Immunogenic composition comprising staphylococcal antigens

Abstract

The invention provides an immunogenic composition comprising staphylococcal antigens, containing protein antigens and conjugates of capsular polysaccharides. Adjuvanted formulations are also provided. The invention may find use in the prevention and treatment of staphylococcal infections.

1 - 47 . (canceled) 
     
     
         48 . A method of prevention or treatment of staphylococcal infection, comprising administering to a subject in need thereof 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 1337 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 ositions 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 type 8 capsular polysaccharide, and the Hla antigen is conjugated to a  S. aureus  serotype 5 capsular polysaccharide.   
     
     
         49 - 53 . (canceled) 
     
     
         54 . The method according to  claim 48 , 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.   
     
     
         55 . The method according to  claim 54 , wherein the ClfA antigen comprises or consists of the sequence of SEQ ID NO: 7 or SEQ ID NO: 32. 
     
     
         56 . The method according to  claim 54 , wherein the Hla antigen comprises or consists of the sequence of SEQ ID NO: 11 or SEQ ID NO: 12. 
     
     
         57 . The method according to  claim 54 , wherein the SpA antigen comprises or consists of the sequence of SEQ ID NO: 26 or SEQ ID NO: 27. 
     
     
         58 . The method according to  claim 54 , 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. 
     
     
         59 . The method according to  claim 48 , wherein said ClfA-CP8 and Hla-CP5 conjugates are bioconjugates. 
     
     
         60 . The method according to  claim 48 , the immunogenic composition further comprising an adjuvant. 
     
     
         61 . The method of  claim 60 , wherein the adjuvant comprises a saponin and a Toll Like Receptor 4 (TLR4) agonist. 
     
     
         62 . The method according to  claim 61 , wherein the TLR4 agonist is a lipopolysaccharide. 
     
     
         63 . The method according to  claim 62 , wherein the lipopolysaccharide is 3-de-O-acylated monophosphoryl lipid A (3D-MPL). 
     
     
         64 . The method according to  claim 61 , wherein the saponin comprises an active fraction of the saponin derived from the bark of  Quillaja Saponaria Molina.    
     
     
         65 . The method according to  claim 64 , wherein the active fraction of the saponin derived from the bark of  Quillaja Saponaria Molina  is QS21. 
     
     
         66 . The method according to  claim 60 , wherein the adjuvant comprises 3D-ML and QS21 in a liposome. 
     
     
         67 . The method according to  claim 60 , wherein the adjuvant comprises a Toll Like Receptor 7 (TLR7) agonist adsorbed to aluminum hydroxide (AlOH). 
     
     
         68 . The method of  claim 66 , wherein the adjuvant comprises 3D-MPL at a level of 25 μg per human dose and QS21 at a level of 25 μg per human dose. 
     
     
         69 . The method of  claim 60 , wherein said adjuvant is administered concomitantly with the immunogenic composition. 
     
     
         70 . The method according to  claim 60 , wherein the adjuvant is mixed with the immunogenic composition before administering to the subject. 
     
     
         71 . The method of  claim 69 , wherein the adjuvant comprises a saponin and a TLR4 agonist. 
     
     
         72 . The method of  claim 69 , wherein the adjuvant comprises 3D-MPL and QS21 in a liposome.