Antibody-mediated disruption of quorum sensing in bacteria

Patent metadata

Field	Value
Publication number	US-9394371-B2
Application number	US-73427308-A
Country	US
Kind code	B2
Filing date	Oct 24, 2008
Priority date	Oct 25, 2007
Publication date	Jul 19, 2016
Grant date	Jul 19, 2016

Abstract

The invention provides an immunogenic molecular entity, a supramolecular assembly, and an antibody that can be used to inhibit Gram-positive bacterial quorum sensing, prevent infection or development of a disease condition associated with a Gram-positive bacterial infection. The invention also provides methods of inhibiting Gram-positive bacterial quorum sensing, and methods of preventing infection or development of a disease condition associated with a Gram-positive bacterial infection.

First claim

What is claimed is:

1. An immunogenic molecular entity comprising at least one hapten covalently linked to a macromolecular carrier, wherein the hapten comprises a cyclic peptide comprising a macrocyclic ring, wherein the cyclic peptide comprises the amino acid sequence of YST(X a+2 )DFIM (SEQ ID: 92); wherein the last amino acid residue is covalently bonded to a group R by a respective carbonyl group; X a+2 is any amino acid, a respective carbon atom of which is covalently bonded to R; wherein R comprises —CH 2 O—, —CH 2 CH 2 O—, —CH 2 CH(CH 3 )O—, —CH 2 -phenyl-O—, —CH 2 S—, —CH 2 CH 2 S—, or —(CH 2 ) n NH—, wherein n is 1 to about 4; the N-terminal amino acid residue of the cyclic peptide is attached to the macromolecular carrier.

2. The immunogenic molecular entity of claim 1 , wherein the macromolecular carrier comprises a protein, a polymer or a nanoparticle.

3. The immunogenic molecular entity of claim 2 , wherein the macromolecular carrier comprises a protein.

4. The immunogenic molecular entity of claim 1 , wherein the cyclic peptide is covalently linked to the macromolecular carrier.

5. An immunogenic molecular entity having the structure:

SEQ ID NO: 3 (YSTSDFIM, not including protecting groups),
wherein CPL, is a macromolecular carrier with linker covalently bonded to a cysteine thiol group.

6. A vaccine composition comprising at least one immunogenic molecular entity of claim 1 and a pharmaceutically-acceptable carrier.

7. A method of eliciting an immune response in a mammal comprising administering to the mammal a composition comprising the immunogenic molecular entity of claim 1 , in an amount effective to elicit an immune response in the mammal; wherein the mammal is susceptible to infection by Staphylococcus aureus.

8. A method of inhibiting quorum sensing in a mammal comprising administering to the mammal the immunogenic molecular entity of claim 1 , in an amount effective to elicit an immune response and inhibit the quorum sensing in the mammal.

9. A method for treating infection of a mammal by Staphylococcus aureus , comprising administering to the mammal the immunogenic molecular entity of claim 1 in an amount effective to treat infection of the mammal by Staphylococcus aureus.

Assignees

• Janda Kim D
• Kaufmann Gunnar F
• Park Junguk
• Scripps Research Inst

Inventors

• Janda Kim D
• Kaufmann Gunnar F
• Park Junguk

Classifications

• A61P31/04

  Antibacterial agents · CPC title

• A61P37/04

  Immunostimulants · CPC title

• C07K5/04

  containing only normal peptide links · CPC title

• C07K16/1271 Primary

  Micrococcaceae (F); Staphylococcaceae (F), e.g. Staphylococcus (G) · CPC title

• C07K16/44 Primary

  against material not provided for elsewhere {, e.g. haptens, metals, DNA, RNA, amino acids} · CPC title