Protective antigens and mechanisms of anti-Candida immunity

Life threatening fungal diseases are now frequent in a substantial fraction of the immunocompromised host population. The toxicity and the relative scarcity of efficacious antifungal drugs highlight the need for developing alternative or integrative immunoprophylactic and therapeutic tools; among them the need to develop prophylactic or therapeutic vaccines against candidiasis, a widespread mucosal or deep-seated infection caused primarily by the fungus Candida albicans, are of clear priority. Vaccination is a highly beneficial medical practice, and probably the most cost-effective measure against disease onset and progression. It is based on the use of microbial antigens capable of conferring protection in a susceptible target host. To date, only a handful of Candida albicans antigens have been produced and very few of them have been thoroughly investigated for immunogenicity and protection in experimental models of candidiasis. Thus, approaches to the molecular, biochemical and functional characterization of novel C. albicans encoded molecules are most welcome to improve the perspective of developing in the near future an effective vaccine against C. albicans. Identification of anti-Candida vaccine candidates must take into account the diversity of Candida diseases, the various underlying mechanisms of protection as well as the major immune dysfunctions observed as predisposing factors for disease. Antigens to be considered possible vaccine candidates include members of the aspartyl proteinase (Sap2) family and the 65kDa mannoprotein (MP65) antigen. An additional molecule of C. albicans which has not yet been identified but deserves great consideration as a vaccine candidate is the yeast-killer toxin receptor (KTR). Initial experimental evidence strongly suggests that the above antigens are able to elicit protective immunity against mucosal and/or systemic candidiasis. A series of molecular, biochemical and immunological studies aimed at validating and strengthening this initial evidence are in progress, with the ultimate goal of producing recombinant or natural antigens that can be assessed for their ability to elicit a protective immunity in animal models and the mechanisms whereby protection is achieved, with emphasis on determination of immune correlates of protection.