Potential targets for next generation antimicrobial glycoconjugate vaccines

Micoli, Francesca; Costantino, Paolo; Adamo, Roberto

doi:10.1093/femsre/fuy011

Cited by 135 publications

(109 citation statements)

References 417 publications

(406 reference statements)

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“…Pathogenic bacteria surface carbohydrates, either capsular polysaccharides (CPSs) when bacteria produce a capsule, cell wall-associated glycans in Gram-positive bacteria or lipopolysaccharides (LPSs) in Gram-negative bacteria are targets of choice for the development of glycoconjugate vaccines [107,108]. Various strategies have been proposed to access the relevant immunogenic oligosaccharides that could elicit an immune response and therefore be used in the composition of glycovaccines: extraction from natural sources, chemical synthesis (which remains the most used approach for the development of glycoconjugate vaccines in general), chemo-enzymatic synthesis and in vivo production by whole-cell biocatalysts.…”

Section: Targeting Bacterial Polysaccharidesmentioning

confidence: 99%

Harnessing glycoenzyme engineering for synthesis of bioactive oligosaccharides

et al. 2019

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Combined with chemical synthesis, the use of glycoenzyme biocatalysts has shown great synthetic potential over recent decades owing to their remarkable versatility in terms of substrates and regio- and stereoselectivity that allow structurally controlled synthesis of carbohydrates and glycoconjugates. Nonetheless, the lack of appropriate enzymatic tools with requisite properties in the natural diversity has hampered extensive exploration of enzyme-based synthetic routes to access relevant bioactive oligosaccharides, such as cell-surface glycans or prebiotics. With the remarkable progress in enzyme engineering, it has become possible to improve catalytic efficiency and physico-chemical properties of enzymes but also considerably extend the repertoire of accessible catalytic reactions and tailor novel substrate specificities. In this review, we intend to give a brief overview of the advantageous use of engineered glycoenzymes, sometimes in combination with chemical steps, for the synthesis of natural bioactive oligosaccharides or their precursors. The focus will be on examples resulting from the three main classes of glycoenzymes specialized in carbohydrate synthesis: glycosyltransferases, glycoside hydrolases and glycoside phosphorylases.

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Section: Targeting Bacterial Polysaccharidesmentioning

confidence: 99%

Harnessing glycoenzyme engineering for synthesis of bioactive oligosaccharides

et al. 2019

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“…As shown in Table 1, five carrier proteins (TT, Tetanus Toxoid; DT, Diphtheria Toxoid; CRM 197 , Cross Reacting Material 197; NTHi PD, non typeable H. influenzae protein D; OMPC, outer membrane protein complex) have been used for all licensed conjugate vaccines. 1 The toxoids DT and TT are obtained from the respective toxins by chemical detoxification with formaldehyde, while CRM 197 is a nontoxic mutant of diphtheria toxin isolated from the supernatant of Corynebacterium diphtheriae C7(b197) tox(À) strain bacterial growths or produced recombinantly in E. coli. Also NTHi PD is expressed in E. coli as recombinant protein.…”

Section: Protein Selectionmentioning

confidence: 99%

“…The biosynthesized bacterial oligosaccharides vary from O-antigens (Salmonella enterica, Shigella spp, E. Coli LPS) or capsular polysaccharides (S. aureus serotype 5 or 8 CPS and S. pneumoniae). 1 Typically, these conjugates are characterized by medium length heterogeneous oligosaccharides linked to one or two tags genetically inserted in the protein carrier (Fig. 4B).…”

Section: Different Types Of Site-selective Glycoconjugates Currentlymentioning

confidence: 99%

“…Among these, the structurally unique carbohydrates coating the surface of bacteria have become an optimal target for vaccine development. 1 Since the 1970s, it has been evident that the purified capsular polysaccharide from Streptococcus pneumoniae, Haemophilus influenzae type b (Hib) and…”

Section: Introductionmentioning

confidence: 99%

“…Following the success of capsular polysaccharide derived vaccines, the practise of protein conjugation has been extented to other classes of carbohydrates, including O-antigens, exopolysaccharides and teichoic acids. 1 Furthermore, emergence of bacterial species resistant to antibiotic treatment, as stressed out by recent WHO and CDC reports, is generating a call for novel, improved, fast acting vaccines. 1 While the commercially available vaccines (Table 1) were obtained through isolation of the polysaccharides from pathogens and were developed primarily based on empiric evidence, in the last twenty years there has been a rapid evolution in the approaches to obtain more defined carbohydrate antigens of higher purity.…”

Section: Introductionmentioning

confidence: 99%

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Antimicrobial glycoconjugate vaccines: an overview of classic and modern approaches for protein modification

Berti

Adamo

2018

Chem. Soc. Rev.

