Show legend Show as text

Structure type: homopolymer
Trivial name: repeating unit of capsular polysaccharide
Compound class: K-antigen, CPS
Contained glycoepitopes: IEDB_1330666,IEDB_1330667,IEDB_1330668,IEDB_1330669,IEDB_1330670,IEDB_1330671,IEDB_149552

• Article ID: 3364
  Nikolaev AV, Botvinko IV, Ross AJ "Natural phosphoglycans containing glycosyl phosphate units: structural diversity and chemical synthesis" - Carbohydrate Research 342(3-4) (2007) 297-344
  

  An anomeric phosphodiester linkage formed by a glycosyl phosphate unit and a hydroxyl group of another monosaccharide is found in many glycopolymers of the outer membrane in bacteria (e.g., capsular polysaccharides and lipopolysaccharides), yeasts and protozoa. The polymers (phosphoglycans) composed of glycosyl phosphate (or oligoglycosyl phosphate) repeating units could be chemically classified as poly(glycosyl phosphates). Their importance as immunologically active components of the cell wall and/or capsule of numerous microorganisms upholds the need to develop routes for the chemical preparation of these biopolymers. In this paper, we (1) present a review of the primary structures (known to date) of natural phosphoglycans from various sources, which contain glycosyl phosphate units, and (2) discuss different approaches and recent achievements in the synthesis of glycosyl phosphosaccharides and poly(glycosyl phosphates).

  synthesis, structure, polysaccharides, Phosphoglycans, Anomeric phosphodiesters

  NCBI PubMed ID: 17092493
  Publication DOI: 10.1016/j.carres.2006.10.006
  Journal NLM ID: 0043535
  Publisher: Elsevier
  Correspondence: a.v.nikolaev@dundee.ac.uk
  Institutions: College of Life Sciences, Division of Biological Chemistry and Molecular Microbiology, University of Dundee, Dundee DD1 5EH, UK.
  
   
  
  Neisseria meningitidis A
  CSDB ID 21767 (all data & tools)
• Article ID: 3583
  Filatova MP, Kotel'nikova OV, Chibiskova OV, Lakhtina OE, Nesmeyanov VA, Alliluev AP, Koroeva DO, Titova MA, Volkova TD, Vol'pina OM, Ivanov VT "Synthesis and Biological Properties of Polysaccharide-Peptide Conjugates as Potential Antigens for a Vaccine against Meningococci of Serogroups A and B" - Russian Journal of Bioorganic Chemistry 34(5) (2008) 570-638
  

  A new approach to the development of a vaccine against meningococci of serogroups A and B was proposed. It involves the synthesis of conjugates of high-molecular capsule polysaccharides of the serogroup A meningococcus (PsA) with earlier synthesized protective fragments of membrane proteins from serogroup B meningococci. The conjugates were synthesized using a method that consists of the generation of aldehyde groups by oxidizing free vicinal hydroxyl groups of PsA and subsequent reaction of these groups with amino groups of the peptide. The reaction proceeds with the intermediate formation of the Schiff base, which is reduced to the stable secondary amine. The main parameters of the reaction were optimized in the synthesis of a PsA conjugate with a model peptide and methods of their characterization were developed. The reproducibility and efficiency of the synthetic procedure were demonstrated by the example of synthesis of PsA conjugates with fragments of protein PorA from the outer membrane of the serogroup B meningococcus. It was shown that, when administered without adjuvant, a conjugate of PsA with a protective peptide, which represents an exposed conserved fragment 306-332 of protein PorA, stimulates the formation of antibodies to the peptide and polysaccharide moieties of the molecule and is also capable of decreasing the degree of bacteremia in animals infected with serogroup A and serogroup B meningococci. The approach can be applied to the development of a complex vaccine for serogroup A and serogroup B meningococci.

