Methods and compositions comprising staphylococcus protein a (spa) variants

An isolated polypeptide comprising a variant Protein A (SpA) having (i) lysine substitutions for glutamine residues in each of domains A-E corresponding to positions 9 and 10 in domain D and (ii) threonine substitutions in each of domains A-E corresponding to position 33 in domain D, wherein the polypeptide does not, relative to a negative control, detectably crosslink IgG and IgE in blood or activate basophils or mast cells.

The isolated polypeptide of claim 1, wherein the KA binding affinity for variable heavy 3 (VH3) from human IgG is reduced as compared to a SpA variant consisting of lysine substitutions for glutamine residues in each of domains A-E corresponding to position 9 and 10 in domain D and alanine substitutions for aspartic acid in domains A-E corresponding to position 36 and 37 of domain D (SpAKKAA).

The isolated polypeptide of claim 1, wherein the isolated polypeptide has a KA binding affinity for VH3 from human IgG that is reduced by at least 2-fold as compared to SpAKKAA.

The isolated polypeptide of claim 1, wherein the isolated polypeptide has a KA binding affinity for VH3 from human IgG that is less than 1×105 M−1.

The isolated polypeptide of claim 1, wherein the SpA variant does not have substitutions in any of the domains A-E corresponding to positions 36 and 37 in domain D.

The isolated polypeptide of claim 1, wherein the only substitutions in the SpA variant are (i) and (ii).

The isolated polypeptide of claim 1, wherein the isolated polypeptide consists of the SpA variant.

A composition comprising the isolated polypeptide of claim 1, wherein the composition contains less than 1% by weight of the total protein amount a protein other than the isolated polypeptide.

A method for eliciting a safe immune response against a Staphylococcus bacteria in a human patient comprising administering to the human patient an effective amount of the composition of claim 8.

The method of claim 9, wherein the Staphylococcus bacteria comprises the WU1 or JSNZ strain of Staphylococcus aureus.

The method of claim 9, wherein the Staphylococcus bacteria comprises type ST88 isolate or any other human Staphylococcus bacterium now adapted to an animal.

The method of claim 9, wherein the human patient is a pediatric patient.

The method of claim 12, wherein the pediatric patient is 2 years old or less.

The method of claim 9, wherein the human patient is 65 years old or older.

The method of claim 9, wherein the human patient is a health care worker.

The method of claim 9, wherein the isolated polypeptide or composition is administered in four doses and wherein the interval between doses is at least four weeks.

An isolated polypeptide comprising a variant Protein A (SpA) having (i) lysine substitutions for glutamine residues corresponding to positions 9 and 10 in each of domains A-E and (ii) at least one other amino acid substitution corresponding to position 29 and/or 33 in SEQ ID NO:

• 2 in each of domains A-E, wherein the SpA variant has a KD binding affinity for VH3 from human IgG that is greater than 1.0×10−4 M and/or a KD binding affinity for VH3 from human IgE that is greater than 1.0×10−6 M.

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 the isolated polypeptide of claim 1.

A method for decolonization or for preventing colonization or recolonization of Staphylococcus bacteria in a subject comprising administering to the subject an effective amount of the isolated polypeptide of claim 1.