COMPOSITIONS AND METHODS RELATED TO PROTEIN A (SpA) VARIANTS
AssigneeThe University of Chicago
InventorsOlaf SCHNEEWIND, Alice G. CHENG, Dominique M. MISSIAKAS, Hwan Keun Kim
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Abstract
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.
Claims77
An isolated polypeptide comprising a variant Protein A (SpA) having (a) at least one amino acid substitution that disrupts Fc binding and (b) at least a second amino acid substitution that disrupts VH3 binding and (c) an amino acid sequence that is at least 70% identical to the amino acid sequence of SEQ ID NO:2.
A peptide composition comprising, in a pharmaceutically acceptable composition, a non-toxigenic variant Protein A (SpA) peptide having one or more mutations that attenuate the binding of the Protein A domain D to IgG, Fcγ, VH3 F(ab)2, von Willebrand factor (vWF), and tumor necrosis factor α receptor 1 (TNFR1), wherein the composition is capable of stimulating an immune response in a subject in need thereof.
An immunogenic composition comprising an isolated peptide comprising a Protein A (SpA) variant having an amino acid substitution at amino acid positions 9, 10, 36, and 37 of SEQ ID NO:2.
A method for eliciting an immune response against a Staphylococcus bacterium in a subject comprising providing to the subject an effective amount of a composition comprising a Protein A (SpA) variant having an amino acid substitution at amino acid positions 9 and 10 of SEQ ID NO:2.
A method for treating a staphylococcal infection in a subject comprising providing to a subject having, suspected of having or at risk of developing a staphylococcal infection an effective amount of an isolated peptide comprising a Protein A variant having an amino acid substitution at amino acid positions 9 and 10 of SEQ ID NO:2.
Dependencies are inferred from the claim text.