A2M polypeptide compositions containing a non-natural bait region are disclosed. Methods of producing wild-type and variant A2M polypeptides and polynucleotides containing a non-natural bait region are also disclosed. The bait regions of the variant A2M polypeptides demonstrate enhanced protease inhibitory characteristics compared to wild-type A2M. Variant A2M polypeptides that demonstrate longer half-lives upon administration to an organism compared to wild-type A2M are disclosed. The A2M compositions are useful in treating a number of diseases and conditions including inflammation, chronic wounds, and diseases with a pathology associated with proteases.

The present invention relates to modified bacterial polypeptides having immunomodulatory and immunostimulatory activity. Most specifically, the present invention relates to modified bacterial polypeptides having an amino acid sequence selected from SEQ ID NO. 1, SEQ ID NO. 2, SEQ ID NO. 3, SEQ ID NO. 4 and SEQ ID NO. 5. The modified polypeptides are the adjuvant components of a pharmaceutical composition for eliciting an immune response against an specific antigen present in the pharmaceutical composition. In a preferred embodiment, the invention provides a pharmaceutical composition for a vaccine which comprises an adjuvant component which is any one of the modified polypeptides, one or more antigens, together with a pharmaceutically acceptable excipient.

Provided herein are IL-15 cytokine prodrugs and methods of making and using thereof.

A novel method of treating and preventing bacterial diseases is provided. In particular, the present invention relates to compositions and methods for inhibition of Gram negative, Gram positive and acid fast bacilli in general and tuberculosis (TB), Mycobacterium avium complex (MAC), and anthrax in particular. Thus, the invention relates to modulation of cellular activities, including macrophage activity, and the like. More particularly, the present invention relates to the inhibitory compounds comprising naturally occurring and man-made inhibitors of serine protease.

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.

In one aspect, the invention provides an isolated antibody, or antigen-binding fragment thereof, comprising a bioactive peptide amino acid sequence, wherein the bioactive peptide amino acid sequence is an inhibitor of the complement system and is fused to at least one of: (i) the amino terminal region of at least one of: a light chain variable region and/or a heavy chain variable region; or (ii) the carboxy terminal region of at least one of: a light chain constant region and/or a heavy chain constant region, wherein the antibody inhibits complement activation.

The invention relates to an inhibitor of Factor XII (FXII) for use in treating or preventing chronic kidney disease, renal fibrosis, glomerulosclerosis, renal scarring, ischemia/reperfusion injury in native or transplant kidneys and/or acute kidney injury, a kit for use in treating or preventing chronic kidney disease, renal fibrosis, glomerulosclerosis, renal scarring, ischemia/reperfusion injury in native or transplant kidneys, acute kidney injury, renal fibrosis as a result of rejection of a kidney transplant/allograft, and/or fibrosis of a kidney transplant/allograft as a result of rejection or recurrent underlying disease comprising one inhibitor of Factor XII, and an anti-Factor XII (FXII) antibody or antigen binding fragment thereof for use in treating or preventing chronic kidney disease, renal fibrosis, glomerulosclerosis, renal scarring, ischemia/reperfusion injury in native or transplant kidneys and/or acute kidney injury comprising one inhibitor of Factor XII.

Disclosed herein are fusion proteins comprising a truncated thrombostasin protein having at least 85% sequence homology to a thrombostasin protein, wherein the thrombostasin protein has a carboxy terminal deletion; and a fusion partner protein that is a non-thrombostasin protein. Further disclosed are vaccine compositions thrombostasin proteins having a comprising a carboxy terminal deletion, and methods for inhibiting a response to a thrombostasin protein in a host in need thereof, comprising the disclosed fusion proteins or vaccine compositions. Further disclosed are methods for the preparation of a fusion protein composition.

The present invention provides plant-made elafin-Fc fusion proteins for treating inflammatory diseases, e.g., inflammatory lung diseases. In certain embodiments, the fusion proteins comprise one or more point mutations, which confer improved properties, such as increased resistance to oxidation, cleavage, and increased half-life. The present invention additionally provides polynucleotides encoding the fusion proteins, recombinant cells and expression vectors, and transgenic plants comprising the fusion protein coding sequences. The present invention further provides methods for the production of the fusion proteins.

In one aspect, the invention provides methods of inhibiting the effects of MASP-2-dependent complement activation in a living subject. The methods comprise the step of administering, to a subject in need thereof, an amount of a MASP-2 inhibitory agent effective to inhibit MASP-2-dependent complement activation. In some embodiments, the MASP-2 inhibitory agent inhibits cellular injury associated with MASP-2-mediated alternative complement pathway activation, while leaving the classical (C1q-dependent) pathway component of the immune system intact. In another aspect, the invention provides compositions for inhibiting the effects of lectin-dependent complement activation, comprising a therapeutically effective amount of a MASP-2 inhibitory agent and a pharmaceutically acceptable carrier.