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• European Commission
• Research
• Health
• Infectious Diseases
• FP7 projects

PRe-clinicAl studies of a PSA-based human vaccine candidate targeting visceral, cutaneOus and mucocutaneous Leishmaniasis and Development of the associated procedures for further clinIcal trials

Summary:

The global aim of RAPSODI is :

• to develop a human vaccine candidate against most or all Leishmania species that cause the most severe leishmaniasis in the world. An unique vaccinal solution will thus be provided to protect against the various clinical phenotypes (namely visceral, cutaneous and mucocutaneaous leishmaniasis, VL, CL and ML respectively).
• to establish all the associated procedures required for the subsequent clinical trials, such as the selection of the appropriate patients and assessment of vaccine efficiency.

Based on successful results on VL dogs, the best VL animal model to date, RAPSODI will propose a second generation human-compatible vaccine candidate and confirm its activity in pre-clinical studies. As the chosen antigen is common to most, if not all, Leishmania species, an ambitious universal immunoprotective response is being sought. RAPSODI will also address the question of population selection in order to ascertain relevant and meaningful clinical trials and vaccination campaigns. Indeed, resistant individuals, when involved in either vaccinated or placebo groups, represent important bias to the analysis of the results. RAPSODI will investigate further the parasitological, immunological and genetic features of such clinical status, and will subsequently apply the generated knowledge to the development of assays and field tests, which represent stand-alone results.

Problem:

Leishmaniasis paradox is to be considered as a neglected disease and to be the second most-dreaded parasitic disease in the modern world. Leishmaniases are widespread in 88 endemic countries on all continents except Antarctica, with 350 million people at risk, 14 million human cases permanently affected and an estimated annual incidence of 2 million cases. This results in a global morbidity of 2,090 thousands DALYs (Disability Adjusted Life Years) and a mortality rate of 59,000/year (WHO report A60/10, 2007). A prophylactic vaccine would greatly enhance the situation. In endemic areas, most of the infected people do not develop clinical symptoms and past episode of leishmaniasis leads to lifelong immunity against re-infection with the same subspecies, once the infection is healed. This makes the development of such a vaccine a realistic goal. But, in order to provide efficient vaccination campaigns, one should be able to :

• distinguish naturally infected but asymptomatic people from non infected ones,
• determine whether an exposed uninfected or infected but asymptomatic individual will remain asymptomatic (natural and/or acquired resistance to leishmaniasis) or will develop symptomatic disease (susceptibility).

Aim:

The main goal of the project is to develop a human vaccine candidate targeting most, if not all, Leishmania species that cause the different clinical manifestations of Leishmaniasis and all the associated procedures and methods required for the subsequent clinical trials, i.e. selection of the appropriate population, assessment and follow-up of vaccine efficacy and evaluation of the impact of future human vaccination trials on disease’s prevalence.

Results:

RAPSODI should lead to the following outputs :

• A human synthetic vaccine candidate;
• Predictive immunoassays (1 qualitative and 1 quantitative) for identification of susceptible individuals (unable to control parasite dissemination and developing severe and progressive Leishmaniasis) and vaccinated subjects (to be distinguished from infected ones);
• A marker signature for genetic susceptibility assessment;
• An immunoassay for vaccination follow-up. All these products are intended to enable the forthcoming clinical trials and the steps beyond.

Potential applications:

RAPSODI is targeting the human forms of leishmaniasis, but some of the results should be of benefit to the veterinarian community, as leishmaniasis is also affecting dogs. As dogs are reservoirs for Leishmania, providing protective solution to animals should help controlling the infection of human beings.

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