Patent
The present invention discloses isolated nucleic acid molecules encoding a hyperimmune serum reactive antigen or a fragment thereof as well as hyperimmune serum reactive antigens or fragments thereof from S. pyogenes , methods for isolating such antigens and specific uses therefor.
1. An isolated antigenic S. pyogenes polypeptide or peptide consisting of
a) amino acids 1-48, 22-46, 22-410, 25-48, 49-70, or 181-223, of SEQ ID NO: 166, or a polypeptide consisting of at least 95% sequence identity to amino acids 1-48, 22-46, 22-410, 25-48, 49-70, or 181-223 of SEQ ID NO: 166, or a peptide consisting of amino acids 4-20, 80-89, 96-103, 105-119, 123-129, 153-160, 227-233, 236-243, 248-255, 261-269, 274-279, 283-299, 305-313, 315-332, 339-344, 349-362, 365-373, 380-388, 391-397, or 402-407 of SEQ ID NO: 166, or
b) amino acids 22-410 of SEQ ID NO: 166 with one or more amino acid substitutions selected from A214D, Y3095, T317N, V318C and K319Q, 181-223 of SEQ ID NO: 166 with an A214D amino acid substitution, 305-313 of SEQ ID NO: 166 with a Y309S amino acid substitution, or 315-332 of SEQ ID NO: 166 with one or more amino acid substitutions selected from T317N, V318C and K319Q.
2. An immunogenic composition comprising the isolated antigenic polypeptide or peptide of claim 1 .
3. The immunogenic composition of claim 2 , further comprising a pharmaceutically-acceptable carrier or excipient.
4. The immunogenic composition of claim 2 , further comprising an immunostimulatory substance.
5. The immunogenic composition of claim 4 , wherein the immunostimulatory substance is a polycationic polymer, an immunostimulatory oligodeoxynucleotide (ODN), a peptide containing at least two Lys-Leu-Lys motifs, a neuroactive compound, alum or Freund's complete or incomplete adjuvant.
6. The immunogenic composition of claim 5 , wherein the polycationic polymer is a polycationic peptide.
7. A fusion protein comprising the isolated antigenic polypeptide or peptide according to claim 1 and a heterologous peptide consisting of 1 to 10 amino acids.
8. An immunogenic composition comprising the fusion protein of claim 7 .
9. The immunogenic composition of claim 8 , further comprising a pharmaceutically-acceptable carrier or excipient.
10. The immunogenic composition of claim 8 , further comprising an immunostimulatory substance.
11. The immunogenic composition of claim 10 , wherein the immunostimulatory substance is a polycationic polymer, an immunostimulatory oligodeoxynucleotide (ODN), a peptide containing at least two Lys-Leu-Lys motifs, a neuroactive compound, alum or Freund's complete or incomplete adjuvant.
12. The immunogenic composition of claim 11 , wherein the polycationic polymer is a polycationic peptide.
13. A fusion protein comprising two or more of the isolated antigenic polypeptides or peptides of claim 1 .
14. A method of making an immunogenic composition comprising
obtaining at least one isolated antigenic S. pyogenes polypeptide or peptide of claim 1 , and
admixing the at least one isolated antigenic S. pyogenes polypeptide or peptide with a pharmaceutically-acceptable carrier or excipient.
15. A method of making a immunogenic composition comprising obtaining at least one fusion protein of claim 7 , and admixing the at least one fusion protein with a pharmaceutically-acceptable carrier or excipient.