Sugar-Protein Connectivity Impacts on the Immunogenicity of Site-Selective Salmonella O-Antigen Glycoconjugate Vaccines.

Angewandte Chemie
G StefanettiFrancesca Micoli

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.

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Citations

May 29, 2016·Glycobiology·Lina SunFikri Y Avci
May 18, 2016·Experimental Biology and Medicine·Mia L HuangKamil Godula
Jan 23, 2016·Chemical Society Reviews·Qi-Ying HuRoberto Adamo
Jul 19, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Simon S ParkJacquelyn Gervay-Hague
Feb 9, 2016·Chembiochem : a European Journal of Chemical Biology·Takuya Machida, Nicolas Winssinger
Nov 13, 2018·Organic & Biomolecular Chemistry·Anish MistryMartin Wills
Aug 3, 2016·Chemistry : a European Journal·Hiroki HamagamiHiroshi Tanaka
Aug 5, 2017·Chembiochem : a European Journal of Chemical Biology·Philipp R SpycherRoger Schibli
Jun 20, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Francesca MicoliPaolo Costantino
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Nov 19, 2019·Frontiers in Chemistry·Aline PillotCyrille Grandjean
Jul 18, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Cinzia ColomboLuigi Lay
Jul 7, 2020·Expert Review of Vaccines·Jennifer Mhairi DowBrendan William Wren
May 18, 2017·Organic & Biomolecular Chemistry·Alessandro Del GrossoMartin Wills
Nov 19, 2020·International Journal of Molecular Sciences·Roberta Di BenedettoFrancesca Micoli
May 3, 2021·The FEBS Journal·Marko AnderluhSandra J van Vliet
Jul 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Cristina Bolzati, Barbara Spolaore
May 4, 2017·Accounts of Chemical Research·Roberto Adamo
Apr 27, 2018·Bioconjugate Chemistry·Gianluigi De BenedettoFrancesca Micoli
Sep 23, 2021·Expert Review of Vaccines·Henderson ZhuAndrew J Pollard

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Methods Mentioned

BETA
acylation
glycosylation

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