MODULATORS OF PNEUMOCOCCAL ADHERENCE TO PULMONARY AND VASCULAR CELLS AND DIAGNOSTIC AND THERAPEUTIC APPLICATIONS.

摘要

The present invention relates to compositions and methods for preventing pneumococcal infection. In particular, this invention relates to the identification of the minimum receptor targets of pneumococcal adherence to pulmonary and vascular endothelium, and to compositions and methods for preventing such adherence. In particular, the invention relates to the ability of one or more carbohydrate entities having the following motif or motifs: a disaccharide N-acetyl-D-galactosamine 'beta'1-3Gal motif, a disaccharide N-acetyl-D-galatosamine 'beta'1-4Gal motif, and an N-acetyl-D-glucosamine motif, effective to induce elution of adherent S. pneumoniae from host cells. In particular, a composition containing all three motifs can elute about 100 percent of pneumococcal bacteria from lung epithelial cells, and from venous endothelial cells. In a particular embodiment, a pharmaceutical composition of the invention can be used to treat pneumococcal infections in which the host cells are lung epithelial cells. For use in blocking adherence to, or eluting adherent bacteria from, lung epithelial cells, the pharmaceutical composition is an aerosol formulation. The invention further provides formulations for parenteral administration for treating systemic blood-borne infections by preventing or reversing binding to venous endothelial cells. The invention further relates to methods and kits for determining the presence of pneumococci in a biological sample from a subject.