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9. Synthetic glycopeptide vaccines combining [beta]-mannan and peptide epitopes induce protection against candidiasis

Author

Xin, Hong, Dziadek, Sebastian, Bundle, David R., and Cutler, Jim E.

Subjects
Candidiasis -- Prevention, Peptides -- Health aspects, Vaccines -- Research, Glycogen -- Health aspects, Candida albicans -- Physiological aspects, Science and technology
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).sub.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).sub.3]-Fba, [beta]-[(Man).sub.3]-Met6 and [beta]-[(Man).sub.3]-Hwp1 induced protection evidenced by survival and reduced kidney fungal burden, the [beta]-[(Man).sub.3]-Eno1 and [beta]-[(Man).sub.3]-Gap1 gave moderate protection, and the [beta]-[(Man).sub.3]-Pgk1 slightly enhanced disease. For the [beta]-[(Man).sub.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. Candida albicans | glycopeptide conjugate | prevention

Published
2008

11. Yeast wall protein 1 of Candida albicans

Author

Granger, Bruce L., Flenniken, Michelle L., Davis, Dana A., Mitchell, Aaron P., and Cutler, Jim E.

Subjects
DNA -- Research, Yeast fungi -- Genetic aspects, Candida albicans -- Genetic aspects, Proteins -- Research, Biological sciences
Abstract

Yeast wall protein 1 (Ywp1, also called Pga24) of Candida albicans is predicted to be a 533 aa polypeptide with an N-terminal secretion signal, a C-terminal glycosylphosphatidylinositol anchor signal and a central region rich in serine and threonine. In yeast cultures, Ywp1p appeared to be linked covalently to glucans of the wall matrix, but, as cultures approached stationary phase, Ywp1p accumulated in the medium and was extractable from cells with disulfide-reducing agents. An 11 kDa propeptide of Ywp1p was also present in these soluble fractions; it possessed the sole N-glycan of Ywp1p and served as a useful marker for Ywp1p. DNA vaccines encoding all or part of Ywp1p generated analytically useful antisera in mice, but did not increase survival times for disseminated candidiasis. Replacement of the coding sequence of YWP1 with the fluorescent reporter GFP revealed that expression of YWP1 is greatest during yeast exponential-phase growth, but downregulated in stationary phase and upon filamentation. Expression was upregulated when the extracellular phosphate concentration was low. Disruption by homologous recombination of both YWP1 alleles resulted in no obvious change in growth, morphology or virulence, but the Ywp1p-deficient blastoconidia exhibited increased adhesiveness and biofilm formation, suggesting that Ywp1p may promote dispersal of yeast forms of C. albicans.

Published
2005

13. Title fight

Author

Cutler, Jim, Goldberg, Ron, and Salvator, Dave

Subjects
Technology Information, Technology overview, Sound board/audio device, Sound/audio software, Multimedia Technology, User need, Hardware Selection, Software Selection
Published
1995

14. Sound of music

Author

Cutler, Jim, Goldberg, Ron, and Salvator, Dave

Subjects
MIDI, Technology Information, Technology overview, User need, Hardware Selection, Software Selection
Published
1995

15. The primer

Author

Cutler, Jim, Goldberg, Ron, and Salvator, Dave

Subjects
Sound processing equipment, Multimedia Technology, Technology Information, Technology overview, User need
Published
1995

16. Booming business

Author

Cutler, Jim, Goldberg, Ron, and Sakvator, Dave

Subjects
Technology overview, Technology Information, Sound processing equipment, Presentation graphics software, Sound/audio software, Sound board/audio device, User need
Published
1995

31. Getting creative just got easier: Orchid blooms with PnP

Author

Cutler, Jim

Subjects
Hardware multiproduct review, Sound board/audio device, Orchid Technology Inc. -- Product information, Creative Labs Inc. -- Product information, Creative Labs Sound Blaster AWE32 PnP (Sound board) -- Evaluation, Orchid Technology NuSound PnP 32 (Sound board) -- Evaluation
Published
1996

35. Crank up the volume

Author

Cutler, Jim, Goldberg, Ron, and Salvator, Dave

Subjects
Sound processing equipment, Multimedia Technology, Technology Information, Technology overview, Sound board/audio device
Published
1995

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