Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 105, Issue 36, Pages 13526-13531Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0803195105
Keywords
Candida albicans; glycopeptide conjugate; prevention
Categories
Funding
- National Institutes of Health-National Institute of Allergy
- Infectious Diseases [RO1 A124912, PO1 A1061537]
- Research Institute for Children
- Deutscher Akademischer Austauschdienst
- Alberta Heritage Foundation for Medical Research
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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); glyceraidehyde-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.
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