Oligosaccharide-protein conjugate: A novel approach for making Salmonella O-antigen immunogens

Electron beam fragmentation of bacterial polysaccharides as a method of producing oligosaccharides for the preparation of conjugate vaccines

“…These conjugates are crosslinked, have a very high molecular mass and are difficult to define on a molecular level. The second type of PS‐protein conjugates consists of shorter PS fragments attached to the protein at one point, usually utilizing the chemical feature of their terminal groups [8, 13–15]. End‐group conjugates are non‐crosslinked, their synthesis is easy to control and the final product can be well defined by simple biochemical means.…”

“…Hence PnPSs as such are not capable of inducing IgG responses, booster effects and immunological memory in young individuals [6]. Chemical conjugation to immunogenic proteins, however, converts antigenic epitopes of PnPSs into T‐helper cell dependent (TD) antigens: such polysaccharide‐protein conjugate vaccines are therefore fully immunogenic and afford efficient protection also in infants [7–10].…”

“…Several methods of partial depolymerization of bacterial and non‐bacterial PSs are described which yield fragments suitable for conjugation, such as acid hydrolysis [16], oxidation by periodate [17], ozonolysis [18], limited hydrolysis by endoglycanases of viral [8, 13] or bacterial origin [19], and sonication [20–22]. All these methods suffer from limitations: acid hydrolysis and periodation sometimes have deleterious effects on labile antigenic epitopes of some PSs, ozonolysis can only be used with PSs containing β‐ d ‐aldosidic linkages, and only few endoglycanases have been isolated to date that due to their high specificity can be used only with a very limited number of PSs.…”

Artificial Salmonella vaccines: O-antigenic oligosaccharide-protein conjugates induce protection against infection with Salmonella typhimurium

“…Previously, Paul et al (21) showed that pneumococcal SI,, polysaccharide-protein conjugates augmented the antibody response in rabbits against the SI,, polysaccharide and suggested that the use of bacterial polysaccharide-protein conjugates could be of value for immunoprophylaxis. We have previously used a similar approach and prepared nontoxic Salmonella 0-antigenic oligosaccharide-protein conjugates (26)(27)(28). The 0antigen polysaccharide chains of partially delipidated Salmonella typhimurium LPS were cleaved by bacteriophage P22-associated endorhamnosidase (27; U. Eriksson, S. B. Svenson, J. Lonngren, and A.…”

Electron beam fragmentation of bacterial polysaccharides as a method of producing oligosaccharides for the preparation of conjugate vaccines

“…Several methods of partial depolymerization of bacterial and non-bacterial PSs are described which yield fragments suitable for conjugation, such as acid hydrolysis [16], oxidation by periodate [17], ozonolysis [18], limited hydrolysis by endoglycanases of viral [8,13] or bacterial origin [19], and sonication [202 2]. All these methods su¡er from limitations: acid hydrolysis and periodation sometimes have deleterious e¡ects on labile antigenic epitopes of some PSs, ozonolysis can only be used with PSs containing L-Daldosidic linkages, and only few endoglycanases have been isolated to date that due to their high speci¢city can be used only with a very limited number of PSs.…”