Connaught Laboratories Limited

Aventis Pasteur Limited

Other

University of Toronto

Sanofi Pasteur Inc.

Washington University

Aventis Pasteur Limited/aventus Pasteur Limitee

Pele Chong

Michel Henri Klein

Sheena M Loosmore

Yan-Ping Yang

Raymond P Oomen

Robin E Harkness

Andrew D Murdin

Anthony Bernard Schryvers

Charles D Sia

Scott Gray-Owen

Ali Kandil

Kenneth K Sokoll

Raafat Emil Fahim

Larry U Tan

Gail E Jackson

Yan Ping Yang

Wayne Thomas

Olive A James

John Vose

Ken Sasaki

Michel H Klein

Patrick McVerry

Emil F Pai

Robert S Munson, Jr

Alf Lindberg

Arthur Pedyczak

Shirley Gillam

Dawei Ou

Aubrey Tingle

Dwo Yuan Sia

Lee W Riley

Charles D Y Sia

Susan Grass

Dwo Yan Charles Sia

Robert Tolan

Dw&oslash; Yuan Charles Sia

Dwe Yuan Sia

The crystal structure of the Fab' fragment of Mab 2F5, a potent neutralizer of both laboratory strains and primary clinical isolates of most clades of HIV-1, both uncompleted and complexed with the largely conserved peptide sequence ELDKWAS of the viral envelope protein gp41, has been elucidated and the characteristics of peptide-protein interactions determined. Having regard to such determination, the peptide-mimetics are constrained in the three-dimensional structure to provide an increased immunogenicity to the epitope sequence.

Fab-epitope complex from the HIV-1 cross-neutralizing monoclonal antibody 2F5

Purified and isolated nucleic acid is provided which encodes a transferrin receptor protein of a strain ofor a fragment or an analog of the transferrin receptor protein. The nucleic acid sequence may be used to produce peptides free of contaminants derived from bacteria normally containing the Tbp1 or Tbp2 proteins for purposes of diagnostics and medical treatment. Furthermore, the nucleic acid molecule may be used in the diagnosis of infection. Also provided are recombinant Tbp1 or Tbp2 and methods for purification of the same. Live vectors expressing epitopes of transferrin receptor protein for vaccination are provided.

Transferrin receptor genes

A method of generating an HIV-specific cytotoxic T-cell response in a host involves an initial administration of a T-helper molecule to the host to prime T-helper cells of the immune system of the host and a subsequent administration to the host of a mixture of the T-helper molecule and a T-cell inducing HIV-derived molecule to generate an HIV-specific T-cell response in the host.

HIV-specific cytotoxic T-cell responses

Multivalent immunogenic molecules comprise a carrier molecule containing at least one functional T-cell epitope and multiple different carbohydrate fragments each linker to the carrier molecule and each containing at least one functional B-cell epitope. The carrier molecule inputs enhanced immunogenicity to the multiple carbohydrate fragments. The carbohydrate fragments may be capsular oligosaccharide fragments from, which may be serotypes 1, 4, 5, 6B, 9V, 14, 18C, 19F or 23F, or, which may be serotype A, B, C, W-135 or Y. Such oligosaccharide fragments may be sized from 2 to 5 kDa. Alternatively, the carbohydrate fragments may be fragments of carbohydrate-based tumor antigens, such as Globo H, Leor STn. The multivalent molecules may be produced by random conjugation or site-directed conjugation of the carbohydrate fragments to the carrier molecule. The multivalent molecules may be employed in vaccines or in the generation of antibodies for diagnostic application.

Multi-oligosaccharide glycoconjugate bacterial meningitis vaccines

Adjuvant compositions for modulating an immune response to an antigen administered to a host comprise a mineral salt adjuvant and at least one other adjuvant. The compositions provide an adjuvanting effect on an antigen which is greater than the adjuvanting effect attainable by one of the adjuvants alone. An antigen is covalently bonded to a glycolipid analog to provide a discrete molecule which exhibits an enhanced adjuvanting effect on the antigen which is greater than the adjuvanting effect attainable in the absence of such covalent bonding.

Adjuvant compositions containing more than one adjuvant

Multivalent immunogenic molecules comprise a carrier molecule containing at least one functional T-cell epitope and multiple different carbonhydrate fragments each linked to the carrier molecule and each containing at least one functional B-cell epitope. The carrier molecule inparts enhanced immunogenicity to the multiple carbohydrate fragments. The carbohydrate fragments may be capsular oligosaccharide fragments from which may be serotypes (1, 4, 5, 6B, 9V, 14, 18C, 19F or 23F), or , which may be serotype (A, B, C) W-135 or Y. Such oligosaccharide fragments may be sized from about 2 to about 5 kDa. Alternatively, the carbohydrate fragments may be fragments of carbohydrate-based tumor antigens, such as Globo H, Le or STn. The multivalent molecules may be produced by random conjugation or site-directed conjugation of the carbohydrate fragments to the carrier molecule. The multivalent molecules may be employed in vaccines or in the generation of antibodies for diagnostic applications.

