Method of prophlactically treating infection using a recombinant fibrinogen binding protein clumping factor A (ClfA) or fragment thereof

Patent metadata

Field	Value
Publication number	US-9353160-B2
Application number	US-201013384234-A
Country	US
Kind code	B2
Filing date	Jul 16, 2010
Priority date	Jul 16, 2009
Publication date	May 31, 2016
Grant date	May 31, 2016

Abstract

The present invention is directed to improved microbial antigen vaccines, pharmaceutical compositions, immunogenic compositions and antibodies and their use in the treatment of microbial infections, particularly those of bacterial origin, including Staphylococcal origin. Ideally, the present invention is directed to a recombinant staphylococcal MSCRAMM or MSCRAMM-like proteins, or fragment thereof, with reduced binding to its host ligand, for use in therapy.

First claim

The invention claimed is:

1. A method of inducing an immune response in a patient, the method comprising administering to the patient a recombinant fibrinogen binding protein clumping factor A (ClfA) according to:
(a) SEQ ID No. 20, wherein X 336 is serine or alanine and X 338 is serine or alanine;
(b) a sequence with 85% sequence identity to the sequence of SEQ ID No. 20 provided that D 321 is substituted with tyrosine, P 336 is substituted with serine or alanine, and Y 338 is substituted with serine or alanine, or
(c) a fragment of (a) or (b) comprising at least amino acid residues 221 to 531 of a fibrinogen binding region (Region A),
(d) subregion N123, spanning amino acid residues 40 to 559 of SEQ ID NO:20 wherein X 336 is serine or alanine and X 338 is serine or alanine; or
(e) subregion N23, spanning amino acid residues 221 to 559 of SEQ ID NQ:20 wherein X 336 is serine or alanine and X 338 is serine or alanine,
such that the recombinant protein has reduced ability or lacks the ability to non-covalently bind fibrinogen compared to the non-mutated protein or fragment thereof, stimulates a greater immune response than the wild type ClfA protein, and has increased stability compared to rClfAP 336 S Y 338 A or rClfAP 336 A Y 338 S.

2. The method of claim 1 , wherein, in the recombinant fibrinogen binding protein clumping factor A (ClfA) according to (b), amino acid residues Ala 254 , Tyr 256 , Ile 387 , Lys 389 , Glu 526 and/or Val 527 are substituted with either Ala or Ser.

3. The method of claim 1 , wherein the recombinant fibrinogen binding protein clumping factor A (ClfA) consists of the fibrinogen binding region (c) or (d).

Assignees

• Foster Timothy
• Higgins Judy
• Josefsson Elisabet
• Geoghegan Joan
• Dequesne Guy
• Tarkowski Andrej
• Andersson Carlake
• Glaxosmithkline Biolog Sa
• Trinity College Dublin

Inventors

• Foster Timothy
• Higgins Judy
• Josefsson Elisabet
• Geoghegan Joan
• Dequesne Guy
• Tarkowski Andrej

Classifications

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P37/04

  Immunostimulants · CPC title

• A61P31/04

  Antibacterial agents · CPC title

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title