Sugar–Protein Connectivity Impacts on the Immunogenicity of Site‐Selective Salmonella O‐Antigen Glycoconjugate Vaccines. (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. Volume 127:Number 45(2015)
• Page Start: 13396
• Page End: 13401
• Publication Date: 2015-09-09
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201506112
• Languages: English
• ISSNs: 0044-8249

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>A series of glycoconjugates with defined connectivity were synthesized to investigate the impact of coupling <italic>Salmonella</italic> 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.</p> </abstract>