Immunogenic and protective Candida albicans constituents

Candida albicans is an opportunistic fungus which has become an increasingly common cause of disease in the immunocompromised or otherwise modified host. Mucocutaneous involvement is especially common in patients with defective cell-mediated immunity (CMI), such as those with AIDS, whereas deep-seated candidiasis is more prevalent in neutropenic patients. Although the fungus possesses an array of low-penetrance "virulence" factors, a defective immune response is usually a prerequisite for serious candidal infections to occur. On the other hand, C. albicans is an ordinary commensal of the human gastrointestinal (GI) tract, and its presence is sensed by the immune system of the healthy subject which responds in terms of intense Candida-specific and non-specific immunomodulatory effects. Thus, Candida is a microorganism which interacts safely and, perhaps, even beneficially (as non-specific immunomodulator) in a normal host, but pathologically in a predisposed subject. In order to understand host-fungus interactions in both categories of subjects, it is essential to study: i) the fungal components which elicit, modulate or suppress host immune responses; ii) how these components are expressed during Candida growth and morphogenesis in vitro and in vivo; iii) the immunoregulatory mechanisms underlying protective and non-protective antifungal responses. These studies are fundamental to the design and realization of candidal diagnostics and vaccines. Although the commensal nature of C. albicans is clearly an obstacle to the idea itself of a classical prophylactic vaccine (i.e. one which protects an uninfected individual), there are no conceptual lags to the use of a therapeutic vaccine, meaning the capacity of particular candidal components to stimulate specific immunity against the passage from a commensal or latent infectious state to overt disease, and/or fostering a protective immune response during the disease itself.