Found 4 structures.
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1. Compound ID: 2697
Structure type: polymer chemical repeating unit
Trivial name: type Y polysaccharide
Compound class: CPS
Contained glycoepitopes: IEDB_136794,IEDB_142488,IEDB_144998,IEDB_146100,IEDB_146664,IEDB_148489,IEDB_149174,IEDB_158547,IEDB_158561,IEDB_983931,SB_170,SB_171,SB_172,SB_192,SB_84
The structure is contained in the following publication(s):
- Article ID: 926
Lemercinier X, Jones C "Full 1H NMR assignment and detailed O-acetylation patterns of capsular polysaccharides from Neisseria meningitidis used in vaccine production" -
Carbohydrate Research 296(1-4) (1996) 83-96
We report esssentially complete 1H NMR assignments for the capsular polysaccharides from Neisseria meningitidis serotypes A, C, W-135, and Y. These polysaccharides are components of current polysaccharide vaccines against meningococcal infection and of the polysaccharide-protein conjugate vaccines under development. From these NMR data the pattern of O-acetylation was determined. O-Acetylation of the W-135 polysaccharide is reporded for the first time. We also show that, for the Types C and W-135 polysaccharides, a migration of O-acetyl groups occurs during storage in solution, and demonstrate that high field 1H NMR represents a simple and sensititve method to define the O-acetylation pattern of individual batches of these polysaccharides.
NMR, structure, Neisseria meningitidis, Neisseria, capsular, polysaccharide, capsular polysaccharide, capsular polysaccharides, polysaccharides, O-acetylation, production, vaccine, assignment, 1H NMR, pattern
Publication DOI: 10.1016/S0008-6215(96)00253-4Journal NLM ID: 0043535Publisher: Elsevier
Correspondence: cjones@nibsc.ac.uk
Institutions: Laboratory for Molecular Structure, National Institute for Biological Standards and Control, South Mimms, UK
Methods: NMR-2D, NMR
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2. Compound ID: 12151
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/Variants 0/-+
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-6)-a-D-Glcp-(1-4)-a-Neup5Ac-(2-
/Variants 0/ is:
?%Ac-9)-
OR (exclusively)
?%Ac-7)- |
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Structure type: polymer chemical repeating unit
Compound class: CPS
Contained glycoepitopes: IEDB_136794,IEDB_142488,IEDB_144998,IEDB_146100,IEDB_146664,IEDB_148489,IEDB_149174,IEDB_158547,IEDB_158561,IEDB_983931,SB_170,SB_171,SB_172,SB_192,SB_84
The structure is contained in the following publication(s):
- Article ID: 4835
Berti F, Ravenscroft N "Characterization of Carbohydrate Vaccines by NMR Spectroscopy" -
Methods in Molecular Biology 1331 (2015) 189-209
Physicochemical techniques are a powerful tool for the structural characterization of carbohydrate-based vaccines. High-field Nuclear Magnetic Resonance (NMR) spectroscopy has been established as an extremely useful and robust method for tracking the industrial manufacturing process of these vaccines from polysaccharide bulk antigen through to the final formulation. Here, we describe the use of proton NMR for structural identity and conformity testing of carbohydrate-based vaccines.
carbohydrates, capsular polysaccharide, antigens, nuclear magnetic resonance spectroscopy, vaccines
NCBI PubMed ID: 26169742Publication DOI: 10.1007/978-1-4939-2874-3_12Journal NLM ID: 9214969Publisher: Springer
Correspondence: francesco.x.berti@gsk.com
Institutions: Research, GSK Vaccines, Via Fiorentina 1, 53100, Siena, Italy
- Article ID: 5015
Kuttel MM, Timol Z, Ravenscroft N "Cross-protection in Neisseria meningitidis serogroups Y and W polysaccharides: A comparative conformational analysis" -
Carbohydrate Research (2017) 40-47
The capsular polysaccharide is the main virulence factor in meningococcus. The capsular polysaccharides for meningococcal serogroups Y and W are almost identical polymers of hexose-sialic acid, suggesting the possibility of cross-protection between group Y and W vaccines. However, early studies indicated that they elicit different levels of cross-protection. Here we explore the conformations of the meningococcal Y and W polysaccharides with molecular dynamics simulations of three repeating unit oligosaccharide strands. We find differences in Y and W antigen conformation: the Y polysaccharide has a single dominant conformation, whereas W exhibits a family of conformations including the Y conformation. This result is supported by our NMR NOESY analysis, which indicates key close contacts for W that are not present in Y. These conformational differences provide an explanation for the different levels of cross-protection measured for the Y and W monovalent vaccines and the high group W responses observed in HibMenCY-TT vaccinees.
