Connaught Laboratories Limited

Aventis Pasteur Limited

Ali Kandil

Michel Henri Klein

Pele Chong

Yan-Ping Yang

Charles D Sia

Olive A James

Lucy Gisonni

Raafat Emil Fahmy Fahim

Raafat Emil Fahim

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

Immunogenic conjugate molecules comprising at least a portion of a capsular polysaccharide of a Streptococcus strain linked to at least a portion of an outer membrane protein of a Haemophilus strain are provided in which the immunogenicity of the capsular polysaccharide is increased. Particularly capsular polysaccharide from,are linked to an outer membrane protein of a,strain, which protein may be the P1, P2 or particularly the P6 outer membrane protein. Conjugate molecules comprising the P6 protein linked to a capsular polysaccharide from an encapsulated pathogen other than Streptococcus also are described, in which the immunogenicity of the capsular polysaccharide is enhanced. Such conjugate molecules may be incorporated into immunogenic compositions for protecting a host against disease caused by the Streptococcus strain and preferably also the Haemophilus strain. The conjugate molecules and antibodies specific for the capsular polysaccharide or specific for the outer membrane protein may be employed in diagnostic procedures and kits. A process for individually isolating P1, P2 and P6 outer membrane proteins from a Haemophilus strain also is provided.

Immunogenic conjugate molecules

Adjuvant compositions comprising a mineral salt and another immunostimulating compound

Generation of immune response using immunogenic conjugate of molecules

Capsular polysaccharides containing multiple sialic acid residues, particularly the Group B polysaccharide of Neisseria meningitidis, are modified by chemical reaction to randomly introduce pendant reactive residues of heterobifunctional linker molecules to the polysaccharide backbone. The capsular polysaccharide is deacetylated and the heterobifunctional linker molecule is reacted with the deacetylated material and any residual amino groups are blocked by reaction with alkyl acid anhydride. The introduction of the linker molecules to the polysaccharide chain between the termini enables the polysaccharide to be linked to a carrier molecule, such as a protein, to enhance the immunogenicity of the polysaccharide. The conjugate molecule may be formulated as an immunogenic composition for raising antibodies in a host to the polysaccharide.

Neisseria meningitidis capsular polysacchride conjugates

Synthetic Haemophilus influenzae conjugate vaccine

Polyribosylribitol phosphate oligosaccharides are produced in a multistep process. The compound of the formula: ##STR1## wherein R.sub.1 is a first protecting group and R.sub.2 is a second protecting group, is coupled to a solid polyethylene glycol monomethyl ether (PEG) support. Following removal of the first protecting group, the resulting compound is coupled with a repeating unit for chain elongation of the formula: ##STR2## The protecting group is removed from the phosphorus atom and the steps of removing the first protecting group, coupling with the repeating unit is repeated until the desired number of repeating units in the oligomer has been terminated. The oligomer then is terminated with a chain terminating molecule of the formula: ##STR3## wherein m is an integer and R.sub.3 is a third protecting group. The resulting PEG-bound protected oligomer is a new product and the oligomer may be cleaved from the support and processed to provide a chemically-reactive functional group for binding the polysaccharide oligomer to a carrier molecule.

Synthesis of polyribosylribitol phosphate oligosaccharides

Adjuvant compositions

Neisseria meningitidis capsular polysaccharide conjugates

Immunogenic conjugate molecules comprising at least a portion of a capsular polysaccharide of a Streptococcus strain linked to at least a portion of an outer membrane protein of a Haemophilus strain are provided in which the immunogenicity of the capsular polysaccharide is increased. Particularly capsular polysaccharide from Streptococcus pneumoniae are linked to an outer membrane protein of a Haemophilus influenzae strain, which protein may be the P1, P2 or particularly the P6 outer membrane protein. Conjugate molecules comprising the P6 protein linked to a capsular polysaccharide from an encapsulated pathogen other than Streptococcus also are described, in which the immunogenicity of the capsular polysaccharide is enhanced. Such conjugate molecules may be incorporated into immunogenic compositions for protecting a host against disease caused by the Streptococcus strain and preferably also the Haemophilus strain. The conjugate molecules and antibodies specific for the capsular polysaccharide or specific for the outer membrane protein may be employed in diagnostic procedures and kits. A process for individually isolating P1, P2 and P6 outer membrane proteins from a Haemophilus strain also is provided.

Synthetic peptides have an amino acid sequence corresponding to at least one antigenic determinant of at least one protein, usually a structural protein, particularly the P1, P2 and P6 protein, of Haemophilus influenzae (Hi), particularly type b, and are used as is, in chimeric T-B form, in lipidated form, linked to a carrier molecule, particularly a synthetic PRP molecule and/or polymerized to form molecular aggregates, in vaccines against Hi.

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Willowdale, Canada

Ali Kandil