  Neisseria meningitidis, immunogenicity, conjugates, capsule polysaccharide, synthetic peptides, protectivity

  NCBI PubMed ID: 19060937
  Journal NLM ID: 9420101
  Publisher: Springer Science and Business Media
  Correspondence: filatova07@mail.ru
  Institutions: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences,ul. Miklukho-Maklaya 16/10, Moscow, 117997 Russia,Research Institute of General and Clinical Pathology, Russian University of Peoples’ Friendship, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, Moscow, 117997 Russia,Research Institute of General and Clinical Pathology, Russian University of Peoples’ Friendship
  Methods: serological methods
  
   
  
  Neisseria meningitidis A
  CSDB ID 23475 (all data & tools)
• Article ID: 6024
  Adegbite A, McCarthy PC "Recent and Future Advances in the Chemoenzymatic Synthesis of Homogeneous Glycans for Bacterial Glycoconjugate Vaccine Development" - Vaccines 9(9) (2021) 1021
  

  Vaccines are important in preventing disease outbreaks and controlling the spread of disease in a population. A variety of vaccines exist, including subunit, recombinant, and conjugate vaccines. Glycoconjugate vaccines have been an important tool to fight against diseases caused by a number of bacteria. Glycoconjugate vaccines are often heterogeneous. Vaccines of the future are becoming more rationally designed to have a defined oligosaccharide chain length and position of conjugation. Homogenous vaccines could play an important role in assessing the relationship between vaccine structure and immune response. This review focuses on recent advances in the chemoenzymatic production of defined bacterial oligosaccharides for vaccine development with a focus on Neisseria meningitidis and selected WHO-prioritized antibacterial resistant-pathogens. We also provide some perspective on future advances in the chemoenzymatic synthesis of well-defined oligosaccharides.

  synthesis, glycoconjugate vaccines, chemoenzymatic synthesis, bacterial pathogens

  NCBI PubMed ID: 34579258
  Publication DOI: 10.3390/vaccines9091021
  Journal NLM ID: 101629355
  Publisher: Basel, Switzerland: MDPI AG
  Correspondence: Pumtiwitt.McCarthy@morgan.edu
  Institutions: Department of Chemistry, Morgan State University, Baltimore, MD, USA, Bioenvironmental Sciences Program, Morgan State University, Baltimore, MD, USA
  
   
  
  Neisseria meningitidis A
  CSDB ID 10983 (all data & tools)

Show legend Show as text

Structure type: homopolymer
Compound class: CPS
Contained glycoepitopes: IEDB_1330666,IEDB_1330667,IEDB_1330668,IEDB_1330669,IEDB_1330670,IEDB_1330671,IEDB_149552

• Article ID: 3688
  Foschiatti M, Hearshaw M, Cescutti P, Ravenscroft N, Rizzo R "Conformational studies of the capsular polysaccharide produced by Neisseria meningitidis group A" - Carbohydrate Research 344(7) (2009) 940-943
  

  The effect of different cations on the conformational and morphological properties of the capsular polysaccharide produced by Neisseria meningitidis group A was investigated. Circular dichroism studies showed that the presence of Na(+), NH4+ or Ca(2+) ions induced different local conformations of the polysaccharide chain through interactions with the phosphodiester group bridging the saccharide residues in the polymer chain. Atomic force microscopy experiments confirmed that the morphology of the polysaccharide chains was different depending on the nature of the counterion. Ammonium ions were associated with the presence of single polymer chains in an elongated conformation, whereas sodium ions favored the folding of the chains into a globular conformation. The addition of calcium ions produced the aggregation of a limited number of globular polysaccharide chains to form a 'toroidal-like' structure

  conformation, structure, Neisseria meningitidis, capsular polysaccharide, vaccines, atomic force microscopy

  NCBI PubMed ID: 19306991
  Journal NLM ID: 0043535
  Publisher: Elsevier
  Correspondence: rizor@units.it (R.Rizzo)
  Institutions: Department of Life Sciences, University of Trieste, Bldg C11, Via Licio Giorgieri 1, 34127 Trieste, Italy
  Methods: light scattering, CD, atomic force microscopy
  
   
  
  Neisseria meningitidis A
  CSDB ID 23697 (all data & tools)

Show legend Show as text

Structure type: homopolymer
Compound class: CPS
Contained glycoepitopes: IEDB_1330666,IEDB_1330667,IEDB_1330668,IEDB_1330669,IEDB_1330670,IEDB_1330671,IEDB_149552

