Conjugation of Different Immunogenic Enterococcal Vaccine Target Antigens Leads to Extended Strain Coverage

J Infect Dis. 2019 Oct 8;220(10):1589-1598. doi: 10.1093/infdis/jiz357.


Enterococci have emerged as important nosocomial pathogens due to their resistance to the most commonly used antibiotics. Alternative treatments or prevention options are aimed at polysaccharides and surface-related proteins that play important roles in pathogenesis. Previously, we have shown that 2 Enterococcus faecium proteins, the secreted antigen A and the peptidyl-prolyl cis-trans isomerase, as well as the Enterococcus faecalis polysaccharide diheteroglycan, are able to induce opsonic and cross-protective antibodies. Here, we evaluate the use of glycoconjugates consisting of these proteins and an enterococcal polysaccharide to develop a vaccine with broader strain coverage. Diheteroglycan was conjugated to these 2 enterococcal proteins. Rabbit sera raised against these glycoconjugates showed Immunoglobulin G titers against the corresponding conjugate, as well as against the respective protein and carbohydrate antigens. Effective opsonophagocytic killing for the 2 sera was observed against different E. faecalis and E. faecium strains. Enzyme-linked immunosorbent assays against whole bacterial cells showed immune recognition of 22 enterococcal strains by the sera. Moreover, the sera conferred protection against E. faecalis and E. faecium strains in a mouse infection model. Our results suggest that these glycoconjugates are promising candidates for vaccine formulations with a broader coverage against these nosocomial pathogens and that the evaluated proteins are potential carrier proteins.

Keywords: Enterococcus faecalis; Enterococcus faecium; Vaccine; capsular polysaccharide; carrier protein; diheteroglycan; enterococcal proteins; glycoconjugate; mouse infection model; opsonophagocytic assay.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Bacterial / blood
  • Antigens, Bacterial / immunology*
  • Bacterial Proteins / immunology
  • Bacterial Vaccines / administration & dosage
  • Bacterial Vaccines / immunology*
  • Blood Bactericidal Activity
  • Disease Models, Animal
  • Enterococcus faecalis / immunology*
  • Enterococcus faecium / immunology*
  • Gram-Positive Bacterial Infections / microbiology
  • Gram-Positive Bacterial Infections / pathology
  • Gram-Positive Bacterial Infections / prevention & control*
  • Immunity, Heterologous
  • Immunoglobulin G / blood
  • Male
  • Mice, Inbred BALB C
  • Microbial Viability
  • Opsonin Proteins / blood
  • Phagocytosis
  • Polysaccharides, Bacterial / immunology
  • Rabbits
  • Treatment Outcome
  • Vaccines, Conjugate / administration & dosage
  • Vaccines, Conjugate / immunology
  • Vaccines, Subunit / administration & dosage
  • Vaccines, Subunit / immunology


  • Antibodies, Bacterial
  • Antigens, Bacterial
  • Bacterial Proteins
  • Bacterial Vaccines
  • Immunoglobulin G
  • Opsonin Proteins
  • Polysaccharides, Bacterial
  • Vaccines, Conjugate
  • Vaccines, Subunit