Multivalent vaccine protection from Staphylococcus aureus infection

Abstract

Vaccine formulations effective against Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus (MRSA) are disclosed, as well as methods of using the vaccine formulations in the treatment and prevention of Staphylococcus aureus infections in a subject.

What is claimed is: 
     
       1. An immunogenic composition comprising:
 (a) five purified Staphylococcus aureus polypeptides, or portions thereof, or variants thereof, or combinations thereof, wherein the S. aureus polypeptides are (i) biofilm-specific S. aureus polypeptide SA0037 set forth in SEQ ID NO: 13, (ii) planktonic-specific S. aureus polypeptide SA0119 set forth in SEQ ID NO: 14, (iii) biofilm-specific S. aureus polypeptide SA0486 set forth in SEQ ID NO: 15, (iv) biofilm-specific S. aureus polypeptide SA0688 set forth in SEQ ID NO:16, and (v) biofilm-specific S. aureus glucosaminidase set forth in SEQ ID NO: 17, wherein each of the portions is at least 95% of the size of the corresponding full-length polypeptide, and wherein each of the variants has at least 95% sequence identity with the corresponding full-length polypeptide, 
 (b) a pharmaceutically acceptable carrier or diluent and 
 (c) an immunostimulatory amount of an adjuvant. 
 
     
     
       2. The composition of  claim 1 , wherein the five purified S. aureus polypeptides are full-length S. aureus polypeptides. 
     
     
       3. A formulation comprising an immunologically effective amount of a vaccine comprising:
 (a) five purified Staphylococcus aureus polypeptides, wherein the S. aureus polypeptides are (i) biofilm-specific S. aureus polypeptide SA0037 set forth in SEQ ID NO: 13, (ii) planktonic-specific S. aureus polypeptide SA0119 set forth in SEQ ID NO: 14, (iii) biofilm-specific S. aureus polypeptide SA0486 set forth in SEQ ID NO: 15, (iv) biofilm-specific S. aureus polypeptide SA0688 set forth in SEQ ID NO:16, and (v) biofilm-specific S. aureus glucosaminidase set forth in SEQ ID NO: 17, 
 (b) a pharmaceutically acceptable carrier or diluent and 
 (c) an immunostimulatory amount of an adjuvant. 
 
     
     
       4. A formulation comprising an immunologically effective amount of a vaccine consisting of:
 (a) five purified Staphylococcus aureus polypeptides, wherein the S. aureus polypeptides are (i) biofilm-specific S. aureus polypeptide SA0037 set forth in SEQ ID NO: 13, (ii) planktonic-specific S. aureus polypeptide SA0119 set forth in SEQ ID NO: 14, (iii) biofilm-specific S. aureus polypeptide SA0486 set forth in SEQ ID NO: 15, (iv) biofilm-specific S. aureus polypeptide SA0688 set forth in SEQ ID NO:16, and (v) biofilm-specific S. aureus glucosaminidase set forth in SEQ ID NO: 17, 
 (b) a pharmaceutically acceptable carrier or diluent and 
 (c) an immunostimulatory amount of an adjuvant. 
 
     
     
       5. A method of generating an immune response against S. aureus in a subject comprising administering to the subject an immunologically effective amount of the formulation of  claim 3 . 
     
     
       6. A method of generating an immune response against S. aureus in a subject comprising administering to the subject an immunologically effective amount of the formulation of  claim 4 . 
     
     
       7. A formulation comprising an immunologically effective amount of a pentavalent vaccine consisting of:
 (a) five purified Staphylococcus aureus polypeptides, wherein the S. aureus polypeptides are (i) biofilm-specific S. aureus polypeptide SA0037 set forth in SEQ ID NO: 13, (ii) planktonic-specific S. aureus polypeptide SA0119 set forth in SEQ ID NO: 14, (iii) biofilm-specific S. aureus polypeptide SA0486 set forth in SEQ ID NO: 15, (iv) biofilm-specific S. aureus polypeptide SA0688 set forth in SEQ ID NO:16, and (v) biofilm-specific S. aureus glucosaminidase set forth in SEQ ID NO: 17, and 
 (b) a pharmaceutically acceptable carrier or diluent, wherein the vaccine elicits complete protection against a biofilm-associated S. aureus implant infection in a mammal with 100% clearance of the infecting S. aureus. 
 
     
     
       8. A method of eliciting a protective immune response against a biofilm-associated S. aureus implant infection in a mammal comprising administering to the mammal an immunologically effective amount of the formulation of  claim 7 . 
     