• 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: 26169742
  Publication DOI: 10.1007/978-1-4939-2874-3_12
  Journal NLM ID: 9214969
  Publisher: Springer
  Correspondence: francesco.x.berti@gsk.com
  Institutions: Research, GSK Vaccines, Via Fiorentina 1, 53100, Siena, Italy
  
   
  
  Neisseria meningitidis A
  CSDB ID 11087 (all data & tools)
• Article ID: 5447
  Hlozek J, Ravenscroft N, Kuttel MM "Modeling the conformations of Neisseria meningitidis serogroup a CPS and a carba-analogue: Implications for vaccine development" - Carbohydrate Research 486 (2019) 107838
  

  Neisseria meningitidis is a major cause of bacterial meningitis worldwide, especially in Africa. The capsular polysaccharide is the main virulence factor and the target antigen for polysaccharide- and conjugate vaccines. Three tetravalent conjugate vaccines against serogroups A, C, Y and W have been licensed and the monovalent MenAfriVac was introduced to address the high burden of serogroup A disease in the Meningitis Belt of sub-Saharan Africa. Three of these four vaccines are lyophilized due to the instability of the serogroup A antigen (MenA) in aqueous solution, resulting in a two vial presentation with concomitant additional costs for storage and distribution. Replacement of the saccharide ring oxygen with a methylene group is a promising approach to preparing a stable oligosaccharide MenA analogue (Carba-MenA) vaccine suitable for a liquid formulation. However, to be effective, Carba-MenA must elicit an immune response that is cross-reactive to the native MenA. Here we employ microsecond molecular dynamics simulations of ten repeats of MenA and Carba-MenA to establish that there are significant differences in the conformation and dynamics of these antigens in solution. Carba-MenA has a more random extended, conformation than MenA; MenA has a significant population of compact S-bend conformations that are absent in the analogue. We also find that the disaccharides are poor models of the conformational behaviour of longer chains. This information is relevant for the rational design of optimal analogues for conjugate vaccines.

  Neisseria meningitidis, capsular polysaccharide, molecular modeling, vaccine, serogroup A, Antigen conformation, Carba-analogue

  Publication DOI: 10.1016/j.carres.2019.107838
  Journal NLM ID: 0043535
  Publisher: Elsevier
  Correspondence: M.M. Kuttel
  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, molecular modeling, MD simulation, CHARMM program
  
   
  
  Neisseria meningitidis A
  CSDB ID 1028 (all data & tools)
• Article ID: 5763
  Fiebig T, Cramer JT, Bethe A, Baruch P, Curth U, Fuhring JI, Buettner FFR, Vogel U, Schubert M, Fedorov R, Muhlenhoff M "Structural and mechanistic basis of capsule O-acetylation in Neisseria meningitidis serogroup A" - Nature Communications 11(1) (2020) 4723
  

  O-Acetylation of the capsular polysaccharide (CPS) of Neisseria meningitidis serogroup A (NmA) is critical for the induction of functional immune responses, making this modification mandatory for CPS-based anti-NmA vaccines. Using comprehensive NMR studies, we demonstrate that O-acetylation stabilizes the labile anomeric phosphodiester-linkages of the NmA-CPS and occurs in position C3 and C4 of the N-acetylmannosamine units due to enzymatic transfer and non-enzymatic ester migration, respectively. To shed light on the enzymatic transfer mechanism, we solved the crystal structure of the capsule O-acetyltransferase CsaC in its apo and acceptor-bound form and of the CsaC-H228A mutant as trapped acetyl-enzyme adduct in complex with CoA. Together with the results of a comprehensive mutagenesis study, the reported structures explain the strict regioselectivity of CsaC and provide insight into the catalytic mechanism, which relies on an unexpected Gln-extension of a classical Ser-His-Asp triad, embedded in an alpha/beta-hydrolase fold.

