Projet de thèse en Biologie Santé
Sous la direction de Jean-loup Lemesre.
Thèses en préparation à Montpellier , dans le cadre de Sciences Chimiques et Biologiques pour la Santé , en partenariat avec INTERTRYP-Interactions hôte - vecteur - parasite - environnement -dans les maladies tropicales négligées dues aux Trypanosomatidés. (laboratoire) depuis le 03-11-2015 .
Development of a multi-epitope peptide vaccine against human leishmaniasis.
Leishmaniasis is a vector-borne neglected tropical disease endemic to 98 countries, including in Europe. Twenty Leishmania species are capable of establishing intracellular infection within human macrophages, causing different clinical presentations - cutaneous, mucocutaneous and visceral leishmaniasis. Natural protection against infection is characterized by a dominant Th1 cellular immune response, with production of IFN-γ, IL-2 and TNF-α by polyfunctional CD4+ T cells, ultimately leading to macrophage activation and parasite killing, whereas Th2 responses are associated with disease progression. To date, there is no effective human vaccine, one of the top public health priorities to control and eliminate leishmaniases. We aim to develop an epitope-based vaccine, a promising approach to achieve protective immunity and avoid immunopathology, from proteins present in the Leishmania secretome, major players in host/pathogen interactions and known to induce Th1 cellular responses. Total excreted/secreted antigens of the six main pathogenic species were analysed by Mass-Spectrometry enabling the identification of conserved vaccine candidates. Through two different approaches, we selected 28 previously described antigen candidates, attesting to the vaccinal potential of the parasite's secretome, and 24 novel proteins based on conservation among species and lack of homology to human proteins. We propose an innovative in silico analysis of selected proteins to predict and select CTL- and Th1-inducing epitopes, subsequently synthesized as peptides. The proposed candidates will be tested experimentally with samples from naive, asymptomatic and healed individuals, providing the valuable opportunity to directly infer on their ability to mimic protective immune responses and elicit a strong and long-lasting immunity against leishmaniasis.