The Rockefeller University

Medimmune Limited

St. Jude Children's Research Hospital

The Rockfeller University

H Robert Masure

Elaine I Tuomanen

Theresa M Wizemann

Carsten I Rosenow

Leslie Sydnor Johnson

Scott Koenig

Barbara J Pearce

This invention provides an isolated polypeptide comprising an amino acid sequence of a N-terminal choline binding protein A truncate in which the amino acid sequence is set forth in any of SEQ ID NOS: 1, 3-7, or 9-11, including fragments, mutants, variants, analogs, or derivatives, thereof. Also, this invention provides a isolated polypeptide comprising an amino acid sequence of a N-terminal choline binding protein A truncate, wherein the amino acid is set forth in SEQ ID NO: 24, wherein the polypeptide retains its native tertiary structure and methods of preparation. This invention provides an isolated polypeptide comprising an amino acid sequence of a N-terminal choline binding protein A truncate, wherein the polypeptide has lectin activity and does not bind to choline. This invention provides an isolated immunogenic polypeptide comprising an amino acid sequence of a N-terminal choline binding protein A truncate. This invention provides an isolated nucleic acid encoding a polypeptide comprising an amino acid sequence of a N-terminal choline binding protein A truncate. Lastly, this invention provides pharmaceutical compositions, vaccines, and diagnostic and therapeutic methods of use.

Polypeptide comprising the amino acid of an N-terminal choline binding protein a truncate, vaccine derived therefrom and uses thereof

The invention relates to bacterial choline binding proteins (CBPs) which bind choline. Such proteins are particularly desirable for vaccines against appropriate strains of Gram positive bacteria, particularly, and more particularly. Also provided are DNA sequences encoding the bacterial choline binding proteins or fragment thereof, antibodies to the bacterial choline binding proteins, pharmaceutical compositions comprising the bacterial choline binding proteins, antibodies to the bacterial choline binding proteins suitable for use in passive immunization, and small molecule inhibitors of choline binding protein mediated adhesion. Methods for diagnosing the presence of the bacterial choline binding protein, or of the bacteria, are also provided. In a specific embodiment, a streptococcal choline binding protein is an enolase, which demonstrates strong affinity for fibronectin.

Choline binding proteins for anti-pneumococcal vaccines

This invention provides an isolated polypeptide comprising an amino acid sequence of a N-terminal choline binding protein A truncate in which the amino acid sequence is set forth in any of SEQ ID NOS: 1, 3-7, or 9-11, including fragments, mutants, variants, analogs, or derivatives, thereof. Also, this invention provides a isolated polypeptide comprising an amino acid sequence of a N-terminal choline binding protein A truncate, wherein the amino acid is set forth in SEQ ID NO 24, wherein the polypeptide retains its native tertiary structure and methods of preparation. This invention provides an isolated polypeptide comprising an amino acid sequence of a N-terminal choline binding protein A truncate, wherein the polypeptide has lectin activity and does not bind to choline. This invention provides an isolated immunogenic polypeptide comprising an amino acid sequence of a N-terminal choline binding protein A truncate. This invention provides an isolated nucleic acid encoding a polypeptide comprising an amino acid sequence of a N-terminal choline binding protein A truncate. Lastly, this invention provides pharmaceutical compositions, vaccines, and diagnostic and therapeutic methods of use.

The invention relates to bacterial choline binding proteins (CBPs) which bind choline. Such proteins are particularly desirable for vaccines against appropriate strains of Gram positive bacteria, particularly streptococcus, and more particularly pneumococcus. Also provided are DNA sequences encoding the bacterial choline binding proteins or fragment thereof, antibodies to the bacterial choline binding proteins, pharmaceutical compositions comprising the bacterial choline binding proteins, antibodies to the bacterial choline binding proteins suitable for use in passive immunization, and small molecule inhibitors of choline binding protein mediated adhesion. Methods for diagnosing the presence of the bacterial choline binding protein, or of the bacteria, are also provided. In a specific embodiment, a streptococcal choline binding protein is an enolase, which demonstrates strong affinity for fibronectin.

Peptides which will inhibit the reaction between the RGD tripeptide of FHA and the integrin receptors of endothelial cells and their utility as therapeutic agents are described.

Antibody recognizing endothelial cell ligand for leukocyte CR3

Bacterial exported proteins and acellular vaccines based thereon

Peptides which inhibit adhesion between leukocytes and endothelial cells

The present invention relates to the identification of Gram positive bacterial exported proteins, and the genes encoding such proteins. In particular, the invention relates to adhesion associated exported proteins, and to antigens common to many or all strains of a species of Gram positive bacterium. The invention also relates to acellular vaccines to provide protection from Gram positive bacterial infection using such genes or such proteins, and to antibodies against such proteins for use in diagnosis and passive immune therapy. In specific embodiments, fragments of ten genes encoding exported proteins of S. pneumoniae are disclosed, and the functional activity of some of these proteins in adherence is demonstrated.

The present invention relates to the identification of a bacterial adhesion associated protein, and the gene encoding such protein. More particularly, the invention relates to a pneumococcal peptide methionine sulfoxide reductase involved in bacterial adherence. The invention also relates to identification and development of agents to provide protection from bacterial infection based on this protein. The invention provides nucleic acids encoding the peptide methionine sulfoxide reductase, as well as methods for identifying antagonists of the methionine sulfoxide reductase. The present invention further demonstrates that peptide methionine sulfoxide reductase is an adhesion-associated protein in various Gram-negative and Gram-positive bacteria and accordingly provides for interference with the peptide methionine sulfoxide reductase to inhibit bacterial adherence to host tissues.

Bacterial peptide methionine sulfoxide reductase an adhesion-associated

Selectin and pertussis toxin derived peptides and uses thereof

Bacterial peptide methionine sulfoxide reductase, and

Peptides and antibodies which will inhibit the reaction between the RGD tripeptide of FHA and the integrin receptors of endothelial cells and their utility as therapeutic agents and a method of increasing the permeability of the blood-brain barrier using an antibody to the Arg-Gly-Asp (RGD) region of filamentous hemagglutinin (FHA) are described.

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New York, NY, United States of America

H Robert Masure