Immunogenic compositions are provided herein that are useful for inducing an immune response specific against group A streptococcus (GAS). Immunogenic compositions provided herein are multivalent and comprise a plurality of immunogenic peptides or fusion polypeptides comprising the immunogenic peptides that induce an immune response against GAS. The immunogenic compositions provided herein induce an immune response against the GAS serotypes represented by an immunogenic peptide (derived from an M protein or Spa protein) comprised within the immunogenic composition and also induce an immune response against serotypes that are unrepresented by any immunogenic peptide included in the immunogenic composition. Methods for using the compositions for inducing an immune response against GAS and for treating or reducing the likelihood of occurrence of a GAS infection are also provided.
1. An immunogenic composition comprising at least 31 immunogenic peptides, wherein each immunogenic peptide is different and comprises at least 25 contiguous amino acids from the amino terminal portion of a different M protein or a Spa protein, wherein each different M protein is independently selected from the M protein of group A streptococcus (GAS) serotype 1, 2, 3, 4, 5, 6, 11, 12, 14, 18, 19, 22, 24, 28, 29, 44, 49, 58, 73, 75, 77, 78, 81, 82, 83, 87, 89, 92, 114, and 118, and the Spa protein is from GAS serotype 18.
2. The immunogenic composition of claim 1 , wherein at least four of the different immunogenic peptides are linked in tandem to form a fusion polypeptide.
3. The immunogenic composition of claim 1 comprising a first fusion polypeptide, a second fusion polypeptide, a third fusion polypeptide, and a fourth fusion polypeptide that each comprises at least six of the different immunogenic peptides linked in tandem.
4. The immunogenic composition of claim 3 , wherein the first fusion polypeptide comprises eight of the different immunogenic peptides linked in tandem, wherein each of the eight immunogenic peptides comprises at least 25 contiguous amino acids from the amino terminal portion of a different M protein or the Spa protein, wherein each different M protein is independently selected from the M protein of GAS serotype 1, 2, 3, 6, 12, 18, and 28, and the Spa protein is from GAS serotype 18.
5. The immunogenic composition of claim 4 , wherein the immunogenic peptide located at the carboxy terminal end of the first fusion polypeptide is a duplicate of the immunogenic peptide located at the amino terminal end of the first fusion polypeptide.
6. The immunogenic composition of claim 3 , wherein the second fusion polypeptide comprises eight of the different immunogenic peptides linked in tandem, and wherein each of the eight immunogenic peptides comprises at least 25 contiguous amino acids from the amino terminal portion of a different M protein independently selected from the M protein of GAS serotype 4, 5, 11, 14, 19, 24, 29, and 75.
7. The immunogenic composition of claim 6 , wherein the immunogenic peptide located at the carboxy terminal end of the second fusion polypeptide is a duplicate of the immunogenic peptide located at the amino terminal end of the second fusion polypeptide.
8. The immunogenic composition of claim 3 , wherein the third fusion polypeptide comprises eight of the different immunogenic peptides linked in tandem, and wherein each of the eight immunogenic peptides comprises at least 25 contiguous amino acids from the amino terminal portion of a different M protein independently selected from the M protein of GAS serotype 22, 44, 58, 73, 77, 78, 89, and 118.
9. The immunogenic composition of claim 8 , wherein the immunogenic peptide located at the carboxy terminal end of the third fusion polypeptide is a duplicate of the immunogenic peptide located at the amino terminal end of the third fusion polypeptide.
10. The immunogenic composition of claim 3 , wherein the fourth fusion polypeptide comprises seven of the different immunogenic peptides linked in tandem, and wherein each of the seven immunogenic peptides comprises at least 25 contiguous amino acids from the amino terminal portion of a different M protein independently selected from the M protein of GAS serotype 49, 81, 82, 83, 87, 92, and 114.
11. The immunogenic composition of claim 10 , wherein the immunogenic peptide located at the carboxy terminal end of the fourth fusion polypeptide is a duplicate of the immunogenic peptide located at the amino terminal end of the fourth fusion polypeptide.