molecular modelling, Meningococcus, Neisseria meningitidis, capsular polysaccharide, carbohydrate antigens, cross-protection, molecular dynamics simulation
NCBI PubMed ID: 28501716Publication DOI: 10.1016/j.carres.2017.05.004Journal NLM ID: 0043535Publisher: Elsevier
Correspondence: mkuttel@cs.uct.ac.za
Institutions: Department of Computer Science, University of Cape Town, Cape Town, 7701, South Africa
Methods: 13C NMR, 1H NMR, NMR-2D, conformation analysis, MD simulations, de-O-acetylation
- Article ID: 5128
Berti F, De Ricco R, Rappuoli R "Role of O-Acetylation in the Immunogenicity of Bacterial Polysaccharide Vaccines" -
Molecules 23(6) (2018) pii E1340
The incidence of infectious diseases caused by several bacterial pathogens such as Haemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis, has been dramatically reduced over the last 25 years through the use of glycoconjugate vaccines. The structures of the bacterial capsular polysaccharide (CPS) antigens, extracted and purified from microbial cultures and obtained with very high purity, show that many of them are decorated by O-acetyl groups. While these groups are often considered important for the structural identity of the polysaccharides, they play a major role in the functional immune response to some vaccines such as meningococcal serogroup A and Salmonella typhi Vi, but do not seem to be important for many others, such as meningococcal serogroups C, W, Y, and type III Group B Streptococcus. This review discusses the O-acetylation status of CPSs and its role in the immunological responses of these antigens.
O-acetylation, Bacterial polysaccharide, conjugate vaccines, Bacterial Vaccines, carbohydrate antigens
NCBI PubMed ID: 29865239Publication DOI: 10.3390/molecules23061340Journal NLM ID: 100964009Publisher: Basel, Switzerland: MDPI
Correspondence: rino.x.rappuoli@gsk.com
Institutions: External R&D, GSK Vaccines, 53100 Siena, Italy
- Article ID: 5161
Hlozek J, Kuttel MM, Ravenscroft N "Conformations of Neisseria meningitidis serogroup A and X polysaccharides: The effects of chain length and O-acetylation" -
Carbohydrate Research 465 (2018) 44-51
Neisseria meningitidis is a major cause of bacterial meningitis worldwide especially in Africa. The capsular polysaccharide (CPS) is the main virulence factor and the target antigen for polysaccharide and conjugate vaccines. The high burden of serogroup A disease in the Meningitis Belt of sub-Saharan Africa led to the introduction of MenAfriVac®, which has successfully reduced the number of cases of group A disease. However, several outbreaks caused by other serogroups have been reported, including those due to serogroup X. The capsular polysaccharides of serogroups A and X are both homopolymers of amino sugars (?-D-ManNAc and ?-D-GlcNAc) containing phosphodiester linkages at C-6 and C-4, respectively. The similarity of the primary structures of the two polysaccharides suggests that serogroup A vaccination may provide cross-protection against serogroup X disease. Molecular dynamics simulations of a series of serogroup A and X oligosaccharides reveal that the MenA CPS behaves as a flexible random coil which becomes less conformationally defined as the length increases, whereas serogroup X forms a more stable regular helical structure. The presence of the MenX helix is supported by NMR analysis; it has four residues per turn and becomes more stable as the chain length increases. Licensed MenA vaccines are largely O-acetylated at C-3: simulations show that these O-acetyl groups are highly solvent exposed and their presence favors more extended conformations compared to the more compact conformations of MenA without O-acetylation. These findings may have implications for the design of optimal conjugate vaccines.
Neisseria meningitidis, capsular polysaccharide, molecular modeling, Antigen conformation
NCBI PubMed ID: 29940397Publication DOI: 10.1016/j.carres.2018.06.007Journal NLM ID: 0043535Publisher: Elsevier
Correspondence: neil.ravenscroft@uct.ac.za
Institutions: Department of Chemistry, University of Cape Town, Rondebosch, 7701, South Africa, Department of Computer Science, University of Cape Town, Rondebosch, 7701, South Africa
Methods: conformation analysis, MD simulations, post-simulation analysis
- Article ID: 5774
Gomez-Redondo M, Arda A, Gimeno A, Jiménez-Barbero J "Bacterial polysaccharides: conformation, dynamics and molecular recognition by antibodies" -
Drug Discovery Today: Technologies (2020) 1-11
Bacterial infections are the cause of different severe health conditions and new therapies to combat these pathogens have been widely investigated. Carbohydrates, being complex structures covering the surface of bacteria, are considered relevant targets for antibody and vaccine development. The biological activities in pathogenesis of bacterial capsular polysaccharides and lipopolisaccharides and their unique structures have boosted the study of the minimal antigenic binding epitopes and the structural details of antibody-carbohydrate recognition. This review describes the most recent advances on the field, examining the structure, conformation and dynamics of relevant bacterial carbohydrates and their complexes with antibodies. The understanding of key factors governing the recognition process is fundamental for the progress toward the development of specific and efficient bacterial therapeutics.
