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Novel gene associated with Leishmania parasite virulence: therapeutic and vaccine applications

Inventors: Hechmi LOUZIR et al.

 Description of invention:

The protozoan parasite Leishmania infects more than 10 million people in tropical and subtropical regions. Clinical manifestations of leishmania parasite infections are extremely varied and include visceral, cutaneous, diffuse cutaneous, and mucosal disease. Cutaneous leishmaniasis, caused by Leishmania (L.) major affects millions of people each year, despite numerous attempts to destroy vectors, animal reservoirs, treat infected patients and immunize animal and human populations in endemic areas. Vaccination against the disease with crude parasite preparations, or leishmanization, has been tried in areas where cutaneous leishmaniasis is endemic, though the lesion induced by this live vaccination is often complicated by prolonged ulceration and scarring. To date, vaccination with killed preparations has only been shown to be immunogenic in small numbers of people. There is a need to develop more effective anti-leishmania treatments and vaccines which would also be affordable in the developing world.

In a effort to address this need, various research groups around the world have been studying variability in Leishmania isolate virulence, which influences the course of the disease induced and the type of immune response elicited by the infected host. In the present invention, researchers at the Institut Pasteur de Tunis have screened wild Leishmania major isolates and identified isolates expressing varying levels of pathogenic potential, as demonstrated in experiments using BALB/c mice. Using differential display analysis, the researchers studied gene expression in these isolates. The researchers found particularly high expression levels of a specific cDNA in highly virulent isolates. This cDNA clone codes for a protein, named Leishmania major PDI (LmPDI), containing two regions which are identical to the sequence of the potential active site of the protein disulfide isomerase (PDI) family. Earlier work has shown that PDI plays a potential role in the pathogenicity of various microorganisms . It is believed that LmPDI represents a new therapeutic target for the development of drugs against leishmania as well as a potential component of novel immunogenic or vaccine preparations aimed at conferring immunity in humans or animals against Leishmania.

 Recent pertinent publications

Kebaier C, et al. Infect Immun 2001 Aug;69(8):4906-15

 Patent status

French patent pending

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