12. The immunogenic composition of claim 1 , wherein each of the immunogenic peptides comprises (a) the at least 25 contiguous amino acids from the amino terminal portion of the different M protein or the Spa protein in duplicate; (b) at least 40 contiguous amino acids from the amino terminal portion of the different M protein or the Spa protein; (b) at least 45 contiguous amino acids from the amino terminal portion of the different M protein or the Spa protein; or (d) at least 50 contiguous amino acids from the amino terminal portion of the different M protein or the Spa protein.
13. The immunogenic composition of claim 1 , further comprising a pharmaceutically acceptable excipient.
14. The immunogenic composition of claim 13 , further comprising a pharmaceutically acceptable adjuvant.
15. A method for inducing an immune response against group A streptococcus in a subject, comprising administering to the subject the immunogenic composition of claim 1 .
16. The method of claim 15 , wherein at least four of the different immunogenic peptides are linked in tandem to form a fusion polypeptide.
17. The method of claim 15 , wherein the immunogenic composition comprises a first fusion polypeptide, a second fusion polypeptide, a third fusion polypeptide, and a fourth fusion polypeptide that each comprises at least six of the different immunogenic peptides linked in tandem.
18. The method of claim 17 , wherein the first fusion polypeptide comprises eight of the different immunogenic peptides linked in tandem, wherein each of the eight immunogenic peptides comprises at least 25 contiguous amino acids from the amino terminal portion of a different M protein or the Spa protein, wherein each different M protein is independently selected from the M protein of GAS serotype 1, 2, 3, 6, 12, 18, and 28, and the Spa protein is from GAS serotype 18.
19. The method of claim 18 , wherein the immunogenic peptide located at the carboxy terminal end of the first fusion polypeptide is a duplicate of the immunogenic peptide located at the amino terminal end of the first fusion polypeptide.
20. The method of claim 17 , wherein the second fusion polypeptide comprises eight of the different immunogenic peptides linked in tandem, and wherein each of the eight immunogenic peptides comprises at least 25 contiguous amino acids from the amino terminal portion of a different M protein independently selected from the M protein of GAS serotype 4, 5, 11, 14, 19, 24, 29, and 75.
21. The method of claim 20 , wherein the immunogenic peptide located at the carboxy terminal end of the second fusion polypeptide is a duplicate of the immunogenic peptide located at the amino terminal end of the second fusion polypeptide.
22. The method of claim 17 , wherein the third fusion polypeptide comprises eight of the different immunogenic peptides linked in tandem, and wherein each of the eight immunogenic peptides comprises at least 25 contiguous amino acids from the amino terminal portion of a different M protein independently selected from the M protein of GAS serotype 22, 44, 58, 73, 77, 78, 89, and 118.
23. The method of claim 22 , wherein the immunogenic peptide located at the carboxy terminal end of the third fusion polypeptide is a duplicate of the immunogenic peptide located at the amino terminal end of the third fusion polypeptide.
24. The method of claim 17 , wherein the fourth fusion polypeptide comprises seven of the different immunogenic peptides linked in tandem, and wherein each of the seven immunogenic peptides comprises at least 25 contiguous amino acids from the amino terminal portion of a different M protein independently selected from the M protein of GAS serotype 49, 81, 82, 83, 87, 92, and 114.
25. The method of claim 24 , wherein the immunogenic peptide located at the carboxy terminal end of the fourth fusion polypeptide is a duplicate of the immunogenic peptide located at the amino terminal end of the fourth fusion polypeptide.
26. The method of claim 15 , wherein each of the immunogenic peptides comprises (a) the at least 25 contiguous amino acids from the amino terminal portion of the different M protein or the Spa protein in duplicate; (b) at least 40 contiguous amino acids from the amino terminal portion of the different M protein or the Spa protein; (b) at least 45 contiguous amino acids from the amino terminal portion of the different M protein or the Spa protein; or (d) at least 50 contiguous amino acids from the amino terminal portion of the different M protein or the Spa protein.
27. The method of claim 15 , wherein the immunogenic composition further comprises a pharmaceutically acceptable excipient.
28. The method of claim 27 , wherein the immunogenic composition further comprises a pharmaceutically acceptable adjuvant.