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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...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
WILEY-VCH Verlag
2015
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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. |
format | Online Article Text |
id | pubmed-4648054 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | WILEY-VCH Verlag |
record_format | MEDLINE/PubMed |
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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