Synthetic Oligomers Mimicking Capsular Polysaccharide Diheteroglycan are Potential Vaccine Candidates against Encapsulated Enterococcal Infections

D. Laverde, F. Romero-Saavedra, D. A. Argunov, J. Enotarpi, V. B. Krylov, E. Kalfopoulou, C. Martini, R. Torelli, G. A. Van Der Marel, M. Sanguinetti, J. D.C. Codeé, N. E. Nifantiev, J. Huebner

Research output: Contribution to journalArticlepeer-review

Abstract

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 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. The resulting antibodies were specific toward the synthetic structures and mediated in vitro opsonophagocytic killing of different encapsulated E. feacalis strains. The evaluated oligosaccharides 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.

Original languageEnglish
Pages (from-to)1816-1826
Number of pages11
JournalACS Infectious Diseases
Volume6
Issue number7
DOIs
Publication statusPublished - Jul 10 2020

Keywords

  • capsular polysaccharide
  • diheteroglycan
  • Enterococcus faecalis
  • opsonophagocytic assay
  • synthetic carbohydrate
  • vaccine

ASJC Scopus subject areas

  • Infectious Diseases

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