Streptococcus pneumoniae Antigens and Vaccines

Abstract

The present invention relates to novel vaccines for the prevention or attenuation of infection by Streptococcus pneumoniae . The invention further relates to isolated nucleic acid molecules encoding antigenic polypeptides of Streptococcus pneumoniae . 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 Streptococcus nucleic acids, polypeptides and antibodies in a biological sample.

1 . An isolated nucleic acid molecule comprising a polynucleotide having a nucleotide sequence at least 95% identical to a sequence selected from the group consisting of:
 (a) a nucleotide sequence encoding any of the amino acid sequences of the polypeptides shown in Table 1; and   (b) a nucleotide sequence complementary to any of the nucleotide sequences in (a).   
     
     
         2 . An isolated nucleic acid molecule 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  wherein said polynucleotide which hybridizes does not hybridize under stringent hybridization conditions to a polynucleotide having a nucleotide sequence consisting of only A residues or of only T residues. 
     
     
         3 . An isolated nucleic acid molecule comprising a polynucleotide which encodes the amino acid sequence of an epitope-bearing portion of a polypeptide having an amino acid sequence in (a) of  claim 1 . 
     
     
         4 . The isolated nucleic acid molecule of  claim 3 , wherein said epitope-bearing portion of a polypeptide has an amino acid sequence listed in Table 2. 
     
     
         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 method of making a recombinant host cell comprising introducing the recombinant vector of  claim 6  into a host cell. 
     
     
         8 . A recombinant host cell produced by the method of  claim 7 . 
     
     
         9 . A method of producing a polypeptide encoded by said isolated nucleic acid molecule comprising culturing the host cell of  claim 8  under conditions favoring expressing the heterologous polypeptide. 
     
     
         10 . A polypeptide produced according to the method of  claim 9 . 
     
     
         11 . An isolated polypeptide comprising an amino acid sequence at least 70% identical to a sequence selected from the group consisting of an amino acid sequence of any of the polypeptides described in Table 1. 
     
     
         12 . An isolated polypeptide antigen comprising an amino acid sequence of an  S. pneumoniae  epitope shown in Table 2. 
     
     
         13 . An isolated nucleic acid molecule comprising a polynucleotide with a nucleotide sequence encoding a polypeptide of  claim 9 . 
     
     
         14 . An isolated antibody that binds specifically to a polypeptide of  claim 11 . 
     
     
         15 . A hybridoma which produces an antibody according to  claim 14 . 
     
     
         16 . A vaccine, comprising:
 (1) one of more  S. pneumoniae  polypeptides selected from the group consisting of a polypeptide comprising an amino acid sequence identified in Table 1, or a fragment thereof; 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  Streptococcus  genus.   
     
     
         17 . A method of preventing or attenuating an infection caused by a member of the  Streptococcus  genus in an animal, comprising administering to said animal a polypeptide of  claim 11 , wherein said polypeptide is administered in an amount effective to prevent or attenuate said infection. 
     
     
         18 . A method of detecting  Streptococcus  nucleic acids in a biological sample obtained from an animal involving assaying for one or more nucleic acid sequences encoding  Streptococcus  polypeptides in a sample comprising:
 (a) contacting the sample with one or more of the isolated nucleic acid molecules of  claim 2 , under conditions such that hybridization occurs, and   (b) detecting hybridization of said one or more molecules to the one or more  Streptococcus  nucleic acid sequences present in the biological sample.   
     
     
         19 . A kit for detecting  Streptococcus  antibodies in a biological sample obtained from an animal, comprising:
 (a) a polypeptide of  claim 12  attached to a solid support; and   (b) detecting means.   
     
     
         20 . A method of detecting  Streptococcus  antibodies in a biological sample obtained from an animal, comprising
 (a) contacting the sample with a polypeptide of  claim 12 ; and   (b) detecting antibody-antigen complexes.