  NMR, Neisseria meningitidis, capsular polysaccharide, O-acetylation, crystal structure, capsule, CPS, immune response, acetyltransferase

  NCBI PubMed ID: 32948778
  Publication DOI: 10.1038/s41467-020-18464-y
  Journal NLM ID: 101528555
  Publisher: London: Nature Publishing Group
  Correspondence: Fiebig.Timm@mh-hannover.de; Muehlenhoff.Martina@mh-hannover.de
  Institutions: Institute of Clinical Biochemistry, Hannover Medical School, Hannover, Germany, Institute for Virology, Hannover Medical School, Hannover, Germany, Institute for Biophysical Chemistry, Hannover Medical School, Hannover, Germany, Fraunhofer International Consortium for Anti-Infective Research (iCAIR), Hannover, Germany, Institute for Hygiene and Microbiology, University of Wurzburg, Wurzburg, Germany, Department of Biosciences, University of Salzburg, Salzburg, Austria
  Methods: 13C NMR, 1H NMR, NMR-2D, 31P NMR, crystallography, cloning, bioinformatic analysis, LC-ESI-MS, O-acetyltransferase assay
  
   
  
  Neisseria meningitidis A
  CSDB ID 32096 (all data & tools)
• 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: 34388671
  Publication DOI: 10.1016/j.jpba.2021.114302
  Journal NLM ID: 8309336
  Publisher: 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
  
   
  
  Neisseria meningitidis A
  CSDB ID 7867 (all data & tools)

Show legend Show as text

Structure type: homopolymer
Compound class: CPS
Contained glycoepitopes: IEDB_1330666,IEDB_1330667,IEDB_1330668,IEDB_1330669,IEDB_1330670,IEDB_1330671,IEDB_149552

• 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: 28501716
  Publication DOI: 10.1016/j.carres.2017.05.004
  Journal NLM ID: 0043535
  Publisher: 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
  
   
  
  Neisseria meningitidis A
  CSDB ID 11926 (all data & tools)
• 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: 29865239
  Publication DOI: 10.3390/molecules23061340
  Journal NLM ID: 100964009
  Publisher: Basel, Switzerland: MDPI
  Correspondence: rino.x.rappuoli@gsk.com
  Institutions: External R&D, GSK Vaccines, 53100 Siena, Italy
  
   
  
  Neisseria meningitidis A
  CSDB ID 12871 (all data & tools)
• Article ID: 5134
  Calloni I, Unione L, Jimenez-Oses G, Corzana F, Del Bino L, Corrado A, Pitirollo O, Colombo C, Lay L, Adamo R, Jiménez-Barbero J "The Conformation of the Mannopyranosyl Phosphate Repeating Unit of the Capsular Polysaccharide of Neisseria meningitidis Serogroup A and Its Carba-Mimetic" - European Journal of Organic Chemistry 33 (2018) 4548-4555
  

  Neisseria meningitidis serogroup A (MenA) is an aerobic diplococcal Gram-negative bacterium responsible for epidemic meningitis disease. Its capsular polysaccharide (CPS) has been identified as the primary virulence factor of MenA. This polysaccharide suffers from chemical lability in water. Thus, the design and synthesis of novel and hydrolytically stable structural analogues of MenA CPS may provide additional tools for the development of therapies against this disease. In this context, the structural features of the natural phosphorylated monomer have been analyzed and compared to those of its carba-analogue, where the endocyclic oxygen has been replaced by a methylene moiety. The lowest energy geometries of the different molecules have been calculated using a combination of quantum mechanical techniques and molecular dynamics simulations. The predicted results have been compared and validated using NMR experiments. The results indicate that the more stable designed glycomimetics may adopt the conformation adopted by the natural monomer, although they display a wider flexibility around the torsional degrees of freedom.

  structure elucidation, conformation analysis, chemical, natural products, synthesis design, Glycomimetics, LAB

  NCBI PubMed ID: 30443159
  Publication DOI: 10.1002/ejoc.201801003
  Journal NLM ID: 9805750
  Publisher: Wiley-VCH
  Correspondence: jjbarbero@cicbiogune.es
  Institutions: Chemical Glycobiology Lab CIC bioGUNE Bizkaia Technology Park, Derio, Spain, Department of Organic Chemistry II Faculty of Science and Technology University of the Basque Country, EHU-UPV Leioa Spain, Atlas Molecular Pharma Bizkaia Technology Park, Derio, Spain, Departamento de Quimica Universidad de la Rioja Centro Cientifico Tecnologico Spain, Glycobiology Lab GSK Via Fiorentina 10 Siena Italy, Department of Chemistry and ISTM_CNR University of Milan Via Golgi 19 20133 Milan Italy, Basque Foundation for Science (IKERBASQUE), Bilbao, Spain
  Methods: NMR, conformation analysis, chemical synthesis, MD simulations, computational methods
  
