Combined effects of glycan chain length and linkage type on the immunogenicity of glycoconjugate vaccines

Abstract

The development and use of antibacterial glycoconjugate vaccines have significantly reduced the occurrence of potentially fatal childhood and adult diseases such as bacteremia, bacterial meningitis, and pneumonia. In these vaccines, the covalent linkage of bacterial glycans to carrier proteins augments the immunogenicity of saccharide antigens by triggering T cell-dependent B cell responses, leading to high-affinity antibodies and durable protection. Licensed glycoconjugate vaccines either contain long-chain bacterial polysaccharides, medium-sized oligosaccharides, or short synthetic glycans. Here, we discuss factors that affect the glycan chain length in vaccines and review the available literature discussing the impact of glycan chain length on vaccine efficacy. Furthermore, we evaluate the available clinical data on licensed glycoconjugate vaccine preparations with varying chain lengths against two bacterial pathogens, Haemophilus influenzae type b and Neisseria meningitidis group C, regarding a possible correlation of glycan chain length with their efficacy. We find that long-chain glycans cross-linked to carrier proteins and medium-sized oligosaccharides end-linked to carriers both achieve high immunogenicity and efficacy. However, end-linked glycoconjugates that contain long untethered stretches of native glycan chains may induce hyporesponsiveness by T cell-independent activation of B cells, while cross-linked medium-sized oligosaccharides may suffer from suboptimal saccharide epitope accessibility.

Influence of Natural Polysaccharides on Intestinal Microbiota in Inflammatory Bowel Diseases: An Overview

“…Although NPs have been demonstrated to inhibit the activation of several inflammatory signaling pathways, no direct evidence of SCFAs produced by NPs fermentation with inflammatory responses or expression of peroxisome proliferator-activated receptor has been presented. In addition, glycan chain length and linkage type have been found to influence the immunogenicity and efficacy of glycoconjugate vaccines [130]; however, their structure-activity relationship in terms of IBD remains poorly understood. Furthermore, the bioavailability of NPs should be investigated to better understand their utilization in human body.…”

Scale‐up issues during sterile filtration of glycoconjugate vaccines

“…The coupling of specific capsular polysaccharides to an immunogenic carrier protein provides induction of both B‐cell and T‐cell immunity leading to an improved long‐term immune response 2 . Anish et al 3 reported that long‐chain polysaccharides that are cross‐linked to the carrier protein medium‐length polysaccharides in an end‐linked configuration typically provide the highest immunogenicity.…”

Scale-Up of Capsular Polysaccharide Production Process by Haemophilus influenzae Type b Using kLa Criterion

“…and culture conditions (pH, temperature, oxygen tension, etc.) [ 56 ] in order to consider that all fermentation performances were maintained under the k L a criterion scale-up process. The results in Table 3 showed that the PRP obtained presents an average MW about 347.2 kDa, while the MW of native PRP reported in a previous study was found between 450 and 600 kDa [ 55 ].…”