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A solid-phase conjugation method was developed and applied to the synthesis of an O-antigen based glycoconjugate vaccine against Salmonella Typhimurium, with CRM197 as the carrier protein. Copper-free click chemistry was used as the conjugation chemistry, after derivatizing the sugar and the protein components with alkyne and azido linkers, respectively. This chemistry has the advantage of not deactivating functional groups during the conjugation step, thereby allowing the recycling of unreacted components. The activated carrier protein was adsorbed to an anion exchange matrix and quantitatively conjugated to the O-antigen. The resulting conjugate was eluted from the resin free of unconjugated sugar which was previously removed by simple washing steps. Unreacted O-antigen was recycled by addition to a new batch of resin-CRM197 resulting in further quantitative protein conjugation. This process has advantages in relation to reduction of costs for production of conjugate vaccines, allowing unreacted sugar recovery and simplifying the purification of the glycoconjugate.

Original publication

DOI

10.1021/acs.bioconjchem.5b00521

Type

Journal article

Journal

Bioconjug Chem

Publication Date

16/12/2015

Volume

26

Pages

2507 - 2513

Keywords

Bacterial Proteins, Click Chemistry, Glycoconjugates, Humans, Models, Molecular, O Antigens, Salmonella Infections, Salmonella typhimurium, Solid-Phase Synthesis Techniques, Vaccines, Conjugate