Chimeric polypeptides

A chimeric or fusion protein for inducing an immune response to P. gingivalis, the protein comprising a first polypeptide and a second polypeptide, wherein:

• A) the first polypeptide comprises or consists of an amino acid sequence of the active site of an Arg- or Lys-gingipain of P. gingivalis, or a sequence that is at least 80% identical thereto;
• and
• B) the second polypeptide comprises or consists of an amino acid sequence of an adhesin domain of an Arg- or Lys-gingipain of P. gingivalis;
• wherein the second polypeptide comprises the sequence of one or more adhesin binding motifs (ABMs), and
• wherein the second polypeptide comprises part or all of the sequence of a cleaved adhesin domain (CAD), and wherein the second polypeptide:
• a) comprises an amino acid sequence corresponding substantially to the full length of the DUF2436 domain of an Arg- or Lys-gingipain, or a sequence at least 80% identical thereto;
• b) comprises one or more cysteine amino acid substitutions in the adhesin domain, compared to the naturally occurring Arg- or Lys-gingipain sequences in corresponding regions;
• and
• c) comprises one or more amino acid motif substitutions selected from:
• i) substitution of the proline and/or an asparagine residues in the sequence PxxN corresponding to, or at a position equivalent to, residues 6 to 9 of the sequence of SEQ ID NO:
• 14 or 19 (ABM1);
• ii) substitution of the motif NxFA to SxYQ in the sequence, corresponding to, or at a position equivalent to residues 2 to 5 of the sequence of SEQ ID NO:
• 14 or 19 (ABM1);
• iii) substitution of the second tyrosine residue, corresponding to or at a position equivalent to residues at position 5 of SEQ ID NO:
• 15 or 20 (ABM2), and of the tryptophan residue, corresponding to or at a position equivalent to residue at position 23 of SEQ ID NO:
• 14 or 19 (ABM1) to alanine residues.