Immunogenic composition comprising staphylococcal antigens

1. An immunogenic composition comprising

a. a clumping factor A (ClfA) antigen comprising an amino acid sequence at least 95% identical to SEQ ID NO: 32, wherein the ClfA antigen comprises a serine at a position equivalent to P116 of SEQ ID NO: 2; an alanine at a position equivalent to Y118 of SEQ ID NO: 2, and the sequence KDQNATK (SEQ ID NO: 31) beginning at a position equivalent to I337 of SEQ ID NO: 2;

b. an alpha-haemolysin (Hla) antigen comprising an amino acid sequence at least 95% identical to SEQ ID NO: 12, wherein the Hla antigen comprises a leucine at a position equivalent to H35 of SEQ ID NO: 3, a cysteine at a position equivalent to H48 of SEQ ID NO: 3, a cysteine at a position equivalent to G122 of SEQ ID NO: 3, and the sequence KDQNRTK (SEQ ID NO: 30) beginning at a position equivalent to K131 of SEQ ID NO: 3; and

c. a Staphylococcal protein A (SpA) antigen comprising an amino acid sequence at least 95% identical to SEQ ID NO: 27, wherein the SpA antigen comprises a lysine at positions equivalent to positions Q43, Q44, Q96, Q104, Q105, Q162, Q163, Q220, Q221, Q278, and Q279 of SEQ ID NO: 4; an arginine at a position equivalent to position Q97 of SEQ ID NO: 4; and an alanine at positions equivalent to positions D70, D71, D131, D132, D189, D190, D247, D248, D305, and D306;

wherein the ClfA antigen is conjugated to a Staphylococcus aureus serotype 8 capsular polysaccharide, and the Hla antigen is conjugated to a S. aureus serotype 5 capsular polysaccharide.

2. The immunogenic composition according to claim 1 , wherein

a. the amino acid sequence of part (a) is at least 96%, 97%, 98% or 99% identical to SEQ ID NO. 32;

b. the amino acid sequence of part (b) is at least 96%, 97%, 98% or 99% identical to SEQ ID NO. 12; and/or

c. the amino acid sequence of part (c) is at least 96%, 97%, 98% or 99% identical to SEQ ID NO. 27.

3. The immunogenic composition according to claim 2 , wherein the ClfA antigen comprises or consists of the sequence of SEQ ID NO: 7 or SEQ ID NO: 32.

4. The immunogenic composition according to claim 2 , wherein the Hla antigen comprises or consists of the sequence of SEQ ID NO: 11 or SEQ ID NO: 12.

5. The immunogenic composition according to claim 2 , wherein the SpA antigen comprises or consists of the sequence of SEQ ID NO: 26 or SEQ ID NO: 27.

6. The immunogenic composition according to claim 2 , wherein (i) the ClfA antigen comprises the amino acid sequence of SEQ ID NO: 7 or SEQ ID NO: 32; (ii) the Hla antigen comprises the amino acid sequence of SEQ ID NO: 11 or SEQ ID NO: 12; and (iii) the SpA antigen comprises the amino acid sequence of SEQ ID NO: 26 or SEQ ID NO: 27.

7. The immunogenic composition according to claim 1 , wherein said ClfA-CP8 and Hla-CP5 conjugates are bioconjugates.

8. The immunogenic composition according to claim 2 , further comprising an adjuvant.

9. A kit comprising (i) a first container comprising the immunogenic composition of claim 2 ; and (ii) a second container comprising an adjuvant.

10. The immunogenic composition of claim 8 , wherein the adjuvant comprises a saponin and a Toll Like Receptor 4 (TLR4) agonist.

11. The immunogenic composition of claim 10 , wherein the TLR4 agonist is a lipopolysaccharide.

12. The immunogenic composition of claim 11 , wherein the lipopolysaccharide is 3-de-O-acylated monophosphoryl lipid A (3D-MPL).

13. The immunogenic composition of claim 10 , wherein the saponin comprises an active fraction of the saponin derived from the bark of Quillaja Saponaria Molina.

14. The immunogenic composition of claim 13 , wherein the active fraction of the saponin derived from the bark of Quillaja Saponaria Molina is QS21.

15. The immunogenic composition of claim 8 , wherein the adjuvant comprises 3D-MPL and QS21 in a liposome.

16. The immunogenic composition of claim 8 , wherein the adjuvant comprises a Toll Like Receptor 7 (TLR7) agonist adsorbed to aluminum hydroxide (AlOH).