Synthetic Oligomers Mimicking Capsular Polysaccharide Diheteroglycan are Potential Vaccine Candidates against Encapsulated Enterococcal Infections
| Autor: | Cecilia Martini, Dmitry A. Argunov, Nikolay E. Nifantiev, Riccardo Torelli, G. A. Van Der Marel, Jeroen D. C. Codée, Ermioni Kalfopoulou, Vadim B. Krylov, Maurizio Sanguinetti, Jacopo Enotarpi, Diana Laverde, Felipe Romero-Saavedra, Johannes Huebner |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
synthetic carbohydrate Glycoconjugate 030106 microbiology Polysaccharide Virulence factor Enterococcus faecalis Settore MED/07 - MICROBIOLOGIA E MICROBIOLOGIA CLINICA Microbiology 03 medical and health sciences vaccine Monosaccharide opsonophagocytic assay chemistry.chemical_classification biology biology.organism_classification In vitro capsular polysaccharide 030104 developmental biology Infectious Diseases chemistry diheteroglycan Polyclonal antibodies biology.protein Antibody |
| Zdroj: | ACS Infectious Diseases, 6(7), 1816-1826 |
| Popis: | Infections caused by Enterococcus spp., are a major concern in the clinical setting. In Enterococcus faecalis, the capsular polysaccharide diheteroglycan (DHG), composed of ß-D-galactofuranose-(1→3)-ß-D-glucopyranose repeats, has been described as an important virulence factor and as a potential vaccine candidate against encapsulated strains. Synthetic structures emulating immunogenic polysaccharides present many advantages over native polysaccharides for vaccine development. In this work, we described the synthesis of a library of DHG oligomers, differing in length and order of the monosaccharide constituents. Using suitably protected thioglycoside building blocks, oligosaccharides up to the 8-mer in length built up from either Galf-Glcp or Glcp-Galf dimers were generated and we evaluated their immunoreactivity with antibodies raised against DHG. After the screening, we selected two octasaccharides, having either a galactofuranose or glucopyranose terminus, which were conjugated to a carrier protein for the production of polyclonal antibodies. Resulting antibodies were specific towards the synthetic structures and mediated in-vitro opsonophagocytic killing of different encapsulated E. feacalis strains. The evaluated structures are the first synthetic structures described to elicit antibodies that target encapsulated E. faecalis strains, and are, therefore, promising candidates for the development of a well-defined enterococcal glycoconjugate vaccine. |
| Databáze: | OpenAIRE |
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