   
  
  Neisseria meningitidis A
  CSDB ID 12877 (all data & tools)
• 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: 33388123
  Publication DOI: 10.1016/j.ddtec.2020.08.002
  Journal NLM ID: 101235076
  Publisher: 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
  
   
  
  Neisseria meningitidis A
  CSDB ID 32108 (all data & tools)
• Article ID: 6211
  Del Bino L, Osterlid KE, Wu DY, Nonne F, Romano MR, Codée J, Adamo R "Synthetic Glycans to Improve Current Glycoconjugate Vaccines and Fight Antimicrobial Resistance" - Chemical Reviews 122(20) (2022) 15672-15716
  

  Antimicrobial resistance (AMR) is emerging as the next potential pandemic. Different microorganisms, including the bacteria Acinetobacter baumannii, Clostridioides difficile, Escherichia coli, Enterococcus faecium, Klebsiella pneumoniae, Neisseria gonorrhoeae, Pseudomonas aeruginosa, non-typhoidal Salmonella, and Staphylococcus aureus, and the fungus Candida auris, have been identified by the WHO and CDC as urgent or serious AMR threats. Others, such as group A and B Streptococci, are classified as concerning threats. Glycoconjugate vaccines have been demonstrated to be an efficacious and cost-effective measure to combat infections against Haemophilus influenzae, Neisseria meningitis, Streptococcus pneumoniae, and, more recently, Salmonella typhi. Recent times have seen enormous progress in methodologies for the assembly of complex glycans and glycoconjugates, with developments in synthetic, chemoenzymatic, and glycoengineering methodologies. This review analyzes the advancement of glycoconjugate vaccines based on synthetic carbohydrates to improve existing vaccines and identify novel candidates to combat AMR. Through this literature survey we built an overview of structure-immunogenicity relationships from available data and identify gaps and areas for further research to better exploit the peculiar role of carbohydrates as vaccine targets and create the next generation of synthetic carbohydrate-based vaccines.

  carbohydrates, glycan, glycoconjugate vaccine

  NCBI PubMed ID: 35608633
  Publication DOI: 10.1021/acs.chemrev.2c00021
  Journal NLM ID: 2985134R
  Publisher: Chem Rev
  Correspondence: J. Codée ; R. Adamo
  Institutions: GSK, R&D, 53100 Siena, Italy, Leiden Institute of Chemistry, Leiden University, 2300 RA Leiden, The Netherlands
  
   
  
  Neisseria meningitidis A
  CSDB ID 20872 (all data & tools)
• 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: 36234967
  Publication DOI: 10.3390/molecules27196432
  Journal NLM ID: 100964009
  Publisher: 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
  
   
  
  Neisseria meningitidis A
  CSDB ID 8813 (all data & tools)

Show legend Show as text

Structure type: homopolymer
Compound class: CPS
Contained glycoepitopes: IEDB_1330666,IEDB_1330667,IEDB_1330668,IEDB_1330669,IEDB_1330670,IEDB_1330671,IEDB_149552

• 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: 29940397
  Publication DOI: 10.1016/j.carres.2018.06.007
  Journal NLM ID: 0043535
  Publisher: 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
  
   
  
  Neisseria meningitidis A
  CSDB ID 12913 (all data & tools)

Show legend Show as text

Structure type: homopolymer ; n=18
Trivial name: type A polysaccharide
Compound class: CPS
Contained glycoepitopes: IEDB_1330666,IEDB_1330667,IEDB_1330668,IEDB_1330669,IEDB_1330670,IEDB_1330671,IEDB_149552

• 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: 33721150
  Publication DOI: 10.1007/s10719-021-09991-x
  Journal NLM ID: 8603310
  Publisher: 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
  
   
  
  Neisseria meningitidis A
  CSDB ID 10892 (all data & tools)