Chlamydial antigens

Chlamydiae are intracellular parasitic bacteria which are responsible for manifold acute and chronic diseases in animals and humans. Infections by C. trachomatis affect 500 million people in the developing countries leading to trachoma and blindness, whereas in industrialized countries C. trachomatis is most frequently diagnosed in sexually transmitted diseases. One of the most important discoveries of infectious disease biology in the last decade, however, has been the finding of another chlamydial species (Chl. pneumoniae) to be associated with cardiovascular diseases, most importantly with arteriosclerosis. Surface structures of Chlamydiae are implicated in different stages of the complex development cycle during chlamydial infections. In addition to important protein components, one major antigen located at the surface of all chlamydial species is a glycolipid containing chlamydia-specific and cross-reactive epitopes. In previous work, the crystal structures of two antibodies in complex with these carbohydrate antigens has been determined, providing the molecular basis to study protein- carbohydrate interactions in atomic detail and to increase our understanding of how antibodies manage to efficiently recognize ubiquitous bacterial carbohydrates in a specific or a non-selective manner, respectively. The project is focused on chemical synthesis of carbohydrate analogs designed to target specific (mostly ionic) interactions within the binding site of the antibodies with the intention to enhance the binding efficiency of small ligands and to mimic the native trisaccharide epitope. Furthermore, since nothing is known on changes within the trisaccharide ligand upon intramolecular ester formation, analogs mimicking these units will be prepared and used to generate and characterize monoclonal antibodies. This should allow to study the antigenic properties of the ligands and evaluate the occurrence and relevance of specific antibodies in sera. The project will be performed in combined international cooperations providing immunochemical, crystallographic and sophisticated NMR-spectroscopic techniques. The results should considerably increase the knowledge basis on antibody-carbohydrate complexes and provide new insights into the immune response during chronic and acute chlamydial infections. The antibodies will be tested for diagnostic applications and neutralization efficiency against Chlamydia, whereas the ligands could be used to potentially remove circulating immune complexes.

Chlamydiae are intracellular parasitic bacteria which are responsible for manifold acute and chronic diseases in animals and humans. Infections by C. trachomatis affect 500 million people in the developing countries leading to trachoma and blindness, whereas in industrialized countries C. trachomatis is most frequently diagnosed in sexually transmitted diseases. One of the most important discoveries of infectious disease biology in the last decade, however, has been the finding of another chlamydial species (Chl. pneumoniae) to be associated with cardiovascular diseases, most importantly with arteriosclerosis. Surface structures of Chlamydiae are implicated in different stages of the complex development cycle during chlamydial infections. In addition to important protein components, one major antigen located at the surface of all chlamydial species is a glycolipid containing chlamydia-specific and cross-reactive epitopes. In previous work, the crystal structures of two antibodies in complex with these carbohydrate antigens has been determined, providing the molecular basis to study protein- carbohydrate interactions in atomic detail and to increase our understanding of how antibodies manage to efficiently recognize ubiquitous bacterial carbohydrates in a specific or a non-selective manner, respectively. The project is focused on chemical synthesis of carbohydrate analogs designed to target specific (mostly ionic) interactions within the binding site of the antibodies with the intention to enhance the binding efficiency of small ligands and to mimic the native trisaccharide epitope. Furthermore, since nothing is known on changes within the trisaccharide ligand upon intramolecular ester formation, analogs mimicking these units will be prepared and used to generate and characterize monoclonal antibodies. This should allow to study the antigenic properties of the ligands and evaluate the occurrence and relevance of specific antibodies in sera. The project will be performed in combined international cooperations providing immunochemical, crystallographic and sophisticated NMR- spectroscopic techniques. The results should considerably increase the knowledge basis on antibody-carbohydrate complexes and provide new insights into the immune response during chronic and acute chlamydial infections. The antibodies will be tested for diagnostic applications and neutralization efficiency against Chlamydia, whereas the ligands could be used to potentially remove circulating immune complexes.