Compositions and methods related to protein A (SpA) variants
The present invention concerns methods and compositions for treating or preventing a bacterial infection, particularly infection by a Staphylococcus bacterium. The invention provides methods and compositions for stimulating an immune response against the bacteria. In certain embodiments, the methods and compositions involve a non-toxigenic Protein A (SpA) variant.
1. An isolated polypeptide comprising a variant Staphylococcus aureus Protein A (SpA) domain D segment having amino acid substitutions at amino acids corresponding to position 9, 10, 36 and 37 of SEQ ID NO: 2, wherein the substitutions at amino acids corresponding to positions 9 and 10 are with a glycine residue and the substitutions at amino acids corresponding to positions 36 and 37 are with a serine residue.
2. An pharmaceutical composition comprising the isolated polypeptide of claim 1 in a pharmaceutically acceptable formulation.
3. A method for eliciting an immune response against a Staphylococcus aureus bacterium in a subject comprising providing to the subject an effective amount of a composition comprising a variant Staphylococcus aureus Protein A (SpA) domain D segment having amino acid substitutions at amino acids corresponding to position 9, 10, 36 and 37 of SEQ ID NO: 2, wherein the substitutions at amino acids corresponding to positions 9 and 10 are with a glycine residue and the substitutions at amino acids corresponding to positions 36 and 37 are with a serine residue.
4. The method of claim 3 , where the subject is also administered an adjuvant.
5. The method of claim 3 , wherein the staphylococcus bacterium is a S. aureus bacterium.
6. The method of claim 3 , wherein the staphylococcus bacterium is resistant to one or more drug treatments.
7. The method of claim 6 , wherein the bacterium is methicillin resistant.
8. The method of claim 3 , wherein the composition is administered orally, parenterally, subcutaneously, intramuscularly, or intravenously.
9. The method of claim 3 , further comprising administering to the subject a composition comprising a second staphylococcal antigen.
10. The method of claim 3 , wherein the subject is human.
11. The method of claim 3 , wherein the immune response is a protective immune response.