Glucan-based vaccines

a glucan-based, vaccine technology, applied in the field of vaccines, can solve the problems low protective efficacy, and ineffective whole-cell vaccines, and achieve the effect of low protective efficacy

Inactive Publication Date: 2005-09-22
CASSONE ANTONIO +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0005]Candida cells contain all non-secreted candidate protective antigens but, even though they elicit high-level humoral and cell-mediated immune responses against various antigens, whole cell vaccines are ineffective. It has surprisingly been found that this low protective efficacy is not due to the absence of immune responses to particular antigens, but rather to the presence of blocking antib

Problems solved by technology

Candida cells contain all non-secreted candidate protective antigens but, even though they elicit high-level humoral and cell-mediated immune responses against various antigens, whole cell vaccines are ineffective.
It has surprisingly been found that this low protective efficacy is not due

Method used

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Examples

Experimental program
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Effect test

Embodiment Construction

Preparation of Mannoprotein-Depleted Yeast Cells

[0133]C. albicans strain BP, serotype A, from the type collection of the Istituto Superiore di Sanità (Rome, Italy), was routinely maintained on Sabouraud agar slants. For all experiments, fungus was cultured in the yeast form in liquid Winge medium at 28° C., washed twice in saline, counted in a haemocytometerer, and resuspended at the desired concentration in sterile saline.

[0134] For the preparation of normal cells (‘Y cells’) yeast cells suspensions (108 cells / ml) were inactivated at 80° C. for 30 min, washed and stored at 4° C. for no more than a week.

[0135] To prepare mannoprotein-depleted cells (‘YDP cells’), heat-inactivated Y cells as above (108 / ml) were treated with 50 mM DTT in 5 mM EDTANa2 (1 hour, 37° C.). 500 μg / ml Proteinase K (Sigma) was added to the digestion mixture and the cells were treated for one further hour at 37° C. The fungal cells were extensively washed with saline to remove enzyme, resuspended in saline...

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Abstract

Anti-glucan antibodies have been found to be protective against systemic fungal infection with C. albicans, but the protective efficacy can be inhibited by blocking antibodies. The invention provides an immunogenic composition comprising a glucan and a pharmaceutically acceptable carrier, characterised in that, when administered to a mammalian recipient, the composition elicits protective anti-glucan antibodies but does not elicit antibodies which inhibit the protective efficacy of the anti-glucan anti-bodies. The glucan may be presented on the surface of a protease-treated microbial cell or may be presented as a protein-glucan conjugate. The glucan may be substituted by a glucan mimotope, a peptidomimetic of a glucan mimotope, or nucleic acid encoding a mimotope. Anti-glucan-antibodies show broad spectrum microbicidal activity. B-glucans are preferred, particularly those containing one or more B-1,6 linkages

Description

TECHNICAL FIELD [0001] The invention relates to vaccines, more particularly those against fungal infections and disease. BACKGROUND ART [0002] Fungal infections are prevalent in several clinical settings, particularly in immunocompromised patients. The emergence of resistance to antimycotics, in particular to the azoles, has increased interest in therapeutic and prophylactic vaccination against these fungi [1]. Among fungal pathogens, Candida albicans is one of the most prevalent. This organism is one of the principal agents of widespread opportunistic infections in humans and causes candidiasis, a condition which is found in both normal and immunocompromised patients. There have been several attempts to provide anti-Candida vaccines. [0003] There is widespread consensus in the field of medical mycology that cellular immunity is critical for successful host defence against fungi [2], although the potential efficacy of humoral immunity in protecting against two major fungal pathogens...

Claims

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Application Information

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IPC IPC(8): A61K31/7088A61K31/716A61K35/76A61K36/06C12N15/09A61K38/00A61K39/00A61K39/05A61K39/09A61K39/13A61K39/145A61K39/155A61K39/205A61K39/29A61K39/385A61K39/39A61K39/395A61K45/00A61P31/00A61P31/04A61P31/06A61P31/10A61P33/02A61P33/08A61P43/00C07K14/00C07K16/14C12N1/14C12R1/725
CPCA61K39/0002A61K2039/505A61K2039/521C07K17/10A61K2039/6037C07K16/14A61K39/385A61K2039/55566A61P1/04A61P11/04A61P13/12A61P17/00A61P27/02A61P29/00A61P31/00A61P31/04A61P31/06A61P31/10A61P33/02A61P33/08A61P37/04A61P43/00Y02A50/30
Inventor CASSONE, ANTONIOPOLONELLI, LUCIANO
Owner CASSONE ANTONIO
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