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Novel technology for the molecular characterization of habitats of intracellular pathogens and its use for the development of a live vaccine against Leishmaniases.

Final Activity Report Summary - PATHOGEN HABITATS (Novel technology for the molecular characterization of habitats of intracellular pathogens ...)

This project aimed to develop a novel methodology to isolate habitats of intracellular pathogens for comprehensive molecular analysis of proteins contributing to these compartments. Unicellular Leishmania parasites, the causative agents of Leishmaniases, neglected diseases endemic in Southern European countries and affecting more than 12 million people worldwide, were at the focus of this work. These pathogens live within host cells in membrane delimited, so-called parasitophorous vacuoles. They were chosen as a model pathogen to develop the methodology, deploy it to analyse the parasite's intracellular habitat and adaptation to it, and to exploit the knowledge thus gained for the development of an affordable vaccine against these diseases.

Over the time of three and a half years the necessary methodology was developed and all detectable proteins were catalogued. This included proteins that the parasites express in this compartment, as well as proteins found in the vacuole and making up the host cell-derived membrane border of the habitat. Overall, more than 500 parasite and 900 host cell-derived proteins were identified. The latter constitute the first comprehensive description of membrane proteins delimiting a pathogen's habitat within a host cell. This is crucial for understanding the intimate interaction in this case of a parasite with its host cell. This list of parasite proteins predicted particular metabolic adaptations of these organisms to intracellular life. This created new knowledge that can be exploited to define potential drug targets and knowledge useful to select parasite proteins for the development of novel vaccines. As part of the project we developed such novel - currently experimental - vaccines and evaluated them in animal models to seek pre-clinical evidence for their efficacy. These studies identified two promising parasite proteins, vaccine candidates that will be developed further and may be part of a future vaccine made to protect people living in or travelling to endemic areas. These project results were and will be shared with the interested community in detail through scientific publications.

A team of five scientists was funded by this project. This created the opportunity for two early stage researchers to successfully complete their PhDs and for two post-doctoral scientists to gain further qualification. All continue to pursue scientific careers currently within Europe. The team leader was recruited to head and establish a parasitology unit in a public health institute of a European Union member state. Thus, the project nurtured not only significant scientific progress but had also a lasting beneficial impact on the professional careers of all team members.