Immunogenic composition comprising a fusion peptide derived from superantigen toxoids
The present disclosure provides immunogenic compositions useful in prevention and treatment of Staphylococcus aureus infection. In particular, the disclosure provides multivalent oligopeptides, fusion proteins comprising two or more staphylococcal superantigen (SAg) proteins, or any fragments, variants, or derivatives thereof fused together as a single polypeptide in any order.
1. An attenuated Staphylococcus aureus -derived superantigen (SAg) SEA toxoid comprising an amino acid sequence that is at least 95% identical to SEQ ID NO: 4, wherein the toxoid comprises the four mutations relative to wild-type SEA corresponding to the L48R, D70R, Y92A, and H225A mutations; and wherein the toxoid has decreased superantigenic activity and/or is less virulent than a SEA toxoid comprising SEQ ID NO: 3.
2. The attenuated SEA toxoid of claim 1 comprising an amino acid sequence at least 97% identical to SEQ ID NO: 4.
3. The attenuated SEA toxoid of claim 1 comprising SEQ ID NO: 4.
4. The attenuated SEA toxoid of claim 1 , which has less than 50% of the superantigenic activity of a SEA toxoid comprising SEQ ID NO: 3.
5. A multivalent oligopeptide comprising a fusion of two or more attenuated Staphylococcus aureus -derived superantigen (SAg) toxoids arranged in any order, wherein the SAg toxoids can be the same or different, and wherein at least one of the SAg toxoids is the SEA toxoid of claim 1 .
6. The oligopeptide of claim 5 , wherein the oligopeptide has decreased superantigenic activity and/or is less virulent than a SAg fusion protein comprising SEQ ID NO: 5.
7. The oligopeptide of claim 5 , wherein the oligopeptide has less than 50% of the superantigenic activity of a SAg fusion protein comprising SEQ ID NO: 5.
8. The oligopeptide of claim 5 , wherein the oligopeptide is completely attenuated.
9. The oligopeptide of claim 5 , comprising three or more SAg toxoids.
10. The oligopeptide of claim 5 , comprising one or more of a staphylococcal toxic shock syndrome toxin-1 (TSST-1) attenuated toxoid; a staphylococcal enterotoxin B (SEB) attenuated toxoid; or any combination thereof.
11. The oligopeptide of claim 10 , wherein the TSST-1 attenuated toxoid comprises three mutations relative to wild-type TSST-1 corresponding to the L30R, D27A, and I46A mutations and an amino acid sequence at least 95% identical to SEQ ID NO: 1; the SEB attenuated toxoid comprises three mutations relative to wild-type SEB corresponding to the L45R, Y89A, and Y94A mutations and an amino acid sequence at least 95% identical to SEQ ID NO: 2; and the SEA attenuated toxoid comprises four mutations relative to wild-type SEA corresponding to the L48R, D70R, Y92A, and H225A mutations and an amino acid sequence at least 95% identical to SEQ ID NO: 4.
12. The oligopeptide of claim 10 , wherein the TSST-1 toxoid comprises the amino acid sequence SEQ ID NO: 1; the SEB toxoid comprises the amino acid sequence SEQ ID NO: 2; and the SEA attenuated toxoid comprises the amino acid sequence SEQ ID NO: 4.
13. The oligopeptide of claim 5 , wherein the two or more SAg toxoids are each associated via a linker.
14. The oligopeptide of claim 13 , wherein the linker comprises (GGGS) n (SEQ ID NO: 13) or (GGGGS) n (SEQ ID NO: 14), wherein n is a integer from 1 to 10.
15. The oligopeptide of claim 5 comprising the amino acid sequence SEQ ID NO: 6.
16. The oligopeptide of claim 5 , further comprising a heterologous polypeptide.
17. The oligopeptide of claim 16 , wherein the heterologous polypeptide comprises an immunogen, a T-cell epitope, a B-cell epitope, a fragment thereof, or a combination thereof.
18. A composition comprising the attenuated SEA toxoid of claim 1 and a carrier.
19. The composition of claim 18 , further comprising an adjuvant.
20. The composition of claim 18 , further comprising an additional immunogen.
21. The composition of claim 20 , wherein the additional immunogen is a bacterial antigen selected from the group consisting of a pore forming toxin or a fragment thereof, a superantigen or a fragment thereof, a cell surface protein or a fragment thereof, and a combination of two or more of the bacterial antigens.
22. A composition comprising the multivalent oligopeptide of claim 5 and a carrier.
23. The composition of claim 22 , further comprising an adjuvant.
24. The composition of claim 22 , further comprising an additional immunogen.
25. The composition of claim 24 , wherein the additional immunogen is a bacterial antigen.
26. The composition of claim 25 , wherein the bacterial antigen is selected from the group consisting of a pore forming toxin or a fragment thereof, a superantigen or a fragment thereof, a cell surface protein or a fragment thereof, and a combination of two or more of the bacterial antigens.
27. A method of producing a vaccine against S. aureus infection, the method comprising isolating the attenuated SEA toxoid of claim 1 and combining the toxoid with an adjuvant.
28. A method of producing a vaccine against S. aureus infection, the method comprising isolating the multivalent oligopeptide of claim 5 and combining the oligopeptide with an adjuvant.
29. A method of inducing a host immune response against Staphylococcus aureus , comprising administering to a subject in need of the immune response an effective amount of the composition of claim 18 .
30. The method of claim 29 , wherein the composition is administered via intramuscular injection, intradermal injection, intraperitoneal injection, subcutaneous injection, intravenous injection, oral administration, mucosal administration, intranasal administration, or pulmonary administration.
31. A method of preventing or treating a Staphylococcal disease or infection in a subject comprising administering to a subject in need thereof the composition of claim 18 .
32. The method of claim 31 , wherein the infection is a localized or systemic infection of skin, soft tissue, blood, or an organ, or is auto-immune in nature.
33. The method of claim 31 , wherein the disease is a respiratory disease.
34. The method of claim 33 , wherein the respiratory disease is pneumonia.
35. The method of claim 31 , wherein the disease is sepsis.
36. The method of claim 35 , wherein the subject is a human.
37. A method of inducing a host immune response against Staphylococcus aureus , comprising administering to a subject in need of the immune response an effective amount of the composition of claim 22 .
38. A method of preventing or treating a Staphylococcal disease or infection in a subject comprising administering to a subject in need thereof the composition of claim 22 .
39. The method of claim 38 , wherein the infection is a localized or systemic infection of skin, soft tissue, blood, or an organ, or is auto-immune in nature.
40. The method of claim 38 , wherein the disease is a respiratory disease.
41. The method of claim 40 , wherein the respiratory disease is pneumonia.
42. The method of claim 38 , wherein the disease is sepsis.
43. The method of claim 38 , wherein the subject is a human.
44. The method of claim 38 , wherein the composition is administered via intramuscular injection, intradermal injection, intraperitoneal injection, subcutaneous injection, intravenous injection, oral administration, mucosal administration, intranasal administration, or pulmonary administration.