Efficacy of Recombinant Human Mannose Binding Lectin Alone and in Combination with Itraconazole Against Murine Candida albicans vaginitis

Abstract

Mannan binding lectin (MBL) deficiency has been associated with increased susceptibility to vaginitis in humans due to Candida albicans. In these studies we assessed the utility of recombinant human MBL (rhMBL) as a therapeutic against experimental C. albicans vaginitis. After intravenous treatment of uninfected mice with 75 μg of rhMBL, rhMBL was detected in the serum and peritoneal lavage fluid; rhMBL was detected in the serum of infected mice 2 and 24 hours post-dose, and at very low concentrations in vaginal lavage fluid. Intravenous treatment with rhMBL alone or in combination with oral itraconazole enhanced the clearance of C. albicans from the vagina of wild-type or MBL gene knockout (KO) mice; rhMBL was modestly effective alone. However, rhMBL in combination with itraconazole was not better than itraconazole alone. Topical administration of rhMBL in a cream appeared more effective than rhMBL in a gel and both were inferior to commercial clotrimazole cream. Topical rhMBL cream in combination with itraconazole resulted in a 3-fold improvement in clearance of the yeast compared with sole itraconazole therapy. Overall, these data indicate that rhMBL may have utility in the treatment of candidal vaginitis when used as an adjunctive therapy.

• Mannose binding lectin
• MBL
• vaginitis
• Candida albicans
• Candidal vaