Synthetic glycopeptide vaccines combining beta-mannan and peptide epitopes induce protection against candidiasis

Proc Natl Acad Sci U S A. 2008 Sep 9;105(36):13526-31. doi: 10.1073/pnas.0803195105. Epub 2008 Aug 25.

Abstract

The first fully synthetic glycopeptide vaccines against a fungal disease have been used to combat disseminated candidiasis in mice. Six T cell peptides found in Candida albicans cell wall proteins were selected by algorithm peptide epitope searches; each was synthesized and conjugated to the fungal cell wall beta-mannan trisaccharide [beta-(Man)(3)] by novel saccharide-peptide linker chemistry to create glycopeptide conjugates. The six proteins were selected because of expression during human candidiasis and cell wall association and included: fructose-bisphosphate aldolase (Fba); methyltetrahydropteroyltriglutamate (Met6); hyphal wall protein-1 (Hwp1); enolase (Enol); glyceraldehyde-3-phosphate dehydrogenase (Gap1); and phosphoglycerate kinase (Pgk1). By immunization protocols favoring production of protective antibody, the beta-(Man)(3)-Fba, beta-(Man)(3)-Met6 and beta-(Man)(3)-Hwp1 induced protection evidenced by survival and reduced kidney fungal burden, the beta-(Man)(3)-Eno1 and beta-(Man)(3)-Gap1 gave moderate protection, and the beta-(Man)(3)-Pgk1 slightly enhanced disease. For the beta-(Man)(3)-Fba conjugate, protection was uniquely acquired through immunity against the carbohydrate and the Fba peptide. This approach based on fully synthetic chemically defined immunogens should be generally useful in vaccine development.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / immunology
  • Antibody Formation / immunology
  • Candidiasis / immunology*
  • Candidiasis / prevention & control*
  • Cells, Cultured
  • Epitopes / immunology*
  • Female
  • Fructose-Bisphosphate Aldolase / metabolism
  • Glycopeptides / chemical synthesis*
  • Glycopeptides / chemistry
  • Glycopeptides / immunology*
  • Mannans / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Molecular Structure
  • Oligosaccharides / immunology
  • Vaccines, Synthetic / immunology

Substances

  • Antibodies
  • Epitopes
  • Glycopeptides
  • Mannans
  • Oligosaccharides
  • Vaccines, Synthetic
  • Fructose-Bisphosphate Aldolase