We previously reported that the
IgM MAb B6.1, specific for β-1,2-mannotriose on the surface of the cell wall of Candida albicans, prevents mice from disseminated
candidiasis. The preventive activity of the antibody is mediated by enhanced phagocytosis that caused killing of the fungus and involvement of the
complement system. In the present study, MAb B6.1 was tested if the antibody enhances therapeutic efficacy of
amphotericin B (
Amp B) in a murine model of disseminated
candidiasis due to C. albicans. Determination by the kidneys-cfu (colony forming unit) and survival times was used to assess treatment. Mice treated intraperitoneally with MAb B6.1 at 1h post-
infection with C. albicans (5 x 10⁵ yeast cells/mouse) developed fewer 28%cfu and prolonged survival rates than negative controls, whereas administration of B6.1 to mice at 2h post-
infection was ineffective.
Therapeutic effect of
Amp B on mice with the disseminated disease was dose-dependent, but dosage of
Amp B (0.5mg/kg
body weight of mice) was not effective. A combination of MAb B6.1 given at 1h post-
infection plus
Amp B (0.5mg dose) enhanced survival times beyond the effect due to only antibody (P<0.05). The MST (mean survival times) value resulted from the combination
therapy-received mice was as almost the same as MST value from 2mg dose of
Amp B-given animals (P<0.05). In case mice given a combination of
Amp B (0.5mg dose) plus MAb B6.1 at 2h post-
infection - a condition of developing no therapeutic efficacy, the combination also reduced disease severity. All these data indicate that MAb B6.1 acts in concert with
Amp B, the antibody enhances therapeutic efficacy of
Amp B, and this combination
therapy augments protection which implies a possibility of reducing
Amp B dose. The augmentation of the response appeared to be specific because an irrelevant
IgM carbohydrate-specific MAb was not protective. In conclusion, these studies show that
Amp B combined with MAb B6.1 may be an option of solving the problem of limited antifungal
drug choices due to
drug-resistant C. albicans.