Detoxified mutants of bacterial ADP-ribosylating toxins as parenteral adjuvants

Abstract

The present invention provides parenteral adjuvants comprising detoxified mutants of bacterial ADP-ribosylating toxins, particularly those from pertussis (PT), cholera (CT), and heat-labile E. coli (LT).

1 . A method for immunizing a vertebrate subject against at least one selected antigen, the method comprising the step of parenterally administering to the vertebrate subject an immunologically effective amount of 
 a) a parenteral adjuvant comprising a polynucleotide encoding a detoxified mutant of an  E. coli  heat-labile (LT) ADP-ribosylating toxin in combination with a pharmaceutically acceptable vehicle, wherein said detoxified mutant is LT-K63; and    b) at least one selected antigen.    
     
     
         2 . The method according to  claim 1 , wherein the adjuvant and the antigen are administered subcutaneously, transcutaneously or intramuscularly.  
     
     
         3 . The method according to  claim 1 , wherein the pharmaceutically acceptable vehicle is a topical vehicle.  
     
     
         4 . The method according to  claim 1 , wherein the adjuvant and the antigen are administered transcutaneously.  
     
     
         5 . The method according to  claim 1 , wherein the adjuvant is administered to the vertebrate subject prior to administering the selected antigen.  
     
     
         6 . The method according to  claim 1 , wherein the adjuvant is administered to the vertebrate subject subsequent to administering the selected antigen.  
     
     
         7 . The method according to  claim 1 , wherein the antigen is administered to the vertebrate subject concurrent with administering the selected antigen.  
     
     
         8 . The method of  claim 1 , wherein said antigen is a viral antigen.  
     
     
         9 . The method of  claim 8 , wherein said viral antigen is selected from the group consisting of an influenza antigen, a herpes simplex virus (HSV) antigen, a human immunodeficiency virus (HIV) antigen, a cytomegalovirus (CMV) antigen, a hepatitis C virus (HCV) antigen, a delta hepatitis virus (HDV) antigen, a poliovirus antigen, a hepatitis A virus (HAV) antigen, an Epstein-Barr virus (EBV) antigen, a varicella zoster virus (VZV) antigen, and a respiratory syncytial virus (RSV) antigen.  
     
     
         10 . The method of  claim 9 , wherein said viral antigen is an influenza virus antigen.  
     
     
         11 . The method of  claim 9 , wherein said viral antigen is a poliovirus antigen.  
     
     
         12 . The method of  claim 9 , wherein said viral antigen is a RSV antigen.  
     
     
         13 . The method of  claim 1 , wherein said antigen is a bacterial antigen.  
     
     
         14 . The method of  claim 13 , wherein said bacterial antigen is selected from the group consisting of  Bordetella pertussis  antigens,  Helicobacter pylori  antigens, meningococcus A antigens, meningococcus B antigens, and meningococcus C antigens.  
     
     
         15 . The method of  claim 14 , wherein said bacterial antigen is a  Bordetella pertussis  antigen.  
     
     
         16 . The method of  claim 14 , wherein said bacterial antigen is an  Helicobacter pylori  antigen.  
     
     
         17 . The method of  claim 14 , wherein said bacterial antigen is a meningococcus A antigen.  
     
     
         18 . The method of  claim 14 , wherein said bacterial antigen is a meningococcus B antigen.  
     
     
         19 . The method of  claim 14 , wherein said bacterial antigen is a meningococcus C antigen.