     
       9. An immunogenic composition comprising:
 (a) five purified Staphylococcus aureus polypeptides, or variants thereof, or combinations thereof, wherein the S. aureus polypeptides are:   (i) a portion of biofilm-specific S. aureus polypeptide SA0037 set forth in SEQ ID NO: 13, wherein the portion is at least 90% of the size of the polypeptide set forth in SEQ ID NO: 13,   (ii) a portion of planktonic-specific S. aureus polypeptide SA0119 set forth in SEQ ID NO: 14, wherein the portion is at least 65% of the size of the polypeptide set forth in SEQ ID NO: 14,   (iii) a portion of biofilm-specific S. aureus polypeptide SA0486 set forth in SEQ ID NO: 37, wherein the portion is at least 85% of the size of the polypeptide set forth in SEQ ID NO: 37,   (iv) a portion of biofilm-specific S. aureus polypeptide SA0688 set forth in SEQ ID NO:38, wherein the portion is at least 95% of the size of the polypeptide set forth in SEQ ID NO: 38, and   (v) a portion of biofilm-specific S. aureus glucosaminidase set forth in SEQ ID NO: 39, wherein the portion is at least 95% of the size of the polypeptide set forth in SEQ ID NO: 39,   wherein each variant has at least 95% sequence identity with the corresponding S. aureus polypeptide;   (b) a pharmaceutically acceptable carrier or diluent; and   (c) an immunostimulatory amount of an adjuvant.   
     
     
       10. A formulation comprising an immunologically effective amount of a vaccine comprising of:
 (a) five purified Staphylococcus aureus polypeptides, or variants thereof, or combinations thereof, wherein the S. aureus polypeptides are:   (i) a portion of biofilm-specific S. aureus polypeptide SA0037 set forth in SEQ ID NO: 13, wherein the portion is at least 90% of the size of the polypeptide set forth in SEQ ID NO: 13,   (ii) a portion of planktonic-specific S. aureus polypeptide SA0119 set forth in SEQ ID NO: 14, wherein the portion is at least 65% of the size of the polypeptide set forth in SEQ ID NO: 14,   (iii) a portion of biofilm-specific S. aureus polypeptide SA0486 set forth in SEQ ID NO: 37, wherein the portion is at least 85% of the size of the polypeptide set forth in SEQ ID NO: 37,   (iv) a portion of biofilm-specific S. aureus polypeptide SA0688 set forth in SEQ ID NO:38, wherein the portion is at least 95% of the size of the polypeptide set forth in SEQ ID NO: 38, and   (v) a portion of biofilm-specific S. aureus glucosaminidase set forth in SEQ ID NO: 39, wherein the portion is at least 95% of the size of the polypeptide set forth in SEQ ID NO: 39,   wherein each variant has at least 95% sequence identity with the corresponding S. aureus polypeptide,   (b) a pharmaceutically acceptable carrier or diluent; and   (c) an immunostimulatory amount of an adjuvant.   
     
     
       11. A method of generating an immune response against S. aureus in a subject comprising administering to the subject an immunologically effective amount of the formulation of claim 10. 
     
     
       12. A formulation comprising an immunologically effective amount of a pentavalent vaccine consisting of:
 (a) five purified Staphylococcus aureus polypeptides, or variants thereof, or combinations thereof, wherein the S. aureus polypeptides are:   (i) a portion of biofilm-specific S. aureus polypeptide SA0037 set forth in SEQ ID NO: 13, wherein the portion is at least 90% of the size of the polypeptide set forth in SEQ ID NO: 13,   (ii) a portion of planktonic-specific S. aureus polypeptide SA0119 set forth in SEQ ID NO: 14, wherein the portion is at least 65% of the size of the polypeptide set forth in SEQ ID NO: 14,   (iii) a portion of biofilm-specific S. aureus polypeptide SA0486 set forth in SEQ ID NO: 37, wherein the portion is at least 85% of the size of the polypeptide set forth in SEQ ID NO: 37,   (iv) a portion of biofilm-specific S. aureus polypeptide SA0688 set forth in SEQ ID NO:38, wherein the portion is at least 95% of the size of the polypeptide set forth in SEQ ID NO: 38, and   (v) a portion of biofilm-specific S. aureus glucosaminidase set forth in SEQ ID NO: 39, wherein the portion is at least 95% of the size of the polypeptide set forth in SEQ ID NO: 39,   wherein each variant has at least 95% sequence identity with the corresponding S. aureus polypeptide; and   (b) a pharmaceutically acceptable carrier or diluent;   wherein the vaccine elicits complete protection against a biofilm-associated S. aureus implant infection in a mammal with 100% clearance of the infecting S. aureus.   
     