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Glycoconjugate vaccines obtained by chemical linkage of a carbohydrate antigen to a protein are part of routine vaccinations in many countries. Licensed antimicrobial glycan-protein conjugate vaccines are obtained by random conjugation of native or sized polysaccharides to lysine, aspartic or glutamic amino acid residues that are generally abundantly exposed on the protein surface. In the last few years, the structural approaches for the definition of the polysaccharide portion (epitope) responsible for the immunological activity has shown potential to aid a deeper understanding of the mode of action of glycoconjugates and to lead to the rational design of more efficacious and safer vaccines. The combination of technologies to obtain more defined carbohydrate antigens of higher purity and novel approaches for protein modification has a fundamental role. In particular, methods for site selective glycoconjugation like chemical or enzymatic modification of specific amino acid residues, incorporation of unnatural amino acids and glycoengineering, are rapidly evolving. Here we discuss the state of the art of protein engineering with carbohydrates to obtain glycococonjugates vaccines and future perspectives. Key learning points(a) The covalent linkage with proteins is fundamental to transform carbohydrates, which are per se T-cell independent antigens, in immunogens capable of evoking a long-lasting T-cell memory response. (b) Principal strategies for conjugation of bacterial polysaccharides with the protein carrier used in licensed glycoconjugate vaccines. (c) Modern methods for site selective glycoconjugation comprise chemical or enzymatic modification of specific amino acid residues, incorporation of unnatural amino acids and glycoengineering. (d) Importance of the definition of the polysaccharide portion (epitope) responsible for the immunological activity in the design of glycoconjugate vaccines.(e) How information from structural studies, strategies for carbohydrate production and protein modification can be combined in order to maximize the immunological activity of glycoconjugate vaccines.Chem. Soc. Rev., 2018, 47, 9015--9025 | 9017 Fig. 3 Approaches for selective glycoconjugation. CuAAC = cupper(II) catalyzed azide alkyne cycloaddition; SPAAC = strain promoted azide alkyne cycloaddition. SPAAC could deliver other isomers in addition to the depicted products. Tutorial ReviewChem Soc Rev

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Carbohydrate‐Based Therapeutics

2023

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Yaşam bilimlerinde karbohidratların önemi giderek artmaktadır. Karbohidratlar çok farklı biyolojik rollere sahiptir. Bu rollerden bir tanesi de onların tedavideki etkinlikleridir. Karbohidrat bazlı terapötikler, enflamatuar hastalıklar ve anti-trombotik tedavilerden yara iyileşmesine kadar değişen kardiyovasküler ve hematolojik hastalıkların tedavisinde kullanılmaktadır. Heparin, en yaygın bilinen karbohidrat bazlı ilaçtır. Karbohidrat bazlı terapötikler; polisakkarit ve oligosakarit içerikli anti-enflamatuarlar, antikoagülan ve antitrombotik ajanları, doğal ve sentetik kaynakları içermektedir. Bu bileşiklerin bazıları, artritik ve anti-HIV aktiviteler gösteren biyolojik etkilere sahiptir. Son yıllarda hem doğal hem de sentetik monosakkaritler, in vivo anti-kardiyoprotektif ve enflamatuar özellikleri açısından araştırılmaya başlanılmıştır. Bu derlemenin amacı karbohidrat bazlı terapotiklerin, hastalıkların tedavisindeki önemini vurgulamaktır.

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Potential targets for next generation antimicrobial glycoconjugate vaccines

Cited by 135 publications

References 417 publications

Harnessing glycoenzyme engineering for synthesis of bioactive oligosaccharides

Harnessing glycoenzyme engineering for synthesis of bioactive oligosaccharides

Antimicrobial glycoconjugate vaccines: an overview of classic and modern approaches for protein modification

Carbohydrate‐Based Therapeutics

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