Conjugation Strategies Used for the Preparation of Carbohydrate‐Conjugate Vaccines

Hevey, Rachel; Ling, Chang‐Chun

doi:10.1002/9781118775882.ch16

Cited by 7 publications

(8 citation statements)

References 161 publications

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“…One of the most implemented conjugation methods in glycoconjugate vaccine production is via reductive amination [118,119]. Licensed vaccines conjugating via this method include CPS-based conjugate vaccines against 13 serotypes of S. pneumoniae (Prevnar13; Pfizer, USA).…”

Section: Reductive Aminationmentioning

confidence: 99%

“…Several conjugation chemistries are available for LPS-based glycoconjugate vaccines, but some resulted in the loss of immunogenicity or manufacturability. In most instances, conjugation chemistries will aim to introduce suitable linkers to reduce steric hindrance between sugar and peptide moieties, while also preserving the relevant epitopes in the resultant glycoconjugates [81,119]. To satisfy these aims, methods including reductive amination, CDAP chemistry, and aminooxyoxime chemistry have been more extensively incorporated in LPS-based glycoconjugate vaccine candidates than other techniques [114,118,120,144].…”

Section: Expert Opinionsmentioning

confidence: 99%

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Recent advances in lipopolysaccharide-based glycoconjugate vaccines

Zhu

Rollier

Pollard

2021

Expert Review of Vaccines

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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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Section: Reductive Aminationmentioning

confidence: 99%

Section: Expert Opinionsmentioning

confidence: 99%

Recent advances in lipopolysaccharide-based glycoconjugate vaccines

Zhu

Rollier

Pollard

2021

Expert Review of Vaccines

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“…In addition to the C -glycosides, other atoms or groups have been used to substitute the glycosidic linkage, aiming for an ideal balance between hydrolytic stability and conformational pre-organization. These include various N -linked glycosides, as well as selenium, sulfur, and even dithioacetal analogues (Figure 13) [32,110,111,112,113,114].…”

Section: Glycomimetic Design—strategies To Improve Pharmacokineticmentioning

confidence: 99%

“…Interestingly, glycomimetics have also been used as antigens in carbohydrate-conjugate vaccines [32,33,34,35,36,37]. The non-native, glycomimetic structures have been observed to enhance immunogenicity, and if designed properly can elicit the production of antibodies that are cross-reactive with native glycans.…”

Section: Introductionmentioning

confidence: 99%

Strategies for the Development of Glycomimetic Drug Candidates

Hevey

2019

Pharmaceuticals

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Carbohydrates are a structurally-diverse group of natural products which play an important role in numerous biological processes, including immune regulation, infection, and cancer metastasis. Many diseases have been correlated with changes in the composition of cell-surface glycans, highlighting their potential as a therapeutic target. Unfortunately, native carbohydrates suffer from inherently weak binding affinities and poor pharmacokinetic properties. To enhance their usefulness as drug candidates, ‘glycomimetics’ have been developed: more drug-like compounds which mimic the structure and function of native carbohydrates. Approaches to improve binding affinities (e.g., deoxygenation, pre-organization) and pharmacokinetic properties (e.g., limiting metabolic degradation, improving permeability) have been highlighted in this review, accompanied by relevant examples. By utilizing these strategies, high-affinity ligands with optimized properties can be rationally designed and used to address therapies for novel carbohydrate-binding targets.

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“…For interactions where no chemical transformation occurs upon binding, such as those involving lectins, an enhancement in target binding affords lower K d values and typically stronger biological responses. In glycomimetics serving as antigens in carbohydrate-based conjugate vaccines, non-native ligands can afford enhanced immunogenicity over their native counterparts, resulting in elevated antibody titers and improved vaccine constructs [32,39,40,41].…”

Section: Introductionmentioning

confidence: 99%

Bioisosteres of Carbohydrate Functional Groups in Glycomimetic Design

Hevey

2019

Biomimetics

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The aberrant presentation of carbohydrates has been linked to a number of diseases, such as cancer metastasis and immune dysregulation. These altered glycan structures represent a target for novel therapies by modulating their associated interactions with neighboring cells and molecules. Although these interactions are highly specific, native carbohydrates are characterized by very low affinities and inherently poor pharmacokinetic properties. Glycomimetic compounds, which mimic the structure and function of native glycans, have been successful in producing molecules with improved pharmacokinetic (PK) and pharmacodynamic (PD) features. Several strategies have been developed for glycomimetic design such as ligand pre-organization or reducing polar surface area. A related approach to developing glycomimetics relies on the bioisosteric replacement of carbohydrate functional groups. These changes can offer improvements to both binding affinity (e.g., reduced desolvation costs, enhanced metal chelation) and pharmacokinetic parameters (e.g., improved oral bioavailability). Several examples of bioisosteric modifications to carbohydrates have been reported; this review aims to consolidate them and presents different possibilities for enhancing core interactions in glycomimetics.

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Conjugation Strategies Used for the Preparation of Carbohydrate‐Conjugate Vaccines

Cited by 7 publications

References 161 publications

Recent advances in lipopolysaccharide-based glycoconjugate vaccines

Recent advances in lipopolysaccharide-based glycoconjugate vaccines

Strategies for the Development of Glycomimetic Drug Candidates

Bioisosteres of Carbohydrate Functional Groups in Glycomimetic Design

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