Taxonomic group: bacteria / Proteobacteria
(Phylum: Proteobacteria)
Host organism: Homo sapiens
Associated disease: meningitis [ICD11:
1D01 
];
infection due to Neisseria meningitidis [ICD11:
XN1DV ]
Publication DOI: 10.1016/j.carres.2019.107838Journal NLM ID: 0043535Publisher: Elsevier
Correspondence: M.M. Kuttel <mkuttel
cs.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
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
Structure type: homopolymer
Location inside paper: fig.1(a)
Compound class: CPS
Contained glycoepitopes: IEDB_1330666,IEDB_1330667,IEDB_1330668,IEDB_1330669,IEDB_1330670,IEDB_1330671,IEDB_149549,IEDB_149550,IEDB_149551,IEDB_149552
Methods: conformation analysis, molecular modeling, MD simulation, CHARMM computations
3D data: molecular modeling
NCBI Taxonomy refs (TaxIDs): 65699
Show glycosyltransferases
There is only one chemically distinct structure:
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