Synthetically defined glycoprotein vaccines: current status and future directions

Adamo, Roberto; Nilo, Alberto; Castagner, Bastien; Boutureira, Omar; Berti, Francesco; Bernardes, Gonçalo J. L.

doi:10.1039/c3sc50862e

Cited by 138 publications

(124 citation statements)

References 117 publications

(149 reference statements)

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“…All such vaccines licensed to date are prepared in complex mixtures of heterogeneous polysaccharides, conjugated by different methods to the carrier protein 1. 2 Diphtheria toxoid (DT), nontoxic cross‐reactive material of diphtheria toxin (CRM 197 ), tetanus toxoid (TT) and the outer membrane protein complex (OMPC) of Neisseria meningitidis have been used in many of these vaccines, and have demonstrated excellent efficacy and safety 1. 2…”

Section: Introductionmentioning

confidence: 99%

Defined Conjugation of Glycans to the Lysines of CRM₁₉₇ Guided by their Reactivity Mapping

Crotti

Zhai²,

Zhou³

et al. 2014

ChemBioChem

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Systematic characterisation of the reactivity of the lysine moieties in CRM197 towards N-hydroxysuccinimide linkers bearing alkynes or azides is described. This involves two-step conjugation of various glycans to CRM197 by click chemistry in a well-defined manner. By semiquantitative LC-MS/MS analysis of proteolytic digests of the conjugates formed, the reactivity of lysine residues in the protein was mapped and ranked. Computational analysis of the solvent accessibility of each lysine residue (based on the CRM197 crystal structure) established a correlation between reactivity and surface exposure. By this approach, conjugation involving lysine residues (normally a random process) can be controlled. It enables the preparation of lysine-mediated glycoconjugates with improved batch-to-batch reproducibility, thereby producing neo-glycoconjugates with more-consistent biological activity.

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Section: Introductionmentioning

confidence: 99%

Defined Conjugation of Glycans to the Lysines of CRM₁₉₇ Guided by their Reactivity Mapping

Crotti

Zhai²,

Zhou³

et al. 2014

ChemBioChem

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“…[36] This new class of multivalent glycoconjugates could also provide promising antitumor-vaccine candidates in the future. [11c, 37] Applying the TMO-addition concept and click chemistry, trimeric globotriaose–PADRE conjugate 25 was constructed as a potential cancer-vaccine candidate (Scheme 8). Following the published protocol, [32, 38] compounds 20 and 24 [32] were reacted with sodium ascorbate, aminoguanidine, CuSO 4 ·5H 2 O, and tris(3-hydroxypropyltriazolylmethyl)amine ligand (THPTA) in PBS buffer pH 7.4 containing 5% DMSO, under O 2 -free conditions overnight.…”

Section: Resultsmentioning

confidence: 99%

Two‐Step Functionalization of Oligosaccharides Using Glycosyl Iodide and Trimethylene Oxide and Its Applications to Multivalent Glycoconjugates

Hsieh

Davis

Hoch

et al. 2014

Chemistry A European J

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Oligosaccharide conjugates, such as glycoproteins and glycolipids, are potential chemotherapeutics and also serve as useful tools for understanding the biological roles of carbohydrates. With many modern isolation and synthetic technologies providing access to a wide variety of free sugars, there is increasing need for general methodologies for carbohydrate functionalization. Herein, we report a two-step methodology for the conjugation of per-O-acetylated oligosaccharides to functionalized linkers that can be used for various displays. Oligosaccharides obtained from both synthetic and commercial sources were converted to glycosyl iodides and activated with I2 to form reactive donors that were subsequently trapped with trimethylene oxide to form iodopropyl conjugates in a single step. The terminal iodide served as a chemical handle for further modification. Conversion into the corresponding azide followed by copper-catalyzed azide–alkyne cycloaddition afforded multivalent glycoconjugates of Gb3 for further investigation as anti-cancer therapeutics.

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“…Current improvements in PS synthesis [18] and glyconanotechnology [19] might soon allow the production of synthetic PS vaccines [20]. Only few nanomaterials have been described as scaffolds for PS vaccines, among them gold glyconanoparticles.…”

Section: Pure Polysaccharide Vaccinesmentioning

confidence: 99%

From Immunologically Archaic to Neoteric Glycovaccines

Cavallari

Libero

2017

Vaccines

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Polysaccharides (PS) are present in the outermost surface of bacteria and readily come in contact with immune cells. They interact with specific antibodies, which in turn confer protection from infections. Vaccines with PS from pneumococci, meningococci, Haemophilus influenzae type b, and Salmonella typhi may be protective, although with the important constraint of failing to generate permanent immunological memory. This limitation has in part been circumvented by conjugating glycovaccines to proteins that stimulate T helper cells and facilitate the establishment of immunological memory. Currently, protection evoked by conjugated PS vaccines lasts for a few years. The same approach failed with PS from staphylococci, Streptococcus agalactiae, and Klebsiella. All those germs cause severe infections in humans and often develop resistance to antibiotic therapy. Thereby, prevention is of increasing importance to better control outbreaks. As only 23 of more than 90 pneumococcal serotypes and 4 of 13 clinically relevant Neisseria meningitidis serogroups are covered by available vaccines there is still tremendous clinical need for PS vaccines. This review focuses on glycovaccines and the immunological mechanisms for their success or failure. We discuss recent advances that may facilitate generation of high affinity anti-PS antibodies and confer specific immunity and long-lasting protection.

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Synthetically defined glycoprotein vaccines: current status and future directions

Abstract: We highlight current glycovaccines in the clinic and derive principles for the construction of the next generation of synthetically defined glycoconjugate vaccines.

Cited by 138 publications

References 117 publications

Defined Conjugation of Glycans to the Lysines of CRM₁₉₇ Guided by their Reactivity Mapping

Defined Conjugation of Glycans to the Lysines of CRM₁₉₇ Guided by their Reactivity Mapping

Two‐Step Functionalization of Oligosaccharides Using Glycosyl Iodide and Trimethylene Oxide and Its Applications to Multivalent Glycoconjugates

From Immunologically Archaic to Neoteric Glycovaccines

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Synthetically defined glycoprotein vaccines: current status and future directions

Abstract: We highlight current glycovaccines in the clinic and derive principles for the construction of the next generation of synthetically defined glycoconjugate vaccines.

Cited by 138 publications

References 117 publications

Defined Conjugation of Glycans to the Lysines of CRM197 Guided by their Reactivity Mapping

Defined Conjugation of Glycans to the Lysines of CRM197 Guided by their Reactivity Mapping

Two‐Step Functionalization of Oligosaccharides Using Glycosyl Iodide and Trimethylene Oxide and Its Applications to Multivalent Glycoconjugates

From Immunologically Archaic to Neoteric Glycovaccines

Contact Info

Product

Resources

About

Defined Conjugation of Glycans to the Lysines of CRM₁₉₇ Guided by their Reactivity Mapping

Defined Conjugation of Glycans to the Lysines of CRM₁₉₇ Guided by their Reactivity Mapping