Staphylococcal protein variants and truncates

A vaccine composition comprising a selection of polypeptides, which includes:

• a) an Alpha-hemolysin (Hla) polypeptide or a variant thereof, where said variant preferably exhibits reduced or no hemolytic activity and/or which preferably can induce antibodies that block the hemolytic activity of native Hla, wherein said polypeptide is an immunogenic polypeptide consisting of or comprising a variant of the amino acid sequence of Hla, which variant:
• i. has at least 85% sequence identity with the sequence of SEQ ID NO:
• 2, and
• ii. comprises one or more amino acid deletion(s) and/or substitution(s) in the first 12 consecutive N-terminal amino acid residues of the amino acid sequence of mature Hla, said first 12 consecutive N-terminal amino acid residues corresponding to positions 1 to 12 of SEQ ID NO:
• 2,
• wherein the polypeptide is unable to participate in formation of a heptameric structure with other Hla molecules and wherein any substitution(s) in ii) are preferably non-conservative, and at least one of b-d:
• b) a LukE polypeptide or a variant thereof, where said variant preferably exhibits reduced or no leukocytic activity and/or which preferably can induce antibodies that block the leukocytic activity of native LukE,
• c) an Immunoglobulin G-binding protein A (SpA) polypeptide or a variant thereof, where said variant preferably exhibits a reduced ability to bind human IgG and human von Willebrandt Factor and/or which preferably can induce antibodies that block native SpA interaction with human IgG, and
• d) an Aureolysin (Aur) polypeptide or a variant thereof, where said variant preferably exhibits reduced catalytic activity and which preferably can induce antibodies that block the catalytic activity of native Aur,
• said composition optionally further comprising a pharmaceutically acceptable carrier, vehicle or diluent, and further optionally an immunogenic adjuvant, which is in particular selected from AIOH, SLA-SE and OMVs (outer membrane vesicles).