Glucan-based vaccines

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...

AI Technical Summary

Benefits of technology

[0020]β-glucans may be presented to the immune system on the surface of a fungal cell. As β-glucans are not normally exposed in sufficiently immunogenic form on the surface of fungal cells, however, the cells should be treated with protease (e.g. a non-specific protease, such as Proteinase K). Exposing fungi to protease in this way can deplete mannoprotein and remove molecules which elicit blocking antibodies.

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 to the absence of immune responses to particular antigens, but rather to the presence of blocking antibodies in animal serum which can interact with the intact fungus cell surface.

Fungal glucans are naturally poor immunogens and have not previously been considered for eliciting protection.

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