     
       13. A method of eliciting a protective immune response against a biofilm-associated S. aureus implant infection in a mammal comprising administering to the mammal an immunologically effective amount of the formulation of claim 12. 
     
     
       14. An immunogenic composition comprising:
 (a) five purified Staphylococcus aureus polypeptides, wherein the S. aureus polypeptides are:   (i) a portion of biofilm-specific S. aureus polypeptide SA0037 set forth in SEQ ID NO: 13, wherein the portion is at least 90% of the size of the polypeptide set forth in SEQ ID NO: 13,   (ii) a portion of planktonic-specific S. aureus polypeptide SA0119 set forth in SEQ ID NO: 14, wherein the portion is at least 65% of the size of the polypeptide set forth in SEQ ID NO: 14,   (iii) a portion of biofilm-specific S. aureus polypeptide SA0486 set forth in SEQ ID NO: 37, wherein the portion is at least 85% of the size of the polypeptide set forth in SEQ ID NO: 37,   (iv) a portion of biofilm-specific S. aureus polypeptide SA0688 set forth in SEQ ID NO:38, wherein the portion is at least 95% of the size of the polypeptide set forth in SEQ ID NO: 38, and   (v) a portion of biofilm-specific S. aureus glucosaminidase set forth in SEQ ID NO: 39, wherein the portion is at least 95% of the size of the polypeptide set forth in SEQ ID NO: 39;   (b) a pharmaceutically acceptable carrier or diluent; and   (c) an immunostimulatory amount of an adjuvant.   
     
     
       15. A formulation comprising an immunologically effective amount of a vaccine comprising of:
 (a) five purified Staphylococcus aureus polypeptides, wherein the S. aureus polypeptides are:   (i) a portion of biofilm-specific S. aureus polypeptide SA0037 set forth in SEQ ID NO: 13, wherein the portion is at least 90% of the size of the polypeptide set forth in SEQ ID NO: 13,   (ii) a portion of planktonic-specific S. aureus polypeptide SA0119 set forth in SEQ ID NO: 14, wherein the portion is at least 65% of the size of the polypeptide set forth in SEQ ID NO: 14,   (iii) a portion of biofilm-specific S. aureus polypeptide SA0486 set forth in SEQ ID NO: 37, wherein the portion is at least 85% of the size of the polypeptide set forth in SEQ ID NO: 37,   (iv) a portion of biofilm-specific S. aureus polypeptide SA0688 set forth in SEQ ID NO:38, wherein the portion is at least 95% of the size of the polypeptide set forth in SEQ ID NO: 38, and   (v) a portion of biofilm-specific S. aureus glucosaminidase set forth in SEQ ID NO: 39, wherein the portion is at least 95% of the size of the polypeptide set forth in SEQ ID NO: 39;   (b) a pharmaceutically acceptable carrier or diluent; and   (c) an immunostimulatory amount of an adjuvant.   
     
     
       16. A method of generating an immune response against S. aureus in a subject comprising administering to the subject an immunologically effective amount of the formulation of claim 15. 
     
     
       17. A formulation comprising an immunologically effective amount of a pentavalent vaccine consisting of:
 (a) five purified Staphylococcus aureus polypeptides, wherein the S. aureus polypeptides are:   (i) a portion of biofilm-specific S. aureus polypeptide SA0037 set forth in SEQ ID NO: 13, wherein the portion is at least 90% of the size of the polypeptide set forth in SEQ ID NO: 13,   (ii) a portion of planktonic-specific S. aureus polypeptide SA0119 set forth in SEQ ID NO: 14, wherein the portion is at least 65% of the size of the polypeptide set forth in SEQ ID NO: 14,   (iii) a portion of biofilm-specific S. aureus polypeptide SA0486 set forth in SEQ ID NO: 37, wherein the portion is at least 85% of the size of the polypeptide set forth in SEQ ID NO: 37,   (iv) a portion of biofilm-specific S. aureus polypeptide SA0688 set forth in SEQ ID NO:38, wherein the portion is at least 95% of the size of the polypeptide set forth in SEQ ID NO: 38, and   (v) a portion of biofilm-specific S. aureus glucosaminidase set forth in SEQ ID NO: 39, wherein the portion is at least 95% of the size of the polypeptide set forth in SEQ ID NO: 39; and   (b) a pharmaceutically acceptable carrier or diluent;   wherein the vaccine elicits complete protection against a biofilm-associated S. aureus implant infection in a mammal with 100% clearance of the infecting S. aureus.   
     
     
       18. A method of eliciting a protective immune response against a biofilm-associated S. aureus implant infection in a mammal comprising administering to the mammal an immunologically effective amount of the formulation of claim 17.