Immunoparasitology - Bruno Gottstein & Junhua Wang

Alveolar echinococcosis (AE) is one of the clinically most severe zoonotic helminthic diseases in humans. It is characterized by a chronic progressive hepatic damage caused by the continuous proliferation of the larval stage (metacestode) of Echinococcus multilocularis. By increasing evidence, AE appears today as an opportunistic infection, based on an increased number of AE patients having received immunosuppressive therapy that renders them more susceptible to develop AE. Mechanistically, AE patients exhibit a periparasitic down-regulated immune response that is triggered by the parasite and orients local immunity towards anergy.

 

Since Treg cells play a crucial role in disease (AE) progression, there is an inherent interest in co-inhibitory receptors that could be exploited for inhibiting Treg effector functions. In this immunological context, anti-PD-L1 administration yields in a decreased parasite development. This becomes apparent by a reduced size of liver lesions in a murine model of oral (primary) infection, and a significantly decreased parasite load in a murine model of intraperitoneal (secondary) infection. Conclusively, new immunotherapeutical tools may be developed, with the aim to reverse the periparasitic anergic situtation and thus to allow immunity to curatively control AE.

Immunomodulatory processes are experimentally studied in appropriate murine models in close collaboration with Anne-Pauline Bellanger (CHU Besançon) and Peter Deplazes (Vetsuisse Zürich), an in clinical studies (human AE-patients) with Guido Beldi (Inselspital Bern), Laurence Millon (CHU Besançon) and Beate Grüner (University Hospital Ulm).

 

One putative option to prevent AE is to immunize intermediate hosts with appropriate vaccines. Two vaccine candidates have been developed (recEm14-3-3 and recEm95) in Bern, which are presently being experimentally used in primate populations that exhibit high risk of infection and disease. One group consists of a population of Macaca fascicularis at the Zoo of Basel. The same vaccination strategy is experimentally investigated at the German Primate Center in Göttingen with a group of Macaca mulatta. Furthermore, primates at the Vietnamese 'Endangered Primate Rescue Center (EPRC)' exhibit health problems due to infection with Echinococcus ortleppi, a parasite closely related to E. multilocularis. A specific vaccine (Eo95) was synthesized in Bern, and is now being experimentally assessed, in collaboration with Caroline Rowley of EPRC, to protect endangered Langur primates against this parasitic disease.