Hu, Qi-Ying and Usera, Aimee (2015) Sugar-Protein Connectivity Impacts on the Immunogenicity of Site-Selective Salmonella O-Antigen Glycoconjugate Vaccines. Angewandte Chemie (International ed. in English), 54 (45). pp. 13198-13203. ISSN 1521-3773

Abstract

A series of glycoconjugates with defined connectivity were synthesized to investigate the impact of coupling Salmonella typhimurium O-antigen to different amino acids of CRM197 protein carrier. In particular, two novel methods for site-selective glycan conjugation were developed to obtain conjugates with single attachment site on the protein, based on chemical modification of a disulfide bond and pH-controlled transglutaminase-catalyzed modification of lysine, respectively. Importantly, conjugation at the C186-201 bond resulted in significantly higher anti O-antigen bactericidal antibody titers than coupling to K37/39, and in comparable titers to conjugates bearing a larger number of saccharides. This study demonstrates that the conjugation site plays a role in determining the immunogenicity in mice and one single attachment point may be sufficient to induce high levels of bactericidal antibodies.

Item Type:	Article
Keywords:	carbohydrates glycoproteins protein modification solmonella vaccines
Date Deposited:	25 Nov 2017 00:45
Last Modified:	25 Jan 2019 00:45
URI:	https://oak.novartis.com/id/eprint/26802