Leiden University Scholarly Publications

Persistent URL of this record https://hdl.handle.net/1887/3200734

In Collections

This item can be found in the following collections:

Laverde, D.; Romero-Saavedra, F.; Argunov, D.A.; Enotarpi, J.; Krylov, V.B.; Kalfopoulou, E.; ... ; Huebner, J. (2020)

Synthetic oligomers mimicking capsular polysaccharide diheteroglycan are potential vaccine candidates against encapsulated Enterococcal infections

Article / Letter to editor
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...Show moreInfections 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.Show less
All authors
Laverde, D.; Romero-Saavedra, F.; Argunov, D.A.; Enotarpi, J.; Krylov, V.B.; Kalfopoulou, E.; Martini, C.; Torelli, R.; Marel, G.A. van der; Sanguinetti, M.; Codée, J.D.C.; Nifantiev, N.E.; Huebner, J.
Date
2020-05-04
Journal
ACS Infectious Diseases
Volume
6
Issue
7
Pages
1816 - 1826
DOI
doi:10.1021/acsinfecdis.0c00063
Link
https://pubs.acs.org/doi/10.1021/acsinfecdis.0c00063