Streptococcal C5A peptidase vaccine
Novel vaccines for use against β-hemolytic Streptococcus colonization or infection are disclosed. The vaccines contain an immunogenic amount of a variant of streptococcal C5a peptidase (SCP). Also disclosed is a method of protecting a susceptible mammal against β-hemolytic Streptococcus colonization or infection by administering such a vaccine. Enzymatically inactive SCP, and polynucleotides encoding these SCP proteins are further disclosed.
1. A method of protecting a susceptible mammal against (β-hemolytic Streptococcus colonization or infection comprising administering to the mammal an effective amount of a vaccine comprising an immunogenic amount of an enzymatically inactive streptococcal C5a peptidase (SCP), wherein the enzymatically inactive SCP is a variant of wild-type SCP, which amount is effective to immunize the susceptible mammal against the β-hemolytic Streptococcus colonization or infection in combination with a physiologically-acceptable, non-toxic vehicle, wherein the enzymatically inactive SCP does not exhibit enzymatic activity, wherein the enzymatically inactive SCP comprises the specificity crevice or the catalytic domain of the wild-type SCP.
2. The method of claim 1 , wherein the enzymatically inactive SCP has reduced binding activity to C5a as compared to the binding activity of the wild-type SCP to C5a.
3. The method of claim 1 , wherein the enzymatically inactive SCP is expressed from an isolated DNA sequence encoding the enzymatically inactive SCP.
4. The method of claim 1 , wherein the enzymatically inactive SCP comprises the specificity crevice of the wild-type SCP.
5. The method of claim 4 , wherein the enzymatically inactive SCP comprises contiguous amino acid residues from residue 260 to residue 417 of SEQ ID NO:1 or SEQ ID NO:23.
6. The method of claim 4 , wherein the enzymatically inactive SCP encodes one or more of amino acid residues 260, 261, 262, 415, 416 or 417of SEQ ID NO:1 or SEQ ID NO:23.
7. The method of claim 1 , wherein the enzymatically inactive SCP comprises the catalytic domain.
8. The method of claim 7 , wherein the enzymatically inactive SCP comprises contiguous amino acid residues from residue 130 to residue 512 of SEQ ID NO:1 or SEQ ID NO:23.
9. The method of claim 7 , wherein the enzymatically inactive SCP encodes one or more of amino acid residues 130, 193, 295 or 512 of SEQ ID NO:1.
10. The method of claim 1 , wherein the enzymatically inactive SCP has a modification at one or more of amino acid residues 260, 261, 262, 415, 416 or 417 of SEQ ID NO:1 or SEQ ID NO:23.
11. A method of protecting a susceptible mammal against β-hemolytic Streptococcus colonization or infection comprising administering to the mammal an effective amount of a vaccine comprising an immunogenic amount of an enzymatically inactive streptococcal C5a peptidase (SCP), wherein the SCP is a variant of wild-type SCP, which amount is effective to immunize the susceptible mammal against the β-hemolytic Streptococcus colonization or infection in combination with a physiologically-acceptable, non-toxic vehicle, wherein the SCP does not exhibit enzymatic activity, wherein the SCP has a substitution at one or more of amino acid residues 260, 261, 262, 415, 416, 417, 130, 193, 295 or 512 of SEQ ID NO:1 or SEQ ID NO:23.
12. The method of claim 11 , wherein the substitution is a conserved substitution.
13. A method of protecting a susceptible mammal against β-hemolytic Streptococcus colonization or infection comprising administering to the mammal an effective amount of a vaccine comprising an immunogenic amount of an enzymatically inactive streptococcal C5a peptidase (SCP), wherein the SCP is a variant of wild-type SCP, which amount is effective to immunize the susceptible mammal against the β-hemolytic Streptococcus colonization or infection in combination with a physiologically-acceptable, non-toxic vehicle, wherein the enzymatically inactive SCP is SCPA49D130A, SCPA49H193A, SCPA49N295A, SCPA49S512A, SCPA1D130A, SCPA1H193A, SCPA1N295A, SCPA1S512A, SCPBD130A, SCPBH193A, SCPBN295A, SCPBS512A or ΔSCPA49.
14. The method of claim 13 , wherein the enzymatically inactive SCP is SCPA1S512A.
15. The method of claim 1 , wherein the enzymatically inactive SCP does not contain a signal sequence.
16. The method of claim 1 , wherein the enzymatically inactive SCP does not contain a cell wall insert.
17. The method of claim 1 , wherein the vaccine further comprises an effective amount of an immunological adjuvant.
18. The method of claim 1 , wherein the vaccine is administered by subcutaneous or intramuscular injection.
19. The method of claim 1 , wherein the vaccine is administered by oral ingestion.
20. The method of claim 1 , wherein the vaccine is administered intranasally.
21. The method according to claim 1 , wherein the β-hemolytic Streptococcus is a group A Streptococcus , group B Streptococcus , group C Streptococcus or group G Streptococcus.
22. The method according to claim 1 , wherein the β-hemolytic Streptococcus is group A Streptococcus.
23. The method of claim 1 , wherein the enzymatically inactive SCP is a variant of SCP from group A Streptococcus , group B Streptococcus , group C Streptococcus or group G Streptococcus.
24. The method according to claim 23 , wherein the enzymatically inactive SCP is from said group A Streptococcus.
25. The method according to claim 1 , wherein the mammal is a human, dog, bovine, porcine, or horse.
26. The method according to claim 25 , wherein the mammal is human.
27. The method of claim 1 , wherein the enzymatically inactive SCP is conjugated or linked to a peptide.
28. The method of claim 1 , wherein the enzymatically inactive SCP is conjugated or linked to a polysaccharide.