Efficacy of combination immunotherapy of IgM MAb B6.1 and amphotericin B against disseminated candidiasis

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 1 h post-infection with C. albicans (5 × 105 yeast cells/mouse) developed fewer 28% cfu and prolonged survival rates than negative controls, whereas administration of B6.1 to mice at 2 h post-infection was ineffective. Therapeutic effect of Amp B on mice with the disseminated disease was dose-dependent, but dosage of Amp B (0.5 mg/kg body weight of mice) was not effective. A combination of MAb B6.1given at 1 h post-infection plus Amp B (0.5 mg 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 2 mg dose of Amp B-given animals (P < 0.05). In case mice given a combination of Amp B (0.5 mg dose) plus MAb B6.1 at 2 h 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

Research Highlights
► MAb B6.1 is found to have therapeutic effect to Candida albicans infection.
► B6.1 acts in concert with amphotericin B (Amp B), enhancing Amp B efficacy.
► Combination of B6.1 and Amp B augments protection to the fungal infection.
► Combination may reduce side effects of Amp B by decreasing its common dose.