An Overview of Structural Features of Antibacterial Glycoconjugate Vaccines That Influence Their Immunogenicity

Khatun, Farjana; Stephenson, Rachel J.; Tóth, István

doi:10.1002/chem.201603599

Cited by 46 publications

(30 citation statements)

References 143 publications

(146 reference statements)

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“… 2015 ; Khatun et al. 2017 ). The carrier protein is also derived from bacteria by fermentation and subsequent purification and, depending on the chemistry used, it can be conjugated via its functional groups or alternatively derivatized before polysaccharide linkage.…”

Section: Approaches For Production Of Glycoconjugate Vaccinesmentioning

confidence: 99%

Potential targets for next generation antimicrobial glycoconjugate vaccines

Micoli¹,

Costantino

Adamo

2018

FEMS Microbiology Reviews

139

109

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Cell surface carbohydrates have been proven optimal targets for vaccine development. Conjugation of polysaccharides to a carrier protein triggers a T-cell-dependent immune response to the glycan moiety. Licensed glycoconjugate vaccines are produced by chemical conjugation of capsular polysaccharides to prevent meningitis caused by meningococcus, pneumococcus and Haemophilus influenzae type b. However, other classes of carbohydrates (O-antigens, exopolysaccharides, wall/teichoic acids) represent attractive targets for developing vaccines. Recent analysis from WHO/CHO underpins alarming concern toward antibiotic-resistant bacteria, such as the so called ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.) and additional pathogens such as Clostridium difficile and Group A Streptococcus. Fungal infections are also becoming increasingly invasive for immunocompromised patients or hospitalized individuals. Other emergencies could derive from bacteria which spread during environmental calamities (Vibrio cholerae) or with potential as bioterrorism weapons (Burkholderia pseudomallei and mallei, Francisella tularensis). Vaccination could aid reducing the use of broad-spectrum antibiotics and provide protection by herd immunity also to individuals who are not vaccinated.This review analyzes structural and functional differences of the polysaccharides exposed on the surface of emerging pathogenic bacteria, combined with medical need and technological feasibility of corresponding glycoconjugate vaccines.

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Section: Approaches For Production Of Glycoconjugate Vaccinesmentioning

confidence: 99%

Potential targets for next generation antimicrobial glycoconjugate vaccines

Micoli¹,

Costantino

Adamo

2018

FEMS Microbiology Reviews

139

109

View full text Add to dashboard Cite

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“…Streptococcus pneumoniae is a global health concern for people of all ages, especially for the children and the elderly. All of the licenced pneumococcal glycoconjuagte vaccines are now derived form the natural polysaccharides . To develop new synthetic conjugate vaccines, various glycoconjugates have been prepared and evaluated.…”

Section: Synthetic Carbohydrate‐based Vaccinesmentioning

confidence: 99%

“…All of the licenced pneumococcal glycoconjuagte vaccines are now derived form the naturalp olysaccharides. [24] To develop new synthetic conjugate vaccines,v ariousg lycoconjugates have been prepared and evaluated. In 2008, Snippe and coworkers synthesized as eries of oligosaccharide fragments of Streptococcus pneumoniae type 14 capsularp olysaccharide (Pn14PS), rangingf rom tri-to dodecasaccharides.…”

Section: Synthetic Carbohydrate-based Vaccinesmentioning

confidence: 99%

Synthetic Glycans and Glycomimetics: A Promising Alternative to Natural Polysaccharides

Zhang

2018

Chemistry A European J

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A large quantity of polysaccharide-derived conjugate vaccines have been developed to combat various pathogenic infections. Another prominent polysaccharide, heparin, is listed as an essential drug by the World Health Organization (WHO) to treat thrombus. One of their common problems is that they all derive from natural polysaccharides. Specifically, capsular polysaccharides are mainly obtained from bacterial fermentation and unfractionated heparin is extracted from animal tissues such as porcine mucosa. The quality of natural polysaccharides is inconsistent and traces of contamination would cause a disaster. By contrast, the use of chemical or chemoenzymatic methods could provide structurally homogeneous and quality-controlled glycans. To date, large numbers of polysaccharide fragments and their analogues have been synthesized and evaluated. Some of them even showed comparable activities to their corresponding natural polysaccharides. Here, the latest advances in these synthetic glycan analogues ranging from carbohydrate-based vaccines, heparin-related therapeutics and glycomimetics of polysaccharides are summarized.

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“…5B). Prevnar13 containing glycoconjugates of multiple serotypes was utilized in this study as a reference, with the knowledge that the presence of additional serotypes can decrease the efficacy of individual serotypes in the vaccine (40,41).…”

Section: Significancementioning

confidence: 99%

Semisynthetic glycoconjugate vaccine candidate against Streptococcus pneumoniae serotype 5

Lisboa

Khan

Martin

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Glycoconjugate vaccines based on isolated capsular polysaccharide (CPS) save millions of lives annually by preventing invasive pneumococcal disease caused by Some components of the glycoconjugate vaccine Prevnar13 that contains CPS antigens from 13 serotypes undergo modifications or degradation during isolation and conjugation, resulting in production problems and lower efficacy. We illustrate how stable, synthetic oligosaccharide analogs of labile CPS induce a specific protective immune response against native CPS using serotype 5 (ST-5), a problematic CPS component of Prevnar13. The rare aminosugar l-PneuNAc and a branched l-FucNAc present in the natural repeating unit (RU) are essential for antibody recognition and avidity. The epitope responsible for specificity differs from the part of the antigen that is stabilized by chemical modification. Glycoconjugates containing stable, monovalent synthetic oligosaccharide analogs of ST-5 CPS RU induced long-term memory and protective immune responses in rabbits superior to those elicited by the ST-5 CPS component in multivalent Prevnar13.

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An Overview of Structural Features of Antibacterial Glycoconjugate Vaccines That Influence Their Immunogenicity

Cited by 46 publications

References 143 publications

Potential targets for next generation antimicrobial glycoconjugate vaccines

Potential targets for next generation antimicrobial glycoconjugate vaccines

Synthetic Glycans and Glycomimetics: A Promising Alternative to Natural Polysaccharides

Semisynthetic glycoconjugate vaccine candidate against Streptococcus pneumoniae serotype 5

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