Vaccines Comprising Mycobacterium Leprae Polypeptides for the Prevention, Treatment, and Diagnosis of Leprosy

Abstract

Compositions and methods for preventing, treating and detecting leprosy are disclosed. The compositions generally comprise polypeptides comprising one or more Mycobacterium leprae antigens as well as polynucleotides encoding such polypeptides.

1 . A method for stimulating an immune response in a mammal comprising administering to a mammal in need thereof a fusion polypeptide comprising  Mycobacterium leprae  ( M. leprae ) antigens ML2028, ML2055, and ML2380, or  M. leprae  antigens having at least 90% amino acid sequence identity to ML2028, ML2055, and ML2380. 
     
     
         2 . The method of  claim 1 , wherein the fusion polypeptide further comprises  M. leprae  antigen ML2531 or an  M. leprae  antigen having at least 90% amino acid sequence identify to ML2531. 
     
     
         3 . The method of  claim 1 , further comprising administering to the mammal  M. bovis  BCG vaccine. 
     
     
         4 . The method of  claim 1 , wherein  M. bovis  BCG vaccine was previously administered to the mammal. 
     
     
         5 . (canceled) 
     
     
         6 . (canceled) 
     
     
         7 . The method of  claim 1 , wherein the mammal is a human healthy household contact of a human identified as being infected with  M. leprae , the mammal has been infected by  M. leprae , or the mammal exhibits signs or symptoms of infection by  M. leprae.    
     
     
         8 . (canceled) 
     
     
         9 . (canceled) 
     
     
         10 . The method of  claim 1 , wherein from 1 ug to about 20 ug or from 1 ug to about 10 ug of the composition is administered to the mammal per dose. 
     
     
         11 . (canceled) 
     
     
         12 . (canceled) 
     
     
         13 . A method for treating or reducing the time course of chemotherapy against a  Mycobacterium leprae  ( M. leprae ) infection in a mammal, the method comprising administering to a mammal having an  M. leprae  infection a fusion polypeptide comprising  M. leprae  antigens ML2028, ML2055, and ML2380, or  M. leprae  antigens having at least 90% amino acid sequence identity to ML2028, ML2055, and ML2380. 
     
     
         14 . The method of  claim 13 , wherein the fusion polypeptide further comprises  M. leprae  antigen ML2531 or an  M. leprae  antigen having at least 90% amino acid sequence identify to ML2531. 
     
     
         15 . The method of  claim 13 , further comprising administering to the mammal one or more chemotherapeutic agents. 
     
     
         16 . The method of  claim 15 , wherein the one or more chemotherapeutic agents comprise one or more agents selected from the group consisting of dapsone, rifampicin, clofazimine, ofloxacin, minocycline, gatifloxacin, linezolid, and PA 824. 
     
     
         17 . The method of  claim 15 , wherein: (i) the mammal is first administered one or more chemotherapeutic agents over a period of time and subsequently administered the composition, (ii) the mammal is first administered the composition and subsequently administered one or more chemotherapeutic agents over a period of time; (iii) administration of the one or more chemotherapeutic agents and the composition is concurrent. 
     
     
         18 . (canceled) 
     
     
         19 . (canceled) 
     
     
         20 . The method of  claim 13 , further comprising administering the composition to the mammal one or more subsequent times. 
     
     
         21 . The method of  claim 13 , further comprising administering to the mammal  M. bovis  BCG vaccine. 
     
     
         22 . The method of  claim 13 , wherein  M. bovis  BCG vaccine was previously administered to the mammal. 
     
     
         23 - 29 . (canceled) 
     
     
         30 . The method of  claim 13 , wherein the mammal is infected with a multidrug resistant  M. leprae.    
     
     
         31 - 33 . (canceled) 
     
     
         34 . The method of  claim 13 , wherein the time course of chemotherapy is shortened to no more than about 3 months, about 5 months, or about 7 months. 
     
     
         35 . (canceled) 
     
     
         36 . The method of  claim 13 , wherein from 1 ug to about 20 ug or from 1 ug to about 10 ug of the composition is administered to the mammal per dose. 
     
     
         37 . The method of  claim 13 , further comprising administering the immunostimulant GLA is administered to the mammal. 
     
     
         38 . A method for detecting  Mycobacterium leprae  ( M. leprae ) infection in a biological sample, comprising:
 (a) contacting a biological sample with a fusion polypeptide comprising  M. leprae  antigens ML2028, ML2055, and ML2380, or  M. leprae  antigens having at least 90% amino acid sequence identity to ML2028, ML2055, and ML2380; and   (b) detecting in the biological sample the presence of antibodies that bind to the fusion polypeptide, thereby detecting  M. leprae  infection in a biological sample.   
     
     
         39 . The method of  claim 38 , wherein the fusion polypeptide further comprises  M. leprae  antigen ML2531 or an  M. leprae  antigen having at least 90% amino acid sequence identify to ML2531. 
     
     
         40 - 46 . (canceled)