The project #2 constitutes one of the three scientific research proposals of this TMRC that focus on zoonoticcutaneous leishmaniasis (ZCL) due to Leishmania (L.) major. The disease is highly prevalent in North Africa,the Middle East and Central Asia. The long-term goal of this proposal (Project #2) is to elucidate theimmunological mechanisms operating for resistance against the parasite as a prerequisite to thedevelopment of vaccine against this disease. The specific hypothesis is that both parasite antigens and sandfly saliva molecules could contribute to the induction of immune response and protection. Our main objectiveis to identify the immune correlates of protection and to compare the immunogenicity of a set of selectedproteins of parasite or sand fly origin that might constitute potential candidate vaccines. This will be doneusing prospective study of L. major infection analyzing the effects of host factors (tested at the baseline ofthe cohort follow-up) on the resistance against infection, disease occurrence or recurrence.
The specificAims are:1- To identify Leishmania-spectfc effective immunological mechanisms operating for resistance againsthuman L. major infection. This will be done by the analysis of indicators of innate or adaptive (memory)cellular response against the parasite and their eventual correlation with resistance against ZCL. The studywill comprise a cohort of exposed individuals living in endemic area of L. mayortransmission (see Project#1).2- To compare the antigenicity of a set of selected proteins of parasite origin by analysing the type andthe intensity of the specific cellular immune response that they induce and its eventual correlation withresistance.3- To determine if people exposed to phlebotomine sand fly bites develop detectable antibodies andcellular immune response to the vector's saliva, and if so, if there is any association with the clinicalexpression of Leishmania infection. The antigenicity of a set of ~ 15 saliva antigens of vector origin will becomparatively analyzed.
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