Lyme disease vaccines

Abstract

The present invention relates to novel vaccines for the prevention or attenuation of Lyme disease. The invention further relates to isolated nucleic acid molecules encoding antigenic polypeptides of Borrelia burgdorferi . Antigenic polypeptides are also provided, as are vectors, host cells and recombinant methods for producing the same. The invention additionally relates to diagnostic methods for detecting Borrelia gene expression.

1 . An isolated nucleic acid molecule comprising a polynucleotide having a nucleotide sequence selected from the group consisting of: 
 (a) a nucleotide sequence encoding any one of the amino acid sequences of the polypeptides shown in Table 1;    (b) a nucleotide sequence complementary to any one of the nucleotide sequences in (a);    (c) a nucleotide sequence at least 95% identical to any one of the nucleotide sequences shown in Table 1; and    (d) a nucleotide sequence at least 95% identical to a nucleotide sequence complementary to any one of the nucleotide sequences shown in Table 1.    
     
     
         2 . An isolated nucleic acid molecule of  claim 1  comprising a polynucleotide which hybridizes under stringent hybridization conditions to a polynucleotide having a nucleotide sequence identical to a nucleotide sequence in (a) or (b) of  claim 1 .  
     
     
         3 . An isolated nucleic acid molecule of  claim 1  comprising a polynucleotide which encodes an epitope-bearing portion of a polypeptide in (a) of  claim 1 .  
     
     
         4 . The isolated nucleic acid molecule of  claim 3 , wherein said epitope-bearing portion of a polypeptide comprises an amino acid sequence listed in Table 4.  
     
     
         5 . A method for making a recombinant vector comprising inserting an isolated nucleic acid molecule of  claim 1  into a vector.  
     
     
         6 . A recombinant vector produced by the method of  claim 5 .  
     
     
         7 . A host cell comprising the vector of  claim 6 .  
     
     
         8 . A method of producing a polypeptide comprising: 
 (a) growing the host cell of  claim 7  such that the protein is expressed by the cell; and    (b) recovering the expressed polypeptide.    
     
     
         9 . An isolated polypeptide comprising a polypeptide selected from the group consisting of: 
 (a) a polypeptide consisting of one of the complete amino acid sequences of Table 1;    (b) a polypeptide consisting of one the complete amino acid sequences of Table 1 except the N-terminal residue;    (c) a fragment of the polypeptide of (a) having biological activity; and    (d) a fragment of the polypeptide of (a) which binds to an antibody specific for the polypeptide of (a).    
     
     
         10 . An isolated antibody specific for the polypeptide of  claim 9 .  
     
     
         11 . A polypeptide produced according to the method of  claim 8 .  
     
     
         12 . An isolated polypeptide comprising an amino acid sequence at least 95% identical to the polypeptide of  claim 9 .  
     
     
         13 . An isolated polypeptide antigen comprising an amino acid sequence of an  B. burgdorferi  epitope shown in Table 4.  
     
     
         14 . An isolated nucleic acid molecule comprising a polynucleotide with a nucleotide sequence encoding a polypeptide of  claim 9 .  
     
     
         15 . A hybridoma which produces an antibody of  claim 10 .  
     
     
         16 . A vaccine, comprising: 
 (1) one or more  B. burgdorferi  polypeptides selected from the group consisting of a polypeptide of  claim 9;  and    (2) a pharmaceutically acceptable diluent, carrier, or excipient;    wherein said polypeptide is present, in an amount effective to elicit protective antibodies in an animal to a member of the  Borrelia  genus.    
     
     
         17 . A method of preventing or attenuating an infection caused by a member of the  Borrelia  genus in an animal, comprising administering to said animal a polypeptide of  claim 9 , wherein said polypeptide is administered in an amount effective to prevent or attenuate said infection.  
     
     
         18 . A method of detecting  Borrelia  nucleic acids in a biological sample obtained from an animal, comprising a process selected from the group consisting of: 
 (a) contacting the sample with one or more nucleic acids of  claim 1 , under conditions such that hybridization occurs, and detecting hybridization of said nucleic acids to the one or more  Borrelia  nucleic acid sequences present in the biological sample; and    (b) amplifying one or more  Borrelia  nucleic acid sequences in said sample using polymerase chain reaction, and detecting said amplified  Borrelia  nucleic acid.    
     
     
         19 . A kit for detecting  Borrelia  antibodies in a biological sample obtained from an animal, comprising 
 (a) a polypeptide of  claim 9  attached to a solid support; and    (b) detecting means.    
     
     
         20 . A method of detecting  Borrelia  antibodies in a biological sample obtained from an animal, comprising 
 (a) contacting the sample with a polypeptide of  claim 9;  and    (b) detecting antibody-antigen complexes.