Vaccines for prevention and treatment of tuberculosis

Abstract

The present invention provides new immunological compositions and vaccines comprising selected M. tuberculosis antigens and antigenic peptides as well as nucleic acids encoding said antigens for use in the prevention, prophylaxis and treatment of mycobacterial infection, especially tuberculosis. In particular the invention provides recombinant BCG based vaccines in which one or more of the selected M. tuberculosis antigens are over expressed. The invention further provides isolated peptides for use in methods for diagnosing, characterizing, or classifying mycobacterial infections.

1 . A vaccine or an immunological compositions comprising one or more polypeptides selected from
 i) the polypeptide SEQ ID NO: 1,   ii) a polypeptide being a functional variant of the polypeptide i) which has an amino acid sequence which is more than 50%, more than 75%, such as more than 80%, more than 90%, or even more preferably more than 95% identical to the sequence SEQ ID NO: 1,   iii) The polypeptide SEQ ID NO:2,   iv) a polypeptide being a functional variant of the polypeptide iii) which has an amino acid sequence which is more than 50%, more than 75%, such as more than 80%, more than 90%, or even more preferably more than 95% identical to the sequence SEQ ID NO:2,   v) the polypeptide SEQ ID NO:3,   vi) a polypeptide being a functional variant of the polypeptide v) which has an amino acid sequence which is more than 50%, more than 75%, such as more than 80%, more than 90%, or even more preferably more than 95% identical to the sequence SEQ ID NO:3, and   vii) a polypeptide comprising one or more functional fragment of any one of the polypeptides (i)-(vi), said fragment comprising an immunogenic portion, e.g. a T-cell epitope, of said polypeptide.   
     
     
         2 . The vaccine or immunological composition according to  claim 1  comprising two or more polypeptides selected from said polypeptides (i)-(vii). 
     
     
         3 . A vaccine or an immunological compositions comprising one or more nucleic acid sequences selected from nucleic acids encoding one or more polypeptides selected from
 i) the polypeptide SEQ ID NO: 1,   ii) a polypeptide being a functional variant of the polypeptide i) which has an amino acid sequence which is more than 50%, more than 75%, such as more than 80%, more than 90%, or even more preferably more than 95% identical to the sequence SEQ ID NO: 1,   iii) the polypeptide SEQ ID NO:2,   iv) a polypeptide being a functional variant of the polypeptide iii) which has an amino acid sequence which is more than 50%, more than 75%, such as more than 80%, more than 90%, or even more preferably more than 95% identical to the sequence SEQ ID NO:2,   v) the polypeptide SEQ ID NO:3,   vi) a polypeptide being a functional variant of the polypeptide v) which has an amino acid sequence which is more than 50%, more than 75%, such as more than 80%, more than 90%, or even more preferably more than 95% identical to the sequence SEQ ID NO:3, and   vii) a polypeptide comprising one or more functional fragment of any one of the polypeptides (i)-(vi), said fragment comprising an immunogenic portion, e.g. a T-cell epitope of said polypeptide.   
     
     
         4 . The vaccine or immunological composition according to  claim 3  comprising two or more nucleic acid sequences selected from nucleic acids encoding polypeptides selected from said polypeptides (i)-(vii). 
     
     
         5 . A recombinant Bacille Calmette-Guerin (BCG) comprising one or more nucleic acid sequence selected from nucleic acids encoding one or more polypeptides selected from
 i) the polypeptide SEQ I D NO: 1,   ii) a polypeptide being a functional variant of the polypeptide i) which has an amino acid sequence which is more than 50%, more than 75%, such as more than 80%, more than 90%, or even more preferably more than 95% identical to the sequence SEQ ID NO: 1,   iii) the polypeptide SEQ ID NO:2,   iv) a polypeptide being a functional variant of the polypeptide iii) which has an amino acid sequence which is more than 50%, more than 75%, such as more than 80%, more than 90%, or even more preferably more than 95% identical to the sequence SEQ ID NO:2,   v) the polypeptide SEQ ID NO:3,   vi) a polypeptide being a functional variant of the polypeptide v) which has an amino acid sequence which is more than 50%, more than 75%, such as more than 80%, more than 90%, or even more preferably more than 95% identical to the sequence SEQ ID NO:3, and   vii) a polypeptide comprising one or more functional fragment of any one of the polypeptides (i)-(vi), said fragment comprising an immunogenic portion, e.g. a T-cell epitope, of said polypeptide, wherein said nucleic acid sequences are overexpressed.   
     
     
         6 . The recombinant Bacille Calmette-Guerin (BCG) according to  claim 5  comprising two or more nucleic acid sequences selected from nucleic acids encoding polypeptides selected from said polypeptides (i)-(vii). 
     
