Improving protein glycan coupling technology (PGCT) for glycoconjugate vaccine production

ABSTRACT

Introduction

Vaccines are one of the great success stories of modern medicine and an increasingly important strategy in the fight against antimicrobial resistance. Glycoconjugate vaccines, consisting of a protein component covalently linked to a glycan antigen, are extremely efficacious in preventing infectious disease. However, glycoconjugates have yet to reach their full potential, with currently licensed glycoconjugate vaccines available against only four pathogens. Protein glycan coupling technology, where glycoconjugates are biologically produced in purpose engineered bacterial cells, has the potential to revolutionize the field by lowering manufacturing cost and increasing flexibility for tailor-made vaccines.

Areas covered

This review gives an overview of the past 20 years of PGCT research, discusses the key developments and current status of the technology, and speculates on the future of PGCT-based vaccinology.

Expert opinion

PCGT has the potential to overcome some of the limitations of chemical conjugation production methods. The technology has undergone significant development since its inception, and new discoveries are continually driving the field forward. Vaccines currently in clinical trials have demonstrated the potential of the PGCT to deliver effective glycoconjugate vaccines for unmet medical needs.

KEYWORDS:

• Bacterial vaccines
• bioconjugation
• glycoconjugate vaccines
• glycoengineering
• PGCT

Article highlights

• Glycoconjugate vaccines are safe, effective and an important tool for reducing the incidence of diseases caused by antibiotic-resistant pathogens.

• Despite the success of glycoconjugate vaccines, chemical conjugation methods are complex and expensive and few are currently licensed and in use.

• Protein Glycan Coupling Technology (PGCT), also known as bioconjugation, is an alternative approach to produce glycoconjugates that involves the expression and biological conjugation of proteins and glycans within purpose-engineered cells, via the use of bacterial coupling enzymes.

• PCGT-based vaccines against a range of bacterial pathogens have been tested in animals, and some of these have proceeded to phase 2 clinical trials.

• Significant technological developments have been implemented to improve the efficiency and versatility of PGCT, including identifying novel and modifying existing coupling enzymes, optimizing recombinant protein and glycan expression, and engineering of the host bacterial strain.

• The predicted cost and efficiency advantages of PGCT could open up new markets for glycoconjugate vaccines, including veterinary vaccines, and could enable more rapid responses to disease outbreaks.

• Despite some technical, economic, and regulatory hurdles to be overcome, the future for PGCT vaccinology looks bright.

Acknowledgments

The authors would like to thank Dr. Jon Cuccui for his comments on the manuscript.

Author contributions

J M Dow, M Mauri, and T Scott contributed equally to the writing of this review. B Wren provided critical feedback on the manuscript.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

We acknowledge funding from BBSRC, MRC and EPSRC.