Reduction of free polysaccharide contamination in the production of a 15-valent pneumococcal conjugate vaccine.

Glycoconjugate vaccines are vaccines in which a bacterial polysaccharide antigen is conjugated to a carrier protein to enhance immunogenicity by promoting T cell-dependent immune response. However, the free (unreacted) polysaccharides remaining after the conjugation process can inhibit the immunogen...

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Main Authors: Yoon Hee Whang, Soo Kyung Kim, Hyeseon Yoon, Seuk Keun Choi, Yeong Ok Baik, Chankyu Lee, Inhwan Lee
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2020-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0243909
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author Yoon Hee Whang
Soo Kyung Kim
Hyeseon Yoon
Seuk Keun Choi
Yeong Ok Baik
Chankyu Lee
Inhwan Lee
author_facet Yoon Hee Whang
Soo Kyung Kim
Hyeseon Yoon
Seuk Keun Choi
Yeong Ok Baik
Chankyu Lee
Inhwan Lee
author_sort Yoon Hee Whang
collection DOAJ
description Glycoconjugate vaccines are vaccines in which a bacterial polysaccharide antigen is conjugated to a carrier protein to enhance immunogenicity by promoting T cell-dependent immune response. However, the free (unreacted) polysaccharides remaining after the conjugation process can inhibit the immunogenicity of a conjugate vaccine. Thus, we aimed to reduce the unbound free polysaccharides in the polysaccharide-protein conjugation process for the development of a new 15-valent pneumococcal conjugate vaccine (PCV15) by varying some factors that may affect the conjugation results such as polysaccharide/protein ratio, polysaccharide size, and concentration of a coupling agent in a conjugation reaction mixture. Concentrations of a coupling agent, carbodiimide (EDAC), and a carrier protein (CRM197) used in PCV15 production, during the conjugation process, had little effect on the content of free polysaccharides. However, the size of the polysaccharide was identified as the critical factor to control the free polysaccharide content, with an inverse relationship observed between the molecular weight of the polysaccharide and the residual free polysaccharide content after conjugation. Based on these results, a new PCV15 with low free polysaccharide contamination was produced and tested for immunogenicity using a rabbit model to show that it induces similar level of immune responses in rabbits compared to a comparator vaccine Prevnar13®.
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spelling doaj.art-f580eca06e6d416bbf5f3f5cd9711db42022-12-21T21:30:50ZengPublic Library of Science (PLoS)PLoS ONE1932-62032020-01-011512e024390910.1371/journal.pone.0243909Reduction of free polysaccharide contamination in the production of a 15-valent pneumococcal conjugate vaccine.Yoon Hee WhangSoo Kyung KimHyeseon YoonSeuk Keun ChoiYeong Ok BaikChankyu LeeInhwan LeeGlycoconjugate vaccines are vaccines in which a bacterial polysaccharide antigen is conjugated to a carrier protein to enhance immunogenicity by promoting T cell-dependent immune response. However, the free (unreacted) polysaccharides remaining after the conjugation process can inhibit the immunogenicity of a conjugate vaccine. Thus, we aimed to reduce the unbound free polysaccharides in the polysaccharide-protein conjugation process for the development of a new 15-valent pneumococcal conjugate vaccine (PCV15) by varying some factors that may affect the conjugation results such as polysaccharide/protein ratio, polysaccharide size, and concentration of a coupling agent in a conjugation reaction mixture. Concentrations of a coupling agent, carbodiimide (EDAC), and a carrier protein (CRM197) used in PCV15 production, during the conjugation process, had little effect on the content of free polysaccharides. However, the size of the polysaccharide was identified as the critical factor to control the free polysaccharide content, with an inverse relationship observed between the molecular weight of the polysaccharide and the residual free polysaccharide content after conjugation. Based on these results, a new PCV15 with low free polysaccharide contamination was produced and tested for immunogenicity using a rabbit model to show that it induces similar level of immune responses in rabbits compared to a comparator vaccine Prevnar13®.https://doi.org/10.1371/journal.pone.0243909
spellingShingle Yoon Hee Whang
Soo Kyung Kim
Hyeseon Yoon
Seuk Keun Choi
Yeong Ok Baik
Chankyu Lee
Inhwan Lee
Reduction of free polysaccharide contamination in the production of a 15-valent pneumococcal conjugate vaccine.
PLoS ONE
title Reduction of free polysaccharide contamination in the production of a 15-valent pneumococcal conjugate vaccine.
title_full Reduction of free polysaccharide contamination in the production of a 15-valent pneumococcal conjugate vaccine.
title_fullStr Reduction of free polysaccharide contamination in the production of a 15-valent pneumococcal conjugate vaccine.
title_full_unstemmed Reduction of free polysaccharide contamination in the production of a 15-valent pneumococcal conjugate vaccine.
title_short Reduction of free polysaccharide contamination in the production of a 15-valent pneumococcal conjugate vaccine.
title_sort reduction of free polysaccharide contamination in the production of a 15 valent pneumococcal conjugate vaccine
url https://doi.org/10.1371/journal.pone.0243909
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