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.
Elahi
Shokrollah
S
Discipline of Immunology and Microbiology, Faculty of Health, David Maddison Clinical Science Building, Royal Newcastle Hospital, Newcastle NSW 2300, Australia.
Pang
Gerald
G
Clancy
Robert
R
D000284:Administration, Oral; D000818:Animals; D015415:Biomarkers; D002180:Candidiasis, Oral / Q000276:immunology* / Q000382:microbiology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005657:Fungal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D007779:Lactobacillus acidophilus; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D009055:Mouth / Q000382:microbiology; D009569:Nitric Oxide / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012463:Saliva / Q000378:metabolism; D013997:Time Factors
D015415:Biomarkers; D016207:Cytokines; D005657:Fungal Vaccines; D015847:Interleukin-4; D009569:Nitric Oxide; D007371:Interferon-gamma