Anti-β-glucan antibodies in healthy human subjects

Previous data by our group demonstrated the antifungal efficacy of a vaccine consisting of laminarin (β-(1,3)-glucan), conjugated with diphtheria toxoid, which generated protective anti-laminarin antibodies in mice. In this paper, we sought for the presence, isotype and subclass composition of natural anti-laminarin antibodies in an unselected population of human healthy subjects, in a comparison with antibodies directed against β-(1,6)-glucan (pustulan) and branched β-(1,3/1,6)-glucan (Pool 1) and mannan from Candida albicans. Almost all subjects showed detectable levels of anti-β-glucan antibodies, with IgG largely prevailing on IgM, little, if any, IgA and no IgE. However, the titer of anti-β-glucan antibodies was overall about 1 log lower than that of anti-mannan antibodies of the corresponding isotype. In particular, the level of anti-laminarin IgG was the lowest one, its geometrical mean titer (95% confidence interval, CI) being 1838 (1245–2714) as compared to 8157 (6067–10,931) and 3940 (2911–5332) for pustulan and Pool 1 fungal glucan, respectively. Analysis of IgG subclass composition showed that IgG2 was the prevalent subclass against any antigen, and again the concentration of anti-laminarin IgG2 was the lowest one, its geometrical mean concentration being 0.13 (0.07–0.24) μg/ml as compared to anti-pustulan and anti-Pool 1 glucan and mannan IgG2 levels, which were 0.33 (0.2–0.5), 1.35 (0.9–2.0), and 36.1 (25.2–51.3) μg/ml, respectively. These data show that anti-laminarin antibodies are present at low levels in humans as compared to other anti-β-glucan and, mostly, anti-mannan antibodies, and suggest that a protective antifungal vaccination in humans should attempt to tip the balance of antifungal antibodies in favour of the anti-laminarin ones.