Development of surrogate markers for oral immunisation against Candida albicans

We have developed an oral vaccine using the blastococcoid form of Candida albicans with a murine model of oral candidiasis with infection-resistant (BALB/c) and infection-prone (DBA/2) mice. Previous studies had demonstrated that enhanced clearance was linked to increased production of both Th1 and Th2 cytokines (IFN-gamma and IL-4, respectively) in regional lymph nodes, and increased secretion of IFN-gamma and NO in saliva. Subsequent study using oral Lactobacillus acidophilus (LAVRI-A1) induced a local cytokine pattern and enhanced clearance of intra-oral C. albicans similar to that noted in animals given killed candida vaccine. Thus, the experiment was repeated with a 2 month gap between completion of a vaccine course and challenge with live C. albicans. Compared to control mice, those given the oral vaccine had a 4 log reduction in colonisation on day 2, associated with twice the levels of secretion of IFN-gamma and IL-4 from the regional node cells, five times the level of nitric oxide in saliva, and suppression of NO production with MMLA induced a 2 log increase in oral colonisation. Thus while both IFN-gamma and IL-4 appear to contribute to clearance of oral C. albicans, IL-4 appears to act through a paracrine enhancement of NO production. Studies in man are in progress to define similar surrogate markers of immune protection, prior to oral vaccine trial.