Sugar–Protein Connectivity Impacts on the Immunogenicity of Site‐Selective Salmonella O‐Antigen Glycoconjugate Vaccines. Issue 45 (9th September 2015)

• Record Type: Journal Article
• Authors: Stefanetti, Giuseppe; Hu, Qi‐Ying; Usera, Aimee; Robinson, Zack; Allan, Martin; Singh, Alok; Imase, Hidetomo; Cobb, Jennifer; Zhai, Huili; Quinn, Douglas; Lei, Ming; Saul, Allan; Adamo, Roberto; MacLennan, Calman A.; Micoli, Francesca
• Is Part Of: Angewandte Chemie international edition. Volume 54:Issue 45(2015)
• Page Start: 13198
• Page End: 13203
• Publication Date: 2015-09-09
• Subjects: carbohydrates -- glycoproteins -- protein modification -- solmonella -- vaccines; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201506112
• Languages: English
• ISSNs: 1433-7851

Abstract

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. Abstract : A vaccine against salmonella : Two methods are reported for the preparation of site‐selective glycoconjugate vaccines with one single sugar chain linked to one or two precise positions of the CRM197 carrier protein (see picture; OAg=O‐Antigen). The point of linkage on the protein plays a role in determining the immunogenicity of the glycoconjugate vaccines in mice.