     
         7 . A vaccine or an immunological composition comprising a recombinant Bacille Calmette-Guerin (BCG) according to  claim 5 . 
     
     
         8 . An isolated peptide of between 7 to 20 amino acids in length comprising a sequence of at least 7 consecutive amino acids derived from the sequence of a polypeptide selected from the polypeptides
 a) Putative cyclopropane-fatty-acyl-phospholipid synthase (GenBank Accession No. CAA17404) as shown in SEQ ID NO:1,   b) Possible glycosyltransferase (GenBank Accession No. CAB05418) as shown in SEQ ID NO:2, and   c) Possible glycosyltransferase (GenBank Accession No. CAB05419) as shown in SEQ ID NO:3.   
     
     
         9 . A peptide according to  claim 8  selected from the group of peptides consisting of the peptides SEQ ID NO: 4 to 118. 
     
     
         10 . A peptide according to  claim 9  selected from the group of peptides consisting of the peptides 
       
         
           
                 
                 
               
                     
                   SEQ ID NO: 4 
                 
                     
                   VLAGSVDEL, 
                 
                     
                     
                 
                     
                   SEQ ID NO: 5 
                 
                     
                   KYIFPGGLL, 
                 
                     
                     
                 
                     
                   SEQ ID NO: 6 
                 
                     
                   RMWELYLAY, 
                 
                     
                     
                 
                     
                   SEQ ID NO: 7 
                 
                     
                   AASAAIANR, 
                 
                     
                     
                 
                     
                   SEQ ID NO: 8 
                 
                     
                   ALADLPVTV, 
                 
                     
                     
                 
                     
                   SEQ ID NO: 9 
                 
                     
                   KYIAADRKI, 
                 
                     
                     
                 
                     
                   SEQ ID NO: 10 
                 
                     
                   SARLAGIPY, 
                 
                     
                     
                 
                     
                   SEQ ID NO: 11 
                 
                     
                   AAPEPVARR, 
                 
                     
                     
                 
                     
                   SEQ ID NO: 12 
                 
                     
                   ATLGSSGGK, 
                 
                     
                     
                 
                     
                   SEQ ID NO: 13 
                 
                     
                   ATAGRNHLK, 
                 
                     
                     
                 
                     
                   SEQ ID NO: 14 
                 
                     
                   SIIIPTLNV, 
                 
                     
                     
                 
                     
                   SEQ ID NO: 15 
                 
                     
                   PYNLRYRVL, 
                 
                     
                     
                 
                     
                   SEQ ID NO: 16 
                 
                     
                   IVLVRRWPK, 
                 
                     
                   and 
                 
                     
                     
                 
                     
                   SEQ ID NO: 17 
                 
                     
                   LVYGDVIMR. 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         11 . A vaccine or immunological composition comprising one or more of the peptides according to  claim 8 . 
     
     
         12 . A method for immunizing a subject against infection caused by a mycobacterial species or for eliciting an immune response to a mycobacterial species in said subject, comprising the step of administering to said subject a vaccine composition or an immunological composition according to  claim 1 . 
     
     
         13 . A method for treating a subject having an infection caused by a mycobacterial species comprising the step of administering to said subject a vaccine composition or an immunological composition according to  claim 1 . 
     
     
         14 . A method for diagnosing, characterizing, or classifying a mycobacterial infection the method comprising the use of one or more peptides according to  claim 8 . 
     
     
         15 . The method according to  claim 14 , wherein the peptide is a peptide comprising a sequence corresponding to any of SEQ ID NOs 4-118. 
     
     
         16 . A method for diagnosing, characterizing, or classifying a mycobacterial infection the method comprising the use of one or polypeptides polypeptide selected from
 i) the polypeptide SEQ I D NO: 1,   ii) a polypeptide being a functional variant of the polypeptide i) which has an amino acid sequence which is more than 50%, more than 75%, such as more than 80%, more than 90%, or even more preferably more than 95% identical to the sequence SEQ ID NO: 1,   iii) the polypeptide SEQ ID NO:2,   iv) a polypeptide being a functional variant of the polypeptide iii) which has an amino acid sequence which is more than 50%, more than 75%, such as more than 80%, more than 90%, or even more preferably more than 95% identical to the sequence SEQ ID NO:2,   v) the polypeptide SEQ ID NO:3,   vi) a polypeptide being a functional variant of the polypeptide v) which has an amino acid sequence which is more than 50%, more than 75%, such as more than 80%, more than 90%, or even more preferably more than 95% identical to the sequence SEQ ID NO:3, and   vii) a polypeptide comprising one or more functional fragment of any one of the polypeptides (i)-(vi), said fragment comprising an immunogenic portion, e.g. a T-cell epitope of said polypeptide.   
     
     
         17 . The method according to  claim 14  which is an in vitro method.