POLYPEPTIDES FOR INDUCING A PROTECTIVE IMMUNE RESPONSE AGAINST STAPHYLOCOCCUS AUREUS
The present invention features polypeptides comprising an amino acid sequence structurally related to SEQ ID NO: 1 and uses of such polypeptides and compositions thereof. SEQ ID NO: 1 is a full length S. aureus sequence. A derivative of SEQ ID NO: 1 containing an amino terminus his-tag was found to produce a protective immune response against S. aureus.
1 . A polypeptide comprising an amino acid sequence with up to 8 amino acid alterations from the amino acid sequence as set forth in SEQ ID NO: 1, wherein said polypeptide is not SEQ ID NO: 1 or SEQ ID NO: 6, and wherein said polypeptide provides protective immunity against S. aureus.
2 . The polypeptide of claim 1 , wherein said polypeptide comprises a portion of SEQ ID NO: 1 selected from the group consisting of: amino acids 5-60, amino acids 9-64, amino acids 1-56, amino acids 4-59, amino acids 8-63, amino acids 2-57, amino acids 3-58, amino acids 7-62, and amino acids 6-61.
3 . The polypeptide of claim 1 , wherein said polypeptide is substantially purified.
4 . The polypeptide of claim 3 , wherein said polypeptide provides protective immunity against an S. aureus strain that expresses SEQ ID NO: 1.
5 . An immunogen comprising a polypeptide consisting of an amino acid sequence with up to 8 amino acid alterations from SEQ ID NO: 1 and one or more additional regions or moieties covalently joined to said amino acid sequence, wherein each region or moiety is independently selected from a region or moiety having at least one of the following properties: enhances the immune response, facilitates purification, or facilitates polypeptide stability.
6 . The immunogen of claim 5 , wherein said polypeptide provides protective immunity against an S. aureus strain that expresses SEQ ID NO: 1.
7 . A composition able to induce a protective immune response in a patient against S. aureus infection comprising an immunologically effective amount of
the polypeptide of claim 4 ,
and a pharmaceutically acceptable carrier.
8 . A composition able to induce a protective immune response in a patient against S. aureus infection comprising an immunologically effective amount of a polypeptide comprising an amino acid sequence with up to 8 amino acid alterations from the amino acid sequence as set forth in SEQ ID NO: 1, wherein said polypeptide does not consist of the amino acid sequence as set forth in SEQ ID NO: 1, and pharmaceutically acceptable carrier.
9 . The composition of claim 8 , wherein said composition provides protective immunity against a S. aureus strain that expresses SEQ ID NO: 1.
10 . The composition of claim 8 , wherein said composition further comprises an adjuvant.
11 . A nucleic acid molecule comprising a recombinant gene which comprises a nucleotide sequence encoding the polypeptide of claim 1 .
12 . The nucleic acid molecule of claim 11 , wherein said nucleic acid molecule is an expression vector.
13 . A recombinant cell comprising a recombinant gene which comprises a nucleotide sequence encoding the polypeptide of claim 1 .
14 . A method of making a polypeptide immunogen comprising the steps of:
(a) growing the recombinant cell of claim 13 under conditions wherein said polypeptide is expressed; and,
(b) purifying said polypeptide.
15 . A method of inducing a protective immune response in a patient against a S. aureus infection comprising the step of administering to said patient an immunologically effective amount of one or more of the following:
(a) the polypeptide of claim 1 ;
(b) a polypeptide having the amino acid sequence as set forth in SEQ ID NO: 1; or
(c) a polypeptide having the amino acid sequence as set forth in SEQ ID NO: 6.
16 . The method of claim 15 , wherein said patient is a human.
17 - 19 . (canceled)
20 . A composition able to induce a protective immune response in a patient against S. aureus infection comprising an immunologically effective amount of the immunogen of claim 5 .
21 . A method of inducing a protective immune response in a patient against a S. aureus infection comprising the step of administering to said patient an immunologically effective amount of the immunogen of claim 5 .
22 . A method of inducing a protective immune response in a patient against a S. aureus infection comprising the step of administering to said patient an immunologically effective amount of the composition of claim 7 .