| 摘要 |
Chimeric proteins are expressed, secreted or released by a bacterium to immunize against or treat a parasite, infectious disease or malignancy. The delivery vector may also be attenuated, non-pathogenic, low pathogenic, or a probiotic bacterium. The chimeric proteins include chimeras of, e.g., phage coat and/or colicin proteins, bacterial toxins and/or enzymes, autotransporter peptides, lytic peptides, multimerization domains, and/or membrane transducing (ferry) peptides. The active portion of the immunogenic chimeric proteins can include antigens against a wide range of parasites and infectious agents, cancers, Alzheimer's and Huntington's diseases, and have enhanced activity when secreted or released by the bacteria, and/or have direct anti-parasite or infectious agent activity. The activity of the secreted proteins is further increased by co-expression of a protease inhibitor that prevents degradation of the effector peptides. Addition of an antibody binding or antibody-degrading protein further prevents the premature elimination of the vector and enhances the immune response. |
| 主权项 |
1. A genetically engineered bacterium being attenuated and pharmaceutically acceptable as a non-lethal effective therapy for administration to an animal, and, having at least one first genetically engineered construct that both encodes for, and causes the bacterium to express and secrete within the animal a gene product comprising a protease inhibitor which is heterologous with respect to bacteria and configured to inhibit the at least one eukaryotic protease, wherein the genetically engineered bacterium has at least one second genetically engineered construct that both encodes for, and causes the bacterium to express a protease sensitive molecule which is heterologous with respect to bacteria, susceptible to degradation by the at least one eukaryotic protease produced by the animal which is inhibited by the protease inhibitor. |
