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

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

Author information

1
Division of Pediatric Infectious Diseases, Dr. von Hauner Children's Hospital, Ludwig Maximillian's University, Munich, Germany.
2
Istituto di Microbiologia, Università Cattolica del Sacro Cuore, Rome, Italy.
3
Dipartimento di Scienze di Laboratorio e Infettivologiche, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy.
4
Department of Chemistry, Faculty of Sciences and Center for Advanced Scientific Research (CICA), Universidade da Coruña, A Coruña, Spain.

Abstract

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

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