Dna promoters and anthrax vaccines

Abstract

The invention is related to intracellularly induced bacterial DNA promoters and vaccines against Bacillus anthracis.

1 . An attenuated bacterium which is capable of expressing a heterologous protein, the expression of the heterologous protein being under the control of a promoter, in which the promoter is selected from the group consisting of the promoters of SEQ ID NOs: 2-8 or a functional fraction thereof. 
     
     
         2 . An attenuated bacterium according to  claim 1  which is an attenuated strain of  Salmonella.    
     
     
         3 . An attenuated bacterium according to  claim 2 , which is an attenuated strain of  Salmonella Typhi  or  Salmonella Typhimurium.   
     
     
         4 . An attenuated bacterium according to  claim 1 , in which the heterologous protein comprises an antigenic sequence derived from a virus, bacterium, fungus, yeast or parasite. 
     
     
         5 . An attenuated bacterium according to  claim 4  in which the heterologous protein is the protective antigen (PA) of  Bacillus anthracis.    
     
     
         6 . A process for the preparation of an attenuated bacterium according to  claim 1 , which process comprises transforming an attenuated bacterium with a DNA construct comprising the promoter operably linked to a DNA sequence encoding the heterologous protein. 
     
     
         7 . A composition of matter comprising a promoter, in which the promoter is selected from the group consisting of the promoters of SEQ ID NOs: 1-8 or a functional fraction thereof. 
     
     
         8 . A living attenuated vaccine, for the immunization against anthrax disease, comprising as the active component an effective dose of an attenuated galactose epimeraseless mutant strain of  S. Typhi  and a  Bacillus anthracis  protective antigen (PA) carried thereby. 
     
     
         9 . A vaccine according to  claim 8  wherein the  Bacillus anthracis  protective antigen (PA) is the wild type PA encoded by SEQ ID NO: 9 or an immunogenic fragment thereof. 
     
     
         10 . A vaccine according to  claim 9 , wherein the wild type PA is encoded by SEQ ID NO: 9. 
     
     
         11 - 15 . (canceled) 
     
     
         16 . A vaccine according to  claim 8  in freeze-dried form. 
     
     
         17 . A vaccine according to  claim 8  wherein the attenuated galactose epimeraseless mutant strain of  S. Typhi  is  S. Typhi  Ty21a. 
     
     
         18 . A method of immunizing a susceptible host against  B. anthracis  disease comprising administering to the host an effective amount of the vaccine according to  claim 8  to elicit an immunizing response.