Vibro-based delivery system and immune suppression

Abstract

Embodiments described are immunosuppressant therapeutics and compositions comprising a Vop protein derived from Vibro parahaemolyticus ; and drug delivery vehicles derived from a V. parahaemolyticus expressing a mutant VopZ protein lacking amino acid residue 38-62.

What is claimed: 
     
         1 . An isolated polypeptide comprising an amino acid sequence having a percent homology of at least 90% with an amino acid sequence of SEQ. ID. NO:1, wherein the polypeptide has immunosuppression activity. 
     
     
         2 . The isolated polypeptide of  claim 1 , wherein the polypeptide suppresses interleukin-8 (IL-8) production. 
     
     
         3 . The isolated polypeptide of  claim 1 , wherein the polypeptide inhibits nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation. 
     
     
         4 . The isolated polypeptide of  claim 1 , wherein the polypeptide inhibits p65 nuclear translocation. 
     
     
         5 . The isolated polypeptide of  claim 1 , wherein the polypeptide inhibits IκBα degradation. 
     
     
         6 . The isolated polypeptide of  claim 1 , wherein the immunosuppression activity is in response to tumor necrosis factor alpha (TNF-α) and/or interleukin-1β (IL-1β) stimulation. 
     
     
         7 . The isolated polypeptide of  claim 1 , wherein the polypeptide is fused to a second protein or portions thereof, wherein the second protein is not a polypeptide of  claim 1 , or is fused/conjugated to a therapeutic molecule. 
     
     
         8 . A vector comprising a nucleic acid encoding an isolated polypeptide of  claim 1 . 
     
     
         9 . A cell comprising a vector of  claim 8 . 
     
     
         10 . An immunosuppression composition comprising an isolated polypeptide  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         11 . A method of treating an immune system disease or disorder, or suppressing a graft-versus-host disease in a subject comprising administering to a subject in need thereof a therapeutically effective amount of an isolated polypeptide of  claim 1 . 
     
     
         12 . A method of treating an immune system disease or disorder, or suppressing a graft-versus-host disease comprising administering to a subject in need thereof a therapeutically effective amount of a composition of  claim 10 . 
     
     
         13 . An isolated live attenuated bacterium comprising a nucleic acid encoding a mutant VopZ protein. 
     
     
         14 . The isolated bacterium of  claim 13  is of  Vibro  spp. 
     
     
         15 . The isolated bacterium of  claim 14  is  Vibro parahaemolyticus.    
     
     
         16 . The isolated bacterium of  claim 13 , wherein the encoded VopZ protein is lacking at least the amino acid residues 38-62 of SEQ. ID. NO:1. 
     
     
         17 . The isolated bacterium of  claim 13 , wherein the encoded VopZ protein comprising an amino acid sequence having a percent homology of at least 90% with an amino acid sequence of SEQ. ID. NO:2. 
     
     
         18 . A composition comprising isolated live attenuated bacteria of  claim 13  and a pharmaceutically acceptable carrier. 
     
     
         19 . A delivery vehicle for introducing an extraneous protein into animal cells comprising isolated live attenuated bacteria of  claim 13 .