title: Prevention and Immunotherapy of Secondary Murine Alveolar Echinococcosis Employing Recombinant EmP29 Antigen.
abstract: Alveolar echinococcosis (AE) is caused by infection with the larval stage of the tapeworm Echinococcus multilocularis. An increasing understanding of immunological events that account for the metacestode survival in human and murine AE infection prompted us to undertake explorative experiments tackling the potential of novel preventive and/or immunotherapeutic measures. In this study, the immunoprotective and immunotherapeutic ability of recombinant EmP29 antigen (rEmP29) was assessed in mice that were intraperitoneally infected with E. multilocularis metacestodes. For vaccination, three intraperitoneal injections with 20μg rEmP29 emulsified in saponin adjuvants were applied over 6 weeks. 2 weeks after the last boost, mice were infected, and at 90 days post-infection, rEmP29-vaccinated mice exhibited a median parasite weight that was reduced by 75% and 59% when compared to NaCl- or saponin-treated control mice, respectively. For immunotherapeutical application, the rEmP29 (20μg) vaccine was administered to experimentally infected mice, starting at 1 month post-infection, three times with 2 weeks intervals. Mice undergoing rEmP29 immunotherapy exhibited a median parasite load that was reduced by 53% and 49% when compared to NaCl- and saponin-treated control mice, respectively. Upon analysis of spleen cells, both, vaccination and treatment with rEmP29, resulted in low ratios of Th2/Th1 (IL-4/IFN-γ) cytokine mRNA and low levels of mRNA coding for IL-10 and IL-2. These results suggest that reduction of the immunosuppressive environment takes place in vaccinated as well as immunotreated mice, and a shift towards a Th1 type of immune response may be responsible for the observed increased restriction of parasite growth. The present study provides the first evidence that active immunotherapy may present a sustainable route for the control of AE.
authors.affiliation: Institute of Parasitology, University of Bern, Bern, Switzerland; Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland; Faculty of Pharmacy, Department of Clinical Biology B, Laboratory of Medical and Molecular Parasitology-Mycology (LR12ES08), University of Monastir, Monastir, Tunisia.
authors.forename: Ghalia
authors.initials: G
authors.lastname: Boubaker
authors.affiliation: Institute of Parasitology, University of Bern, Bern, Switzerland.
authors.forename: Andrew
authors.initials: A
authors.lastname: Hemphill
authors.affiliation: Institute of Parasitology, University of Bern, Bern, Switzerland.
authors.forename: Cristina Olivia
authors.initials: CO
authors.lastname: Huber
authors.affiliation: Institute of Parasitology, University of Bern, Bern, Switzerland.
authors.forename: Markus
authors.initials: M
authors.lastname: Spiliotis
authors.affiliation: Faculty of Pharmacy, Department of Clinical Biology B, Laboratory of Medical and Molecular Parasitology-Mycology (LR12ES08), University of Monastir, Monastir, Tunisia.
authors.forename: Hamouda
authors.initials: H
authors.lastname: Babba
authors.affiliation: Institute of Parasitology, University of Bern, Bern, Switzerland.
authors.forename: Bruno
authors.initials: B
authors.lastname: Gottstein
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D004443:Echinococcosis; D004444:Echinococcosis, Hepatic / Q000276:immunology / Q000517:prevention & control*; D048210:Echinococcus multilocularis / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D007167:Immunotherapy / Q000379:methods*; D051379:Mice; D059208:Parasite Load; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology; D014614:Vaccines, Synthetic / Q000494:pharmacology*
chemical_list: D000947:Antigens, Helminth; D016207:Cytokines; D017931:DNA Primers; C406723:P-29 antigen; D014614:Vaccines, Synthetic