The project #2 constitutes one of the three scientific research proposals of this TMRC that focus on zoonotic cutaneous 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 the immunological mechanisms operating for resistance against the parasite as a prerequisite to the development of vaccine against this disease. The specific hypothesis is that both parasite antigens and sand fly saliva molecules could contribute to the induction of immune response and protection. Our main objective is to identify the immune correlates of protection and to compare the immunogenicity of a set of selected proteins of parasite or sand fly origin that might constitute potential candidate vaccines. This will be done using prospective study of L. major infection analyzing the effects of host factors (tested at the baseline of the cohort follow-up) on the resistance against infection, disease occurrence or recurrence.
The specific Aims are: 1- To identify Leishmania-spectf c effective immunological mechanisms operating for resistance against human 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 study will 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 and the intensity of the specific cellular immune response that they induce and its eventual correlation with resistance. 3- To determine if people exposed to phlebotomine sand fly bites develop detectable antibodies and cellular immune response to the vector's saliva, and if so, if there is any association with the clinical expression of Leishmania infection. The antigenicity of a set of ~ 15 saliva antigens of vector origin will be comparatively analyzed.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Specialized Center (P50)
Project #
1P50AI074178-01
Application #
7284543
Study Section
Special Emphasis Panel (ZAI1-GSM-M (J1))
Project Start
2007-10-01
Project End
2012-07-31
Budget Start
2007-08-15
Budget End
2008-07-31
Support Year
1
Fiscal Year
2007
Total Cost
$106,403
Indirect Cost
Name
Institute Pasteur de Tunis
Department
Type
DUNS #
499250553
City
Tunis
State
Country
Tunisia
Zip Code
1002
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Kammoun-Rebai, Wafa; Naouar, Ikbel; Libri, Valentina et al. (2016) Protein biomarkers discriminate Leishmania major-infected and non-infected individuals in areas endemic for cutaneous leishmaniasis. BMC Infect Dis 16:138
Naouar, Ikbel; Boussoffara, Thouraya; Chenik, Mehdi et al. (2016) Prediction of T Cell Epitopes from Leishmania major Potentially Excreted/Secreted Proteins Inducing Granzyme B Production. PLoS One 11:e0147076
Marzouki, Soumaya; Kammoun-Rebai, Wafa; Bettaieb, Jihene et al. (2015) Validation of Recombinant Salivary Protein PpSP32 as a Suitable Marker of Human Exposure to Phlebotomus papatasi, the Vector of Leishmania major in Tunisia. PLoS Negl Trop Dis 9:e0003991
Harrabi, Myriam; Bettaieb, Jihène; Ghawar, Wissem et al. (2015) Spatio-temporal Genetic Structuring of Leishmania major in Tunisia by Microsatellite Analysis. PLoS Negl Trop Dis 9:e0004017
Kharrat, Nadia; Aissa, Imen; Sghaier, Manel et al. (2014) Lipophilization of ascorbic acid: a monolayer study and biological and antileishmanial activities. J Agric Food Chem 62:9118-27
Ghawar, Wissem; Attia, Hanène; Bettaieb, Jihene et al. (2014) Genotype profile of Leishmania major strains isolated from tunisian rodent reservoir hosts revealed by multilocus microsatellite typing. PLoS One 9:e107043
Naouar, Ikbel; Boussoffara, Thouraya; Ben Ahmed, Melika et al. (2014) Involvement of different CD4(+) T cell subsets producing granzyme B in the immune response to Leishmania major antigens. Mediators Inflamm 2014:636039
Bettaieb, Jihene; Toumi, Amine; Chlif, Sadok et al. (2014) Prevalence and determinants of Leishmania major infection in emerging and old foci in Tunisia. Parasit Vectors 7:386
Lemaire, Julien; Mkannez, Ghada; Guerfali, Fatma Z et al. (2013) MicroRNA expression profile in human macrophages in response to Leishmania major infection. PLoS Negl Trop Dis 7:e2478

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