Reduction of Free Polysaccharide Contamination in the Production of a 15-valent Pneumococcal Conjugate Vaccine

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2020 Dec 10

PMID 33301525

Authors

Yoon Hee Whang

Soo Kyung Kim

Hyeseon Yoon

Seuk Keun Choi

Yeong Ok Baik

Chankyu Lee

Inhwan Lee

Affiliations

Soon will be listed here.

Abstract

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®.

Citing Articles

Further Insights into the Measurement of Free Polysaccharide in Meningococcal Conjugate Vaccines.

Beresford N, De Benedetto G, Lockyer K, Gao F, Burkin K, Lalwani K Vaccines (Basel). 2025; 13(2).

PMID: 40006714 PMC: 11861164. DOI: 10.3390/vaccines13020167.

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