National Research Council of Canada

The Brigham and Women's Hospital, Inc.

Canadian Patents & Development Ltd.

Harvard College

Baxter International Inc.

Harold J Jennings

Francis Michon

Dennis L Kasper

Robert Pon

Michele Lussier

Christopher L Penney

Vince Pozsgay

Rene Roy

Czeslaw Lugowski

Robert J Chalifour

Robert Feldman

Martial Lacroix

Michael R Wessels

Nancy J Levy

Andrzej Gamian

The invention relates to chemically-modified group B polysaccharides of . The invention also provides vaccines in which the respective modified polysaccharides are conjugated to a protein carrier, and the like. More specifically, the present invention provides novel group B meningococcal unsaturated N-acyl derivative polysaccharides, novel conjugates of the group B meningococcal unsaturated N-acyl derivative polysaccharides, pharmaceutical compositions comprising conjugate molecules of group B meningococcal unsaturated N-acyl derivative polysaccharide fragments covalently bound to proteins, and the use of these compositions as vaccines.

Meningococcal polysaccharide conjugate vaccines

The invention relates to chemically-modified group B polysaccharides of . The invention also provides vaccines in which the respective modified polysaccharides are conjugated to a protein carrier, and the like, as well as antibodies to these conjugate vaccines. More specifically, the present invention provides novel group B meningococcal unsaturated N-acyl derivative polysaccharides, novel conjugates of the group B meningococcal unsaturated N-acyl derivative polysaccharides, pharmaceutical compositions comprising conjugate molecules of group B meningococcal unsaturated N-acyl derivative polysaccharide fragments covalently bound to proteins, and the use of these compositions as vaccines.

Antibodies to meningococcal polysaccharide conjugate vaccines

This invention relates to antigenic conjugate molecules comprising the capsular polysaccharide of Group B streptococcus type II which are covalently linked to protein. This invention further relates to antigenic conjugate molecules comprising the capsular polysaccharide of Group B streptococcus type V which are covalently linked to protein. This invention also relates to vaccines and methods of immunizing mammals, including humans against infection by Group B streptococcus type II (GBS II) and/or Group B streptococcus type V (GBS V). Multivalent vaccines comprising the conjugate molecules of this invention and antigens to other pathogenic bacteria are also claimed.

Group B streptococcus type II and type V polysaccharide-protein

The invention relates to chemically-modified group B polysaccharides of Neisseria meningitidis. The invention also provides vaccines in which the respective modified polysaccharides are conjugated to a protein carrier, and the like. More specifically, the present invention provides novel group B meningococcal unsaturated N-acyl derivative polysaccharides, novel conjugates of the group B meningococcal unsaturated N-acyl derivative polysaccharides, pharmaceutical compositions comprising conjugate molecules of group B meningococcal unsaturated N-acyl derivative polysaccharide fragments covalently bound to proteins, and the use of these compositions as vaccines.

Neisseria meningitidis group B polysaccharide (GBMP) modified by having sialic acid residue N-acetyl groups replaced by N-acyl groups exhibits enhanced immuno response thereto. In addition, induction of antibodies which cross-react with unmodified group B meningococcal and E. coli K1 capsular polysaccharide and other tissue cells having a common epitope is minimized. Conjugation of the modified polysaccharides with a physiologically acceptable protein such as tetanus toxoid induces the production of specific protective antibodies with negligible levels of GBMP-cross reactive antibodies, to thereby afford protection against infections caused by group B meningococci and E. coli K1.

Meningococcal polysaccharide conjugate vaccine

This invention relates to antigenic conjugate molecules comprising the capsular polysaccharide of Group B streptococcus type II which are covalently linked to protein. This invention also relates to vaccines and methods of immunizing mammals, including humans against infection by Group B streptococcus type II (GBS II). Multivalent vaccines comprising the conjugate molecules of this invention and antigens to other pathogenic bacteria are also claimed.

Group B streptococcus type II polysaccharide-tetanus toxoid conjugate

Modified meningococcal polysaccharide conjugate vaccines

Group B streptococcus type V polysaccharide-protein conjugate vaccines

Improved vaccine compositions comprising a long chain alkyl compound as an immunoadjuvant in combination with a bacterial polysaccharide protein conjugate. The compositions of the invention are useful in activating the immune system to confer immunity to a host against the immunogen in a prophylactic manner.

Vaccine compositions

Antigens and vaccines containing purified oligomers (1-50 units) of the repeating pentasaccharide unit of type III Group B Stretococcus (III GBS) polysaccharide capsule. Methods of making the antigen by recovering polysaccharide from cultured III GBS or medium and digesting the polysaccharide with a specific endo-.beta.-galactosidase. Enzymatic cleavage of bacterial polysaccharide to make purified oligomers. A purified trypsin-resistant C surface protein, m.w. about 14,000 and vaccine. Passive immunization using the above vaccines. Immunoassays for GBS immunodeterminants or anti-GBS antibodies.

Bacterial antigens, antibodies, vaccines and methods of manufacture

Immunoadsorbent combinations for the detection and diagnosis of group B streptococcus polysaccharide antigen, comprising an insoluble carrier, a capture agent having an affinity for specifically binding to the trirhamnose epitope of group B streptococcus antigen and having the formula .alpha.-L-Rhap(1.fwdarw.2)-.alpha.-L-Rhap(1.fwdarw.2).alpha.-Rhap- 1- wherein Rhap is rhamnose, and an antigen marker agent having an affinity for binding to monorhamnose epitope of group B streptococcus polysaccharide antigen of formula .alpha.-L-Rhap-1- when the group B streptococcus polysaccharide is bound to the carrier. An immunoassay method test kit and polyclonal antibody are also described.

Immunoassay for detecting group B streptococcus

The group B polysaccharide of Neisseria meningitidis is chemically modified to enhance the immune response thereto, thereby providing cross-reactive antibodies of high affinity. The N-acetyl group of the sialic acid residues of the polysaccharide has been substituted by the N-propionyl group, and this modified antigen then conjugated to a physiologically-acceptable protein such as tetanus toxoid. This conjugate vaccine has been found to raise high titers of high affinity group B IgG antibodies and would be useful against meningitis caused by group B N. meningitidis or by E. coli KI organisms.

Modified meningococcal group B polysaccharide for conjugate vaccine

Antigenic polysaccharides are modified to generate a terminally-located aldehyde group by controlled oxidation of vicinal hydroxyl groups, e.g. of unlinked terminal non-reducing sialic acid residues. In some cases where there is a reducing end group, e.g. of the type N-acetylmannosamine residue, it can be made into the most susceptible site for oxidation by initially reducing it to its open chain hydroxyl form, e.g. N-acetylmannosaminitol. The vicinal hydroxyl oxidation is controlled to yield a reactive aldehyde group which is then covalently linked to a free amino group of a selected protein by reductive amination. The resulting polysaccharide-protein conjugates are soluble and have been found to have enhanced antigenicity compared to the polysaccharide alone. This terminal aldehyde:free amine group reductive amination can be applied to various polysaccharide antigens and various well-tolerated proteins, preferably protein immunogens. For example, meningococcal group A, B and C polysaccharides have been linked to tetanus toxoid to give soluble conjugates which have been found to have advantageous immunogenic properties.

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Gloucester, Canada

Harold J Jennings