Peptide vaccines against group a streptococci

Abstract

This invention, in one aspect, relates to synthetic immunoreactive peptides. These peptides are approximately 20-25 amino acids in length which are portions of the N termini of the M proteins of the most prevalent United States (U.S.) Group A Streptococcus (GAS) serotypes. At least some of the synthetic peptides can be recognized by M type-specific antibodies and are capable of eliciting functional opsonic antibodies and/or anti-attachment antibodies without eliciting tissue cross-reactive antibodies. In another aspect, it relates to compositions or vaccines comprising these synthetic serotype-specific peptides, including polypeptides and proteins. The invention may also be isolated antibodies which are raised in response to the peptides, compositions or vaccines. The invention further relates to kits for using the peptides, compositions, or antibodies. In still further aspects, the invention also relates to methods for using the peptides, compositions, vaccines, or antibodies and methods for tailoring vaccines.

1 . A composition comprising at least one polypeptide from a Group A  Streptococcus  (GAS) M-type peptide selected from one or more of the 25 serotypes listed in Table 1, wherein the polypeptide is between 20 and 25 amino acids in length and comprises the amino acid sequence according to any one of SEQ ID NOs: 1, 2, 4-13, or 15-138. 
     
     
         2 . The composition of  claim 1 , wherein the polypeptide is a chimeric fusion protein. 
     
     
         3 . The chimeric fusion protein of  claim 2 , wherein the chimeric fusion protein comprises an amino acid sequence of one or more heterologous Group A  Streptococcus  (GAS) M-type peptides. 
     
     
         4 . The composition of  claim 1 , wherein the one or more peptides are linked to a backbone. 
     
     
         5 . The composition of  claim 1 , further comprising a pharmaceutically acceptable vehicle or carrier. 
     
     
         6 . The composition of  claim 1 , further comprising additional immune-stimulatory molecules. 
     
     
         7 . The composition of  claim 6 , wherein the additional immune-stimulatory molecules comprise GAS-based peptides, non-GAS vaccines/immunogens selected from the group consisting of  Hemophilus influenza , pertussis,  N. meningitidis , pneumococcus, and Influenzae, or adjuvants. 
     
     
         8 . The composition of  claim 1 , wherein the one or more peptides consists essentially of the amino acid sequence of any one of SEQ ID NO: 1, 2, 4-13, or 15-138. 
     
     
         9 . The composition of  claim 1 , wherein the one or more peptides consists of the amino acid sequence of any one of SEQ ID NO: 1, 2, 4-13, or 15-138. 
     
     
         10 . An immunogenic composition for eliciting a protective immune response to Group A  Streptococcus  comprising an immunogenic amount of the composition according to  claim 1 . 
     
     
         11 . The immunogenic composition of  claim 10 , wherein the immunogenic composition is capable of eliciting functional opsonic antibodies and does not contain epitopes that cross-react with tissues. 
     
     
         12 . The immunogenic composition of  claim 10 , wherein the immunogenic composition is effective in decreasing the nasopharyngeal reservoir of GAS when administered. 
     
     
         13 . A method for inducing an immune response against multiple serotypes of Group A  Streptococcus  comprising administering an immunogenic amount of the immunogenic composition of  claim 1  to a subject. 
     
     
         14 . The method of  claim 13 , wherein the administration is via injection or a mucosal delivery method. 
     
     
         15 . The method of  claim 13 , wherein the immune response is induction of opsonic antibodies and/or anti-attachment antibodies. 
     
     
         16 . The method of  claim 15 , wherein the multiple serotypes are selected from emm1, emm2, emm3, emm4, emm11, emm12, emm22, emm28, emm77, emm89, st2967, emm6, emm82, emm43, emm75, emm33, emm92, emm5, emm94, emm73, emm18, emm58, emm59, emm101, or emm41. 
     
     
         17 . An isolated polypeptide comprising the amino acid sequence according to any one of SEQ ID NO: 1, 2, 4-13, or 15-138 wherein the polypeptide is between 20 and 25 amino acids in length. 
     
     
         18 . The polypeptide of  claim 17 , wherein the polypeptide is a chimeric fusion protein. 
     
     
         19 . The chimeric fusion protein of  claim 18 , wherein the chimeric fusion protein comprises an amino acid sequence of one or more heterologous Group A  Streptococcus  (GAS) M-type peptides. 
     
     
         20 . The isolated polypeptide of  claim 17 , wherein the polypeptide consists essentially of the amino acid sequence of any one of SEQ ID NO: 1, 2, 4-13, or 15-138. 
     
     
         21 . The isolated polypeptide of  claim 17 , wherein the polypeptide consists of the amino acid sequence of any one of SEQ ID NO: 1, 2, 4-13, or 15-138.