Title:
MUTANT CHOLESTEROL-BINDING CYTOLYSIN PROTEINS
Document Type and Number:
WIPO Patent Application WO/2005/108419
Kind Code:
A1
Abstract:
The invention relates to immunogenic compositions comprising mutant cytolysin proteins. The invention further relates to such proteins and nucleic acids encoding these proteins. In particular embodiments, the invention is directed to an isolated mutant cytolysin protein, wherein the mutant protein differs from the wild type protein by the deletion of one or more amino acids within the region corresponding to amino acids 144 to 161 of the wild type pneumolysin sequence. In certain embodiments, the mutant protein differs from the wild type protein by the deletion of one or more amino acids within the region corresponding to amino acids 144 to 151 of the wild type pneumolysin sequence. In particular embodiments, the mutant protein differs from the wild type protein by the deletion of two adjacent amino acids within the region corresponding to amino acids 144 to 151 of the wild type pneumolysin sequence.
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Inventors:
KIRKHAM LEA-ANN (GB)
MITCHELL TIMOTHY JOHN (GB)
COWAN GRAEME JAMES MACFARLANE (GB)
MITCHELL TIMOTHY JOHN (GB)
COWAN GRAEME JAMES MACFARLANE (GB)
Application Number:
PCT/GB2005/001774
Publication Date:
November 17, 2005
Filing Date:
May 09, 2005
Export Citation:
Assignee:
KIRKHAM LEA-ANN (GB)
MITCHELL TIMOTHY JOHN (GB)
COWAN GRAEME JAMES MACFARLANE (GB)
MITCHELL TIMOTHY JOHN (GB)
COWAN GRAEME JAMES MACFARLANE (GB)
International Classes:
A61K39/02; C07K14/195; C07K14/315; (IPC1-7): C07K14/195; A61K39/02
Domestic Patent References:
| WO1990006951A1 | 1990-06-28 |
Foreign References:
| US20010014332A1 | 2001-08-16 |
Other References:
HILL J ET AL: "AMINO ACIDS IN PNEUMOLYSIN IMPORTANT FOR HEMOLYTIC ACTIVITY IDENTIFIED BY RANDOM MUTAGENESIS", INFECTION AND IMMUNITY, AMERICAN SOCIETY FOR MICROBIOLOGY. WASHINGTON, US, vol. 62, no. 2, February 1994 (1994-02-01), pages 757 - 758, XP001194645, ISSN: 0019-9567
HOTZE EILEEN M ET AL: "Monomer-monomer interactions drive the prepore to pore conversion of a beta-barrel-forming cholesterol-dependent cytolysin", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 277, no. 13, 29 March 2002 (2002-03-29), pages 11597 - 11605, XP002341458, ISSN: 0021-9258
RAMACHANDRAN RAJESH ET AL: "Membrane-dependent conformational changes initiate cholesterol-dependent cytolysin oligomerization and intersubunit beta-strand alignment", NATURE STRUCTURAL & MOLECULAR BIOLOGY, vol. 11, no. 8, August 2004 (2004-08-01), pages 697 - 705, XP002341459, ISSN: 1545-9993
ALEXANDER JANET E ET AL: "Amino acid changes affecting the activity of pneumolysin alter the behaviour of pneumococci in pneumonia", MICROBIAL PATHOGENESIS, vol. 24, no. 3, March 1998 (1998-03-01), pages 167 - 174, XP002341460, ISSN: 0882-4010
LOCK ROBERT A ET AL: "Sequence variation in the Streptococcus pneumoniae pneumolysin gene affecting haemolytic activity and electrophoretic mobility of the toxin", MICROBIAL PATHOGENESIS, vol. 21, no. 2, 1996, pages 71 - 83, XP002341461, ISSN: 0882-4010
HOTZE EILEEN M ET AL: "Monomer-monomer interactions drive the prepore to pore conversion of a beta-barrel-forming cholesterol-dependent cytolysin", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 277, no. 13, 29 March 2002 (2002-03-29), pages 11597 - 11605, XP002341458, ISSN: 0021-9258
RAMACHANDRAN RAJESH ET AL: "Membrane-dependent conformational changes initiate cholesterol-dependent cytolysin oligomerization and intersubunit beta-strand alignment", NATURE STRUCTURAL & MOLECULAR BIOLOGY, vol. 11, no. 8, August 2004 (2004-08-01), pages 697 - 705, XP002341459, ISSN: 1545-9993
ALEXANDER JANET E ET AL: "Amino acid changes affecting the activity of pneumolysin alter the behaviour of pneumococci in pneumonia", MICROBIAL PATHOGENESIS, vol. 24, no. 3, March 1998 (1998-03-01), pages 167 - 174, XP002341460, ISSN: 0882-4010
LOCK ROBERT A ET AL: "Sequence variation in the Streptococcus pneumoniae pneumolysin gene affecting haemolytic activity and electrophoretic mobility of the toxin", MICROBIAL PATHOGENESIS, vol. 21, no. 2, 1996, pages 71 - 83, XP002341461, ISSN: 0882-4010
Attorney, Agent or Firm:
Forrest, Graham (York House 23 Kingsway, London Greater London WC2B 6HP, GB)
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