Multi oligosaccharide glycoconjugate bacterial meningitis vaccines

Copolymers designed for use as particulate carriers containing functionalizable amino acid subunits for coupling with targeting ligands are described. The copolymers are polyesters composed of &agr;-hydroxy acid subunits such as D,L-lactide and pseudo-&agr;-amino acid subunits which may be derived from serine or terpolymers of D,L-lactide and glycolide and pseudo-&agr;-amino acid subunits which may be derived from serine. Stable vaccine preparations useful as delayed release formulations containing antigen or antigens and adjuvants encapsulated within or physically mixed with polymeric mircoparticles are described. The particulate carriers are useful for delivering agents to the immune system of a subject by mucosal or parenteral routes to produce immune responses, including antibody and protective responses.

Biodegradable targetable microparticle delivery system

The crystal structure of the Fab&prime; fragment of Mab 2F5, a potent neutralizer of both laboratory strains and primary clinical isolates of most clades of HIV-1, both uncompleted and completed with the largely conserved peptide sequence ELDKWAS of the viral envelope protein gp41, has been elucidated and the characteristics of peptide-protein interactions determined. Having regard to such determination, the peptide-mimetics are constrained in the three-dimensional structure to provide an increased immunogenicity to the epitope sequence.

Fab&prime;-epitope complex from HIV-1 cross-neutralizing monoclonal antibody 2F5

Copolymers designed for use as particulate carriers containing functionalizable amino acid subunits for coupling with targeting ligand are described. The copolymers are polyesters composed of &agr;-hydroxy acid subunits such as D,L-lactide and &agr;-amino acid subunits such as serine or in the preferred embodiment, terpolymers of D,L-lactide and glycolide and &agr;-amino acid subunits such as serine. Stable vaccine preparations useful as delayed release formulations containing antigen(s) or antigen(s) and co-adjuvants encapsulated within or physically mixed with polymeric microparticles are described. The particulate carriers are useful for delivering agents to the immune system of a subject by mucosal or parenteral routes to produce immune responses, including antibody responses.

An isolated and purified outer membrane protein of a Moraxella strain, particularly , having a molecular mass of about 200 kDa, is provided. The about 200 kDa outer membrane protein as well as nucleic acid molecules encoding the same are useful in diagnostic applications and immunogenic compositions, particularly for in vivo administration to a host to confer protection against disease caused by a bacterial pathogen that produces the about 200 kDa outer membrane protein or produces a protein capable of inducing antibodies in a host specifically reactive with the about 200 kDa outer membrane protein.

High molecular weight major outer membrane protein of moraxella

Pertactin (formerly 69 kDa protein) is recovered in stable biologically pure form having no detectable adenylate cyclase activity from fermentation broth from the fermentation of as well as from the cells. The broth is processed to selectively remove pertussis toxin (PT) and filamentous haemagglutinin (FHA), the pertactin is precipitated by ammonium sulphate and the precipitate is dissolved in buffer at pH 6.0 to 8.5, the solution then is passed through hydroxyapatite and ion-exchange chromatograph columns before final ultrafiltration. Cells are extracted with urea and the extract ultrafiltered and diafiltered. The pertactin is precipitated from the extract and the precipitate processed as above. In a variation, the broth is contacted with ammonium sulphate to precipitate pertactin, PT and FHA, the precipitate is dissolved and the PT and FHA selectively removed, before the solution is passed to the chromatograph columns.

Purification of a pertussis outer membrane protein

An isolated and purified outer membrane protein of a Moraxella strain, particularly having a molecular mass of about 200 kDa, is provided. The about 200 kDa outer membrane protein as well as nucleic acid molecules encoding the same are useful in diagnostic applications and immunogenic compositions, particularly for in vivo administration to a host to confer protection against disease caused by a bacterial pathogen that produces the about 200 kDa outer membrane protein or produces a protein capable of inducing antibodies in a host specifically reactive with the about 200 kDa outer membrane protein.

Purified and isolated nucleic acid is provided which encodes a transferrin receptor protein of a strain of Haemophilus or a fragment or an analog of the transferrin receptor protein. The nucleic acid sequence may be used to produce peptides free of contaminants derived from bacteria normally containing the Tbp1 or Tbp2 proteins for purposes of diagnostics and medical treatment. Furthermore, the nucleic acid molecule may be used in the diagnosis of infection. Also provided are recombinant Tbp1 or Tbp2 and methods for purification of the same. Live vectors expressing epitopes of transferrin receptor protein for vaccination are provided.

Purified and isolated nucleic acid is provided which encodes a transferrin receptor protein of a strain of Haemophilus or a fragment or an analog of the transferrin receptor protein. The nucleic acid sequence may be used to produce peptides free of contaminants derived from bacteria normally containing the Tbp1 or Tbp2 proteins for purposes of diagnostics and medical treatment. Furthermore, the nucleic acid molecule may be used in the diagnosis of infection. Also provided are recombinant Tbpl or Tbp2 and methods for purification of the same. Live vectors expressing epitopes of transferrin receptor protein for vaccination are provided.

Growing community of inventors

Richmond Hill, Canada

Pele Chong