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Updated: Oct 19, 2025

Homogeneous Glycoconjugate Produced by Combined Unnatural Amino Acid Incorporation and Click-Chemistry for Vaccine Purposes
Published on: December 19, 2020
Recent advances in lipopolysaccharide-based glycoconjugate vaccines
Henderson Zhu1, Christine S Rollier1, Andrew J Pollard1
1Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the National Institute for Health Research (Nihr) Oxford Biomedical Research Centre, Oxford, UK.
Introduction:
The public health burden caused by pathogenic Gram-negative bacteria is increasingly prominent due to antimicrobial resistance. The surface carbohydrates are potential antigens for vaccines against Gram-negative bacteria. The enhanced immunogenicity of the O-specific polysaccharide (O-SP) moiety of LPS when coupled to a carrier protein may protect against bacterial pathogens. However, because of the toxic lipid A moiety and relatively high costs of O-SP isolation, LPS has not been a popular vaccine antigen until recently.
Areas Covered:
In this review, we discuss the rationales for developing LPS-based glycoconjugate vaccines, principles of glycoconjugate-induced immunity, and highlight the recent developments and challenges faced by LPS-based glycoconjugate vaccines.
Expert Opinion:
Advances in LPS harvesting, LPS chemical synthesis, and newer carrier proteins in the past decade have propelled LPS-based glycoconjugate vaccines toward further development, through to clinical evaluation. The development of LPS-based glycoconjugates offers a new horizon for vaccine prevention of Gram-negative bacterial infection.
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