Host Immune Responses to Saps

Very few studies have investigated the interaction between Saps and the host immune response. While high titres of anti-Sap IgG antibodies have been demonstrated in sera of candidiasis patients (Macdonald and Odds, 1980; Ruchel and Boning, 1983; Ruchel et al., 1988), few detailed studies on mucosal antibody responses, using saliva or vaginal secretions, against the Saps have been performed.

However, recently two reports have addressed this. In a small study of six patients with oral candidiasis and HIV infection, salivary IgA antibodies to Sapl and Sap6 were found to be raised in patients compared with controls. Serum IgG and IgA antibodies were also raised (Drobacheff et al., 2001). Similarly in a series of 15 patients with oral candidiasis and HIV infection, Millon et al. (2001) found salivary IgA antibodies to Sap2 and Sap6 to be raised and related to infection. These studies are suggestive of both inferences that responses in HIV are not impaired in this regard and that if shown to be specific, Sap1 and Sap6 may be expressed in such infections. Taken overall, the evidence would suggest that oral candidiasis can induce a response to both whole cells of Candida and to Candida Saps and would not exclude the possibility that such antibodies might subsequently be protective.

Preliminary data from our laboratory have demonstrated strong anti-Sap2 salivary IgA and serum IgG responses in mice after intranasal (i.n.) immunisation, indicating the immunogenic potential of the C. albicans proteinases. Furthermore, we have detected anti-Sap2 secretory IgA responses in human saliva of both Candida carriers and patients with C. albicans infections (Naglik et al., unpublished).

Although Sap2 is known to be immuno-genic and can induce antibody responses, the protective potential of Sap antibodies in vivo remains unclear. De Bernardis et al. (1997) showed a protective effect of anti-Sap2 IgA antibodies in experimental vaginitis in rats. This not only demonstrated that Sap2 contributed to vaginal infections and was a target of the host immune response, but also suggested that anti-Sap IgA antibodies could afford protection against C. albicans infections at mucosal sites in vivo.

No studies have yet reported the mechanisms of antibody protection or whether other members of the proteinase family can induce protective responses. Key questions remain such as whether Sap-specific antibodies can inhibit proteinase activity and whether passive immunisation could produce a protective or infection-attenuating response? Recently, we assessed the ability of saliva and serum, purified IgG, and Sap2-specific antibodies to inhibit C. albicans Sap2 proteinase activity, but found no strong evidence for Sap2 inhibition (Naglik et al., 2005). In addition, Borg et al. (1988) demonstrated that three monoclonal IgM antibodies raised against Sap2 did not inhibit enzyme activity. Furthermore, a C. albicans Sap-specific murine IgG monoclonal antibody was mapped to a specific region of Sap2 (Asp77-Gly103) but was also found not to inhibit Sap2 activity (Na et al., 1999). Another study used sera from patients with oral and systemic candidiasis to delineate six Sap2 epitopes, but human recombinant antibodies against two of these epitopes were not protective in a lethal mouse model of candidiasis (Ghadjari et al., 1997).

Identification of SIgA epitopes would arguably be more relevant than IgG or IgM epitopes to C. albicans infection at mucosal sites and it is quite conceivable that a cocktail of epitopes from different proteinases may be required before neutralising or protective antibody responses are attained against C. albicans infections.

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