This project is part of the EDCTP2 Programme supported by the European Union (RIA2016V-1640)
A B O U T US
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 Flavia D'Alessio, 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.
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.
Caused by more than 20 species of the protozoan parasite Leishmania. These parasites are transmitted to humans by the bites of the infected female phlebotomine sand flies.
There are three main forms of leishmaniasis:
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Cutaneous leishmaniasis (CL);
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Visceral leishmaniasis (VL, also known as kala-azar);
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Mucocutaneous leishmaniasis (MCL).
Whereas cutaneous and mucocutaneous leishmaniasis are chronic and non-life-threatening, visceral leishmaniasis is responsible for over 20,000 deaths per year, second only to malaria amongst parasites in regard to mortality. The organ site and the severity of the disease depends on the Leishmania species, and host immune status (1).
Between 20 to circa 55% (depending on geographical location) of visceral leishmaniasis patients develop a syndrome known as post kala-azar dermal leishmaniasis (PKDL), a severe and chronic form of cutaneous leishmaniasis that usually develops after treatment for VL caused by L. donovani, but which can occur in the absence of previous VL or concomitant with VL therapy (2).
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.
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(1) Kaye, P and Scott, P, Nature Reviews Microbiology 2011. 9:604-615
(2) Zijlstra E.E. et al., Trans R Soc Trop Med Hyg. 2001 Apr;95 Suppl 1:S59-76.
90% of VL cases reported occur in seven countries:
Brazil, Ethiopia, Kenya, India, Somalia, South Sudan and Sudan
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 inflammation (3,4). 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 trial (5). During the course of this project, the ChAd63-KH vaccine will further be evaluated in healthy Sudanese volunteers aged 12-17 years in a safety, immunogenicity and efficacy phase Ib/II clinical trial.
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(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
PREV_PKDL aims to evaluate ChAd63-KH as a vaccine for prevention of visceral leishmaniasis (VL) and post kala azar dermal leishmaniasis (PKDL)
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WORK PACKAGES
PREV_PKDL is organised in seven complementary Work Packages (WP), each led by a Work Package Leader.
WP1
Sustainability, Enhanced collaboration, Research excellence, Impact on policy, Benefits to Regional and Global health
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:
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Monitoring the progress of the overall strategic objectives of the consortium
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Ensuring the effectively implementation of the work programme to achieve the deliverables and milestones
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The financial allocation and distribution of the project resources
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Decision about publications, dissemination, ethical issues, data protection and Intellectual Property rights
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Acceptance of new partners in the consortium
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The appointment of the scientific ethics advisory committee and other committees
Prof. Ahmed Musa
Institute of Endemic Diseases, University of Khartoum, Sudan
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.
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.
Assoc. Prof. Stephen Cose
Head, Immunology Platform & Group Leader, Medical Research Council / Uganda Virus Research Institute & London School of Hygiene and Tropical Medicine Uganda Research Unit, Uganda