conformation, structure, capsular polysaccharides, epitope, recognition, dynamics, binding, vaccine, bacterial infection
NCBI PubMed ID: 33388123Publication DOI: 10.1016/j.ddtec.2020.08.002Journal NLM ID: 101235076Publisher: Oxford: Elsevier
Institutions: CIC bioGUNE, Basque Research Technology Alliance, BRTA, Bizkaia Technology Park, Building 800, 48160 Derio, Spain, Ikerbasque, Basque Foundation for Science, 48009 Bilbao, Spain, Department Organic Chemistry II, Faculty of Science and technology, UPV-EHU, 48940 Leioa, Spain
- Article ID: 6032
Berti F "NMR characterization of a multi-valent conjugate vaccine against Neisseria meningitidis A, C, W, Y and Haemophilus influenzae b infections" -
Journal of Pharmaceutical and Biomedical Analysis 205 (2021) 114302
Physicochemical technologies are a powerful tool for the structural characterization of vaccine antigens both at bulk level as well as on the final formulation. High-field Nuclear Magnetic Resonance (NMR) spectroscopy has been found to be an extremely and robust tool for tracking the industrial process manufacturing of carbohydrate-based vaccines. I have applied NMR spectroscopy to the characterization of a penta-valent conjugate vaccine against Neisseria meninigitidis group A, C, W, Y (MenACWY) and Haemophilus influenzae type b (Hib) infections, constituted of capsule derived polysaccharide fragments independently conjugated to CRM197 protein carrier (CRM-MenA, CRM-MenC, CRM-MenW, CRM-MenY, CRM-Hib). 1H NMR has been used for the identity testing of the carbohydrate antigens and of the vaccine formulation. The application of NMR-based assays on multivalent conjugate vaccines looks to be a promising approach for identity and stability analyses useful for future vaccines development.
glycoconjugates, nuclear magnetic resonance spectroscopy, vaccines, Haemophilus influenzae type b, Bacterial Infections, Neisseria meningitidis serogroup A/C/W/Y
NCBI PubMed ID: 34388671Publication DOI: 10.1016/j.jpba.2021.114302Journal NLM ID: 8309336Publisher: London: Elsevier
Correspondence: francesco.x.berti@gsk.com
Institutions: GSK, Via Fiorentina 1, 53100 Siena, Italy
Methods: 13C NMR, 1H NMR, 31P NMR, vaccine formulations
- Article ID: 6096
Kuttel MM, Berti F, Ravenscroft N "Molecular modeling provides insights into the loading of sialic acid-containing antigens onto CRM 197: the role of chain flexibility in conjugation efficiency and glycoconjugate architecture" -
Glycoconjugate Journal 38(4) (2021) 411-419
Vaccination is the most cost-effective way to control disease caused by encapsulated bacteria; the capsular polysaccharide (CPS) is the primary virulence factor and vaccine target. Neisseria meningitidis (Nm) serogroups B, C, Y and W all contain sialic acid, a common surface feature of human pathogens. Two protein-based vaccines against serogroup B infection are available for human use while four tetravalent conjugate vaccines including serogroups C, W and Y have been licensed. The tetravalent Menveo® conjugate vaccine is well-defined: a simple monomeric structure of oligosaccharides terminally conjugated to amino groups of the carrier protein CRM197. However, not only is there a surprisingly low limit for antigen chain attachment to CRM197, but different serogroup saccharides have consistently different CRM197 loading, the reasons for which are unclear. Understanding this phenomenon is important for the long-term goal of controlling conjugation to prepare conjugate vaccines of optimal immunogenicity. Here we use molecular modeling to explore whether antigen flexibility can explain the varying antigen loading of the conjugates. Because flexibility is difficult to separate from other structural factors, we focus on sialic-acid containing CPS present in current glycoconjugate vaccines: serogroups NmC, NmW and NmY. Our simulations reveal a correlation between Nm antigen flexibility (NmW > NmC > NmY) and the number of chains attached to CRM197, suggesting that increased flexibility enables accommodation of additional chains on the protein surface. Further, in silico models of the glycoconjugates confirm the relatively large hydrodynamic size of the saccharide chains and indicate steric constraints to further conjugation.
