Recent advances in the production of recombinant glycoconjugate vaccines

Emily Kay,Jon Cuccui,Brendan W Wren

doi:10.1038/s41541-019-0110-z

Emily Kay, Jon Cuccui + Show 1 more

Open Access

https://doi.org/10.1038/s41541-019-0110-z

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Abstract

Glycoconjugate vaccines against bacteria are one of the success stories of modern medicine and have led to a significant reduction in the global occurrence of bacterial meningitis and pneumonia. Glycoconjugate vaccines are produced by covalently linking a bacterial polysaccharide (usually capsule, or more recently O-antigen), to a carrier protein. Given the success of glycoconjugate vaccines, it is surprising that to date only vaccines against Haemophilus influenzae type b, Neisseria meningitis and Streptococcus pneumoniae have been fully licenced. This is set to change through the glycoengineering of recombinant vaccines in bacteria, such as Escherichia coli, that act as mini factories for the production of an inexhaustible and renewable supply of pure vaccine product. The recombinant process, termed Protein Glycan Coupling Technology (PGCT) or bioconjugation, offers a low-cost option for the production of pure glycoconjugate vaccines, with the in-built flexibility of adding different glycan/protein combinations for custom made vaccines. Numerous vaccine candidates have now been made using PGCT, which include those improving existing licenced vaccines (e.g., pneumococcal), entirely new vaccines for both Gram-positive and Gram-negative bacteria, and (because of the low production costs) veterinary pathogens. Given the continued threat of antimicrobial resistance and the potential peril of bioterrorist agents, the production of new glycoconjugate vaccines against old and new bacterial foes is particularly timely. In this review, we will outline the component parts of bacterial PGCT, including recent advances, the advantages and limitations of the technology, and future applications and perspectives.

Highlights

Glycoconjugate vaccines are traditionally made by chemical activation of the polysaccharide at random sites, or at the reducing end,[7] followed by conjugation to a carrier protein
The carrier protein is de-activated Corynebacterium diphtheria toxin 197 (CRM197), which has recently been made available as a cloned product.[8]
In the case of glycOMVs, the intrinsic adjuvant properties of outer membrane vesicles (OMVs) and the flexibility of lipid A choice holds promise for the generation of a self-adjuvanting, non-toxic delivery system for carbohydrate antigens.[13,14]. Discussions on these strategies is beyond the scope of this review, which will focus on the construction and production of recombinant glycoconjugate vaccines by glycoengineering using Protein Glycan Coupling Technology (PGCT)

Summary

INTRODUCTION

A defining characteristic of a successful vaccine is the ability to evoke long-lasting protective immunity with minimal side effects. Glycoconjugate vaccines are traditionally made by chemical activation of the polysaccharide at random sites, or at the reducing end,[7] followed by conjugation to a carrier protein This process requires initial steps to purify the glycan polysaccharide from the pathogenic organism, against which the vaccine is targeted, including removal of contaminating endotoxin, and purification of the acceptor protein from the organism of choice. In the case of glycOMVs, the intrinsic adjuvant properties of OMVs and the flexibility of lipid A choice holds promise for the generation of a self-adjuvanting, non-toxic delivery system for carbohydrate antigens.[13,14] Discussions on these strategies is beyond the scope of this review, which will focus on the construction and production of recombinant glycoconjugate vaccines by glycoengineering using Protein Glycan Coupling Technology (PGCT). The original genome sequencing of the human gastrointestinal pathogen Campylobacter jejuni (strain NCTC 11168) in early 2000

Kay et al 2

CONCLUSION AND FUTURE PERSPECTIVES