Immunogenic compositions of
View Patent ↗The present invention relates to immunogenic compositions, comprising polypeptides and polysaccharides from Staphylococcus aureus . The present invention also relates to immunogenic compositions, comprising Staphylococcus aureus capsule polysaccharides conjugated to a carrier protein. In addition, the invention relates to methods of inducing an immune response in subjects against Staphylococcus aureus using immunogenic compositions of the Staphylococcus aureus polypeptides and capsule polysaccharides.
1. An immunogenic composition comprising an isolated Staphylococcus aureus clumping factor A (ClfA) polypeptide, an isolated S. aureus manganese transporter protein C (MntC protein), an isolated S. aureus capsular polysaccharide type 5 conjugated to CRM 197 , and an isolated S. aureus capsular polysaccharide type 8 conjugated to CRM 197 , wherein the capsular polysaccharide type 5 has a molecular weight of between 70 and 300 kDa and the capsular polysaccharide type 8 has a molecular weight of between 70 and 150 kDa.
2. The immunogenic composition of claim 1 , wherein the ClfA polypeptide is a polypeptide fragment comprising (a) a fibrinogen binding domain; (b) N1, N2, and N3 domains; or (c) N2 and N3 domains of ClfA.
3. The immunogenic composition according to claim 1 , wherein the ClfA polypeptide is a mutated ClfA polypeptide.
4. The immunogenic composition of claim 3 , wherein the mutated ClfA polypeptide has an amino acid substitution at one or more of Tyr 338, Tyr 256, Pro 336, Lys 389, Ala 254 and Ile 387 in SEQ ID NO:130.
5. The immunogenic composition of claim 4 , wherein the amino acid substitution at one or more of Tyr 338, Tyr 256, Pro 336, Lys 389, Ala 254 and Ile 387 is to Ala or Ser.
6. The immunogenic composition of claim 5 , wherein the Tyr 338 is substituted to Ala.
7. The immunogenic composition of claim 1 , wherein the capsular polysaccharide type 5 has a molecular weight of between 70 and 150 kDa.
8. The immunogenic composition of claim 1 , wherein the capsular polysaccharide type 5 is between 10% and 100% O acetylated, between 50 and 100% O acetylated, or between 75% and 100% O acetylated.
9. The immunogenic composition of claim 1 , wherein the capsular polysaccharide type 8 is between 10% and 100% O acetylated, between 50 and 100% O acetylated, or between 75% and 100% O acetylated.
10. The immunogenic composition of claim 1 , wherein the S. aureus MntC protein is a lipidated or a non-lipidated protein.
11. An immunogenic composition comprising an isolated Staphylococcus aureus manganese transporter protein C (MntC protein), an isolated S. aureus capsular polysaccharide type 5 conjugated to CRM 197 , and an isolated S. aureus capsular polysaccharide type 8 conjugated to CRM 197 , wherein the capsular polysaccharide type 5 has a molecular weight of between 70 and 300 kDa and the capsular polysaccharide type 8 has a molecular weight of between 70 and 150 kDa.
12. The immunogenic composition of claim 1 , further comprising an adjuvant.
13. The immunogenic composition of claim 1 , further comprising a pharmaceutically acceptable carrier.
14. The immunogenic composition of claim 1 , further comprising an antigen selected from the group consisting of Opp3a, DItD, HtsA, LtaS, IsdA, IsdB IsdC, SdrC, SdrD, SdrE, SdrF, SdrG, SdrH, SrtA, SpA, Sbi, FmtB, alpha-hemolysin (hla), beta-hemolysin, fibronectin-binding protein A (fnbA), fibronectin-binding protein B (fnbB), coagulase, Fig, map, Panton-Valentine leukocidin (pvl), alpha-toxin and its variants, gamma toxin (hlg) and variants, ica, immunodominant ABC transporter, Mg2+ transporter, Ni ABC transporter, RAP, autolysin, laminin receptors, IsaA/PisA, IsaB/PisB, SPOIIIE, SsaA, EbpS, Sas A, SasF, SasH, EFB (FIB), SBI, Npase, EBP, bone sialo binding protein II, aureolysin precursor (AUR)/Sepp1, CNA, and fragments thereof such as M55, TSST-1, mecA, poly-N-acetylglucosamine (PNAG/dPNAG) exopolysaccharide, GehD, EbhA, EbhB, SSP-1, SSP-2, HBP, vitronectin binding protein, HarA, EsxA, EsxB, Enterotoxin A, Enterotoxin B, Enterotoxin C1, and novel autolysin.
15. A method of inducing an immune response against Staphylococcus aureus comprising administering to a subject an immunologically effective amount of the immunogenic composition of claim 1 .
16. The method of claim 15 , wherein the immune response reduces a disease associated with a staphylococcal organism in a subject.
17. The method of claim 16 , wherein the disease is selected from the group consisting of invasive S. aureus disease, sepsis, and carriage.
18. The method of claim 15 , wherein the immune response induced comprises the generation of antibodies having opsonophagocytic activity (OPA) against S. aureus.