Neisseria meningitidis, capsular polysaccharide, molecular modeling, Antigen conformation, conjugation efficiency, glycoconjugate structure
NCBI PubMed ID: 33721150Publication DOI: 10.1007/s10719-021-09991-xJournal NLM ID: 8603310Publisher: Kluwer Academic Publishers
Correspondence: neil.ravenscroft@uct.ac.za
Institutions: Department of Computer Science, University of Cape Town, 7701, Cape Town, South Africa, Technical Research & Development, GSK Vaccines S.r.l, Via Fiorentina 1, 53100, Siena, Italy, Department of Chemistry, University of Cape Town, 7701, Cape Town, South Africa
Methods: MD simulations, molecular modeling, CarbBuilder, CHARMM36
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3. Compound ID: 12227
Structure type: polymer chemical repeating unit
Compound class: CPS
Contained glycoepitopes: IEDB_136794,IEDB_142488,IEDB_144998,IEDB_146100,IEDB_146664,IEDB_148489,IEDB_149174,IEDB_158547,IEDB_158561,IEDB_983931,SB_170,SB_171,SB_172,SB_192,SB_84
The structure is contained in the following publication(s):
- Article ID: 4867
Tzeng YL, Thomas J, Stephens DS "Regulation of capsule in Neisseria meningitidis" -
Critical Reviews in Microbiology 42(5) (2016) 759-772
Neisseria meningitidis, a devastating pathogen exclusive to humans, expresses capsular polysaccharides that are the major meningococcal virulence determinants and the basis for successful meningococcal vaccines. With rare exceptions, the expression of capsule (serogroups A, B, C, W, X, Y) is required for systemic invasive meningococcal disease. Changes in capsule expression or structure (e.g. hypo- or hyper-encapsulation, capsule 'switching', acetylation) can influence immunologic diagnostic assays or lead to immune escape. The loss or down-regulation of capsule is also critical in meningococcal biology facilitating meningococcal attachment, microcolony formation and the carriage state at human mucosal surfaces. Encapsulated meningococci contain a cps locus with promoters located in an intergenic region between the biosynthesis and the conserved capsule transport operons. The cps intergenic region is transcriptionally regulated (and thus the amount of capsule expressed) by IS element insertion, by a two-component system, MisR/MisS and through sequence changes that result in post-transcriptional RNA thermoregulation. Reversible on-off phase variation of capsule expression is controlled by slipped strand mispairing of homo-polymeric tracts and by precise insertion and excision of IS elements (e.g. IS1301) in the biosynthesis operon. Capsule structure can be altered by phase-variable expression of capsular polymer modification enzymes or 'switched' through transformation and homologous recombination of different polymerases. Understanding the complex regulation of meningococcal capsule has important implications for meningococcal biology, pathogenesis, diagnostics, current and future vaccine development and vaccine strategies.
Neisseria meningitidis, capsular polysaccharide, Bacterial virulence regulation, capsule switching, meningococcal diseases
NCBI PubMed ID: 26089023Publication DOI: 10.3109/1040841X.2015.1022507Journal NLM ID: 8914274Publisher: CRC Press
Correspondence: dstep01@emory.edu
Institutions: Department of Medicine, Emory University School of Medicine, Woodruff Health Sciences Center, Atlanta, GA, USA
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4. Compound ID: 16287
Structure type: polymer chemical repeating unit
Compound class: CPS
Contained glycoepitopes: IEDB_136794,IEDB_142488,IEDB_144998,IEDB_146100,IEDB_146664,IEDB_148489,IEDB_149174,IEDB_158547,IEDB_158561,IEDB_983931,SB_170,SB_171,SB_172,SB_192,SB_84
The structure is contained in the following publication(s):
- Article ID: 6318
Srtefanetti G, Maclennan CA, Micoli F "Impact and Control of Sugar Size in Glycoconjugate Vaccines" -
Molecules 27(19) (2022) 6432
Glycoconjugate vaccines have contributed enormously to reducing and controlling encapsulated bacterial infections for over thirty years. Glycoconjugate vaccines are based on a carbohydrate antigen that is covalently linked to a carrier protein; this is necessary to cause T cell responses for optimal immunogenicity, and to protect young children. Many interdependent parameters affect the immunogenicity of glycoconjugate vaccines, including the size of the saccharide antigen. Here, we examine and discuss the impact of glycan chain length on the efficacy of glycoconjugate vaccines and report the methods employed to size polysaccharide antigens, while highlighting the underlying reaction mechanisms. A better understanding of the impact of key parameters on the immunogenicity of glycoconjugates is critical to developing a new generation of highly effective vaccines.
glycoconjugates, vaccine, immunogenicity, fragmentation of polysaccharides, sugar length
NCBI PubMed ID: 36234967Publication DOI: 10.3390/molecules27196432Journal NLM ID: 100964009Publisher: Basel, Switzerland: MDPI
Correspondence: G. Srtefanetti
Institutions: Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy, Enteric and Diarrheal Diseases, Global Health, Bill & Melinda Gates Foundation, 500 5th Ave. N, Seattle, WA 98109, USA, The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7DQ, UK, The Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK, GSK Vaccines Institute for Global Health, 53100 Siena, Italy
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