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

A series of glycoconjugates with defined connectivity were synthesized to investigate the impact of coupling Salmonella typhimurium O-antigen to different amino acids of CRM(197) protein carrier. In particular, two novel methods for site-selective glycan conjugation were developed to obtain conjugat...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: WILEY-VCH Verlag 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4648054/
https://www.ncbi.nlm.nih.gov/pubmed/26350581
http://dx.doi.org/10.1002/anie.201506112
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author 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
author_facet 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
author_sort Stefanetti, Giuseppe
collection PubMed
description A series of glycoconjugates with defined connectivity were synthesized to investigate the impact of coupling Salmonella typhimurium O-antigen to different amino acids of CRM(197) 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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spelling pubmed-46480542015-11-24 Sugar–Protein Connectivity Impacts on the Immunogenicity of Site-Selective Salmonella O-Antigen Glycoconjugate Vaccines 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 Angew Chem Int Ed Engl Communications A series of glycoconjugates with defined connectivity were synthesized to investigate the impact of coupling Salmonella typhimurium O-antigen to different amino acids of CRM(197) 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. WILEY-VCH Verlag 2015-11-02 2015-09-09 /pmc/articles/PMC4648054/ /pubmed/26350581 http://dx.doi.org/10.1002/anie.201506112 Text en © 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. https://creativecommons.org/licenses/by-nc-nd/4.0/ © 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Communications
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
Sugar–Protein Connectivity Impacts on the Immunogenicity of Site-Selective Salmonella O-Antigen Glycoconjugate Vaccines
title Sugar–Protein Connectivity Impacts on the Immunogenicity of Site-Selective Salmonella O-Antigen Glycoconjugate Vaccines
title_full Sugar–Protein Connectivity Impacts on the Immunogenicity of Site-Selective Salmonella O-Antigen Glycoconjugate Vaccines
title_fullStr Sugar–Protein Connectivity Impacts on the Immunogenicity of Site-Selective Salmonella O-Antigen Glycoconjugate Vaccines
title_full_unstemmed Sugar–Protein Connectivity Impacts on the Immunogenicity of Site-Selective Salmonella O-Antigen Glycoconjugate Vaccines
title_short Sugar–Protein Connectivity Impacts on the Immunogenicity of Site-Selective Salmonella O-Antigen Glycoconjugate Vaccines
title_sort sugar–protein connectivity impacts on the immunogenicity of site-selective salmonella o-antigen glycoconjugate vaccines
topic Communications
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4648054/
https://www.ncbi.nlm.nih.gov/pubmed/26350581
http://dx.doi.org/10.1002/anie.201506112
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