Recombinant Bacterium and Uses Thereof

Abstract

The present invention relates to a recombinant bacterium expressing an antigen that is translocated to the cytosol of a host organism, and uses thereof. To this end, the present invention provides a recombinant bacterium comprising a nucleic acid encoding an antigen that is translocated to the cytosol of a host cell utilizing Type Ill secretion system. The recombinant bacterium is generally chosen from intracellular pathogens that reside in the phagosome and fail to induce rapid T cell activation. The translocated antigen may be a viral antigen, a bacterial antigen, or a tumour antigen. Methods of imparting immunity using the recombinant bacterium are also provided.

1 . A recombinant  Salmonella  bacterium comprising a nucleic acid encoding a fusion protein comprising:
 a) a tumour antigen, a viral antigen, or bacterial antigen; and   b) an N-terminal secretion signal from a type III secretion domain;   wherein the N-terminal secretion signal consists of the sequence set forth in SEQ ID NO: 2.   
     
     
         2 . The recombinant bacterium of  claim 1 , wherein the fusion protein further comprises a chaperone. 
     
     
         3 . The recombinant bacterium of  claim 2 , wherein the chaperone is a component of a type III secretion system. 
     
     
         4 . The recombinant bacterium of  claim 3 , wherein the chaperone is SycE or HSP70. 
     
     
         5 . The recombinant bacterium of  claim 1 , wherein the nucleic acid is comprised in a vector. 
     
     
         6 . The recombinant bacterium of  claim 5 , wherein the vector is a pHR vector. 
     
     
         7 . The recombinant bacterium of  claim 5 , wherein the vector is pHR-241. 
     
     
         8 . The recombinant bacterium of  claim 1 , wherein the tumour antigen is tyrosinase related protein 2 (TRP-2), MART-1, melanoma associated antigen 1 (MAGE1), Her-2/neu, or gp100.