirmal Kumar Ganguly

Prof. Nirmal Kumar Ganguly

Prof. Nirmal Kumar Ganguly, M.D. is the former Director General, Indian Council of Medical Research (ICMR) and also was formerly a Distinguished Biotechnology Research Professor, Department of Biotechnology, Government of India. Prof. Ganguly has more than 40 years of research and training experience. His major areas of research have been Tropical Diseases, Cardiovascular Diseases and Diarrheal Diseases. His interest encompasses the disciplines of Immunology, Biotechnology and Public Health. Prof. N. K. Ganguly has contributed immensely to Leishmania research and its eradication programmes. As Director General – Indian Council of Medical Research, Prof. Ganguly has initiated several research programmes and clinical trials on new drug combinations for Leishmaniasis. His research has deciphered pathways for mode of infection, immune response and drug efficacy. He has several scientific publications to his credit on Visceral Leishmaniasis. Over the years he has been an active member of several WHO Committees for control, management and eradication of Visceral Leishmaniais.

Prof. David Smith

Prof. David Smith, B.Phil., B.D., S.T.L., M.A., S.T.D.

David Smith is Associate Professor of Health Care Ethics in Royal College of Surgeons in Ireland (RCSI) and Director of the MSc in Health Care Ethics and Law. He is a member of the following Research Ethics Committees in Ireland: Chairperson the Human Research Ethics Committee in RCSI; Chairperson of the Animal Research Ethics Committee in RCSI; Member of the Rotunda Research Ethics Committee; Member of the Research Ethics Committee Beaumont University Hospital, Dublin; Member of the Faculty Research Ethics Committee – Faculty of Health Science – Trinity College; Member of the Daughters of Charity Services Research Ethics Committee; Chairperson of the Bon Secours Health System Research Ethics Committee; Members of the Research Ethics Committee of the Faculty of Public Health. He is also ethics consultant to following HP7 and H2020 projects:

  • H2020 PREV_PKDL
  • H2020 PurinexDX
  • H2020 Programme TRANSVAC2
  • H2020 Gliotrain
  • H2020 Watersproutt
  • H2020 Programme ZIKAVAX
  • H2020 Programme SURG-Africa
  • H2020 Programme DRIVE
  • H2020 COST Action IS1303
  • FP7-funded programme EPIMIRNA
  • FP7 entitled Hypotension in Prems HIP

Before the official start of their mandate, all SEAC members have signed a non-disclosure agreement, a declaration of conflict of interest and a declaration of commitment to the project.