Glycoconjugate vaccines against antimicrobial resistant pathogens

ABSTRACT

Introduction

Antimicrobial resistance (AMR) is responsible for the death of millions worldwide and stands as a major threat to our healthcare systems, which are heavily reliant on antibiotics to fight bacterial infections. The development of vaccines against the main pathogens involved is urgently required as prevention remains essential against the rise of AMR.

Areas covered

A systematic research review was conducted on MEDLINE database focusing on the six AMR pathogens defined as ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Escherichia coli), which are considered critical or high priority pathogens by the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC). The analysis was intersecated with the terms carbohydrate, glycoconjugate, bioconjugate, glyconanoparticle, and multiple presenting antigen system vaccines.

Expert opinion

Glycoconjugate vaccines have been successful in preventing meningitis and pneumoniae, and there are high expectations that they will play a key role in fighting AMR. We herein discuss the recent technological, preclinical, and clinical advances, as well as the challenges associated with the development of carbohydrate-based vaccines against leading AMR bacteria, with focus on the ESKAPE pathogens. The need of innovative clinical and regulatory approaches to tackle these targets is also highlighted.

KEYWORDS:

• Antimicrobial resistance
• ESKAPE
• carbohydrates
• infection
• glycoconjugates
• vaccines
• bioconjugates
• multiple presenting antigen system

Article highlights

• Developing vaccines against ESKAPE pathogens is a critical priority, as these pathogens are major contributors to AMR, posing a severe threat to public health.

• Carbohydrate-based vaccines harnessing bacterial glycans could be instrumental in the fight against drug-resistant pathogens.

• A deeper understanding of glycoimmunology is crucial and would help comprehend how glycoconjugates work, paving the way for more effective vaccine development.

• The development of effective bacterial vaccines faces multiple challenges, including the need for new technologies and analytical tools to ensure vaccine quality and deliverability.

• The challenging identification of target populations to assess clinical efficacy and impact on AMR is calling for new clinical design and regulatory approaches.

Declaration of interests

C Sorieul is a PhD student at Leiden University and a former employee of GSK in the context of the industrial EU program Horizon 2020 PAVax, grant no 861194. M Dolce is a PhD student and participated in a post graduate studentship program at GSK in collaboration with the University of Siena. M Rosaria Romano and R Adamo are employees of the GSK group of companies. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or material discussed in the manuscript apart from those disclosed.

Reviewer disclosures

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

Acknowledgments

Figures 1 to were created with BioRender.com. Carbohydrate structures from Figure 4 were generated with the CSDB/SNFG structure editor.

Author contributions

All authors have substantially contributed to the conception and design of the review article and interpreting the relevant literature, and have been involved in writing the review article or revised it for intellectual content.

Additional information

Funding

This manuscript was funded by EU program Horizon 2020 through grant no 861194 (PAVax). This work was sponsored by GlaxoSmithKline Biologicals SA.