Antigen of hybrid M protein and carrier for group a streptococcal vaccine

Abstract

Recombinant hybrid streptococcal M protein antigens are provided which elicit protective antibodies against Group A streptococci and prevent rheumatic fever. Recombinant hybrid genes that encode the antigen are provided. Vaccine compositions and methods of administering the compositions are provided to elicit immunity against Group A streptococci.

1 .- 21 . (canceled)  
     
     
         22 . A recombinant hybrid Streptococcal M protein antigen, comprising a carrier fused to at least one amino-terminal peptide fragment of a streptococcal M protein having an epitope that elicits opsonic antibodies to at least one group A streptococci serotype, wherein said at least one serotype is from rheumatogenic streptococci.  
     
     
         23 . The antigen according to  claim 22  wherein the carrier and said at least one amino-terminal peptide fragment of streptococcal M protein are linked in tandem by a linker comprising 1-30 amino acids.  
     
     
         24 . The antigen of  claim 22  wherein at least one serotype is at least one of serotype M1 M3, M12, M18, or M19.  
     
     
         25 . (canceled)  
     
     
         26 . A composition, comprising a biologically acceptable diluent or adjuvant and the antigen according to any one of claims  22 - 24 .  
     
     
         27 . (canceled)  
     
     
         28 . A nucleic acid molecule comprising a nucleotide sequence encoding a recombinant hybrid Streptococcal M protein antigen that comprises a carrier fused to at least one amino-terminal peptide fragment of a streptococcal M protein having an epitope that elicits opsonic antibodies to at least one group A streptococci serotype.  
     
     
         29 . A nucleic acid expression construct comprising the nucleic acid molecule according to  claim 28 , wherein a host cell containing the nucleic acid expression construct expresses the recombinant hybrid Streptococcal M protein antigen encoded by the nucleic acid molecule.  
     
     
         30 . A host cell comprising the nucleic acid expression construct according to  claim 29 .  
     
     
         31 . A method of producing a recombinant hybrid Streptococcal M protein antigen, comprising (a) growing the host cell according to  claim 30  under conditions that allow expression of a recombinant hybrid Streptococcal M protein antigen, and (b) isolating the expressed recombinant hybrid Streptococcal M protein antigen.  
     
     
         32 . (canceled)  
     
     
         33 . A method for eliciting opsonic antibodies to at least one group A streptococci, comprising administering to a patient in need thereof an effective amount of a composition comprising a biologically acceptable diluent and a non-virulent, live host cell containing a nucleic acid expression construct comprising the nucleic acid molecule according to  claim 28 , wherein the host cell containing the nucleic acid expression construct expresses the recombinant hybrid Streptococcal M protein antigen.  
     
     
         34 . The method of  claim 33  wherein the expressed recombinant hybrid Streptococcal M protein antigen is compartmentalized intracellularly within the host cell, and wherein release of the antigen from the host cell elicits opsonic antibodies.  
     
     
         35 . The method of  claim 33  wherein the carrier is the carboxy-terminal portion of a surface of a gram-positive coccus.  
     
     
         36 . The method of  claim 33  wherein the host cell is a bacterium, the bacterium being a non-cariogenic  Streptococcus mutans.    
     
     
         37 . The method of  claim 33  wherein the composition is administered orally, intranasally, or mucosally.  
     
     
         38 . A method for eliciting opsonic antibodies to at least one group A streptococci serotype, comprising administering to a patient in need thereof an effective amount of the composition according to  claim 26 .  
     
     
         39 . (canceled)  
     
     
         40 . The method for eliciting opsonic antibodies according to  claim 33  wherein the composition is administered intracutaneously, parenterally, intranasally, or mucosally.  
     
     
         41 . (canceled)