Multivalent vaccine protection from
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.
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.