Polysaccharide-Protein Conjugate Vaccines

It is to Karl Landsteiner that we owe the notion that the immunologic properties of nonimmunogenic ligands (haptens), including saccharides, can be improved by covalent attachment to proteins [1]. His pioneering studies in the 1920s influenced Walter Goebel and Oswald Avery (his colleague at the Rockefeller Institute, NY) who sought evidence that serum antibodies to the type 3 capsular polysaccharide (CP) of pneumococci conferred protection to that pathogen [2]. These workers showed that a synthetic disaccharide (hapten), cellubiuronic acid, bound to a protein could elicit antibodies that were both reactive with the type 3 CP and conferred protection to mice challenged with that pathogen. At that time, purification of individual components of bacteria was difficult and high-titered antisera were prepared by intravenous injections of whole bacteria: such serologic reagents were multivalent. Their studies provided convincing evidence that CPs were both essential virulence factors and protective antigens of pneumococci.