Institute Research Program II:
 
Molecular and Cellular Interactions between Parasite and Host in Onchocerciasis
 
 
Coordinator’s Summary 
 
The onchocerciasis program of the Institute has developed during the last years as a model for disease oriented research programs in molecular medicine. The work of this program links clinical studies, being performed in secluded villages in Africa, and parasitological and immunological research projects that are being performed in Hamburg. 
 
 
 
 
Immunhistochemical labelling of the cephalic space (nerve-enriched anterior portion) of an Onchocerca volvulus microfilaria in the skin using an affinity purified rabbit antibody against the recombinant Onchocerca volvulus antigen E1
 

In addition to intramural support, the generous and extensive support by the Bundesministerium für Bildung, Forschung und Technologie during the last five years allowed the Institute to become a center for onchocerciasis research. In addition the scientific work of the program, that has been presented on several national and international meetings, has received worldwide attention and recognition. The recent progress in the identification and characterization of critical parasite genes and proteins and the analysis of the human immune response against the parasite and individual parasite proteins are important prerequisites for the screening of drugs influencing parasite survival and for the development of a vaccine against the disease. 
The work performed during the last year was continued with the characterization of relevant parasite antigens and the understanding of the immune response against  Onchocerca volvulus. Several of the identified stress induced proteins were localized in the adult female worm by immunohistochemistry and by electron microscopy. Similarly, the distribution of inflammatory cells was studied in several Onchocerca species and it was shown that the distribution of mast cells was similar in all analyzed species. A ‘death domain’ motif homologous to that of human apoptotic molecules was identified in the potentially protective neural expressed protein E1 of the parasite. In addition the characterization of excretory-secretory products of microfilaria demonstrated immunoregulatory proteins that affect expression of monocyte surface markers. Immunological work concentrates on the humoral and cellular responses of infected and of putatively immune individuals, i.e. people who are exposed to the parasite but are free from disease. 
An extensive collaboration between investigators that have cloned, characterized and expressed the large panel of parasite antigens and immunologically oriented groups allows the defined characterization of the human immune response towards individual parasite antigens. Immunoreactive domains and epitopes of interesting antigens are further characterized by the use of truncated protein fragments and by the use of synthetic peptides. In this context diagnostic markers are being developed for the detection of prepatent infections and in particular for the serological identification of putatively immune individuals. The biochemical and molecular characterization of parasite antigens provides important prerequisites for vaccine development. 
The animal model studying the life cycle of Litomosoides sigmodontis in laboratory mice is now established and is used to study the immune response towards the filarial parasite and to test single, promising parasite proteins for the usefulness as vaccine candidates. In this model the immune response responsible for larval growth is being analyzed and it was shown that Th2 cells or type 2 cytokines act as effectors and control larval development. 
 

Peter F. Zipfel
 

 
Staff 

Privatdozent Dr. Peter F. Zipfel, Molecular Biology, Coordinator 
Dr. Norbert W. Brattig, Clinical Chemistry 
Prof. Dr. Dietrich W. Büttner, Parasitology 
Dr. Klaus D. Erttmann, Molecular Biology 
Dr. Michaela Gallin, Molecular Biogogy 
Dr. Kimberly Henkle-Dührsen, Parasitology 
Dr. Achim Hörauf, Medical Microbiology 
Dr. Thomas Kruppa, Parasitology 
Privatdozent Dr. Frank W. Tischendorf, Clinical Chemistry 
Prof. Dr. Rolf Walter, Parasitology 
Dr. Gabriele Wildenburg, Parasitology 
 

Doctoral Students 

Alf Domeyer, Molecular Biology 
Andrea Dötze, Medical Microbiology 
Volker Eckelt, Parasitology 
Enrique J. Gutierrez Peña, Parasitology 
Anke Haffner, Clinical Chemistry 
Simone Korten, Parasitology 
Angelika Koszarski, Molecular Biology 
Carola Nietz, Clinical Chemistry 
Ulf Rathjens, Clinical Chemistry 
Erik Schneider, Molecular Biology 
Susanne Schröder, Clinical Chemistry 
Silke Schrum, Molecular Biology 
Elizabeth Sentongo, Parasitology 
Wilson Tawe, Parasitology 
 

Support Staff 

Alexandra Bialonski, Molecular Biology 
Christiane Columbus, Molecular Biology 
Marie-Luise Eschbach, Parasitology 
Frank Geisinger, Clinical Chemistry 
Silke van Hoorn, Molecular Biology 
Eva Kampen, Molecular Biology 
Claudia Klosse, Molecular Biology 
Telse Kock, Molecular Biology 
Kerstin Nissen-Pähle, Medical Microbiology 
Gerd Ruge, Molecular Biology 
Eva Taege, Clinical Chemistry