Immunogenic polysaccharide-protein conjugates

US4356170A · kind A · utility

Assignee

• Canadian Patents and Development Limited · CA

Inventors

• Harold J. Jennings · Ottawa, CA
• Czeslaw Lugowski · Wrocław, PL

Key dates

• Filing date: May 27, 1981
• Grant date: Oct 26, 1982
• Expiry date: May 27, 2001

Classification

• Technology area (CPC Y): Emerging Cross-Sectional Technologies
• CPC primary: Y10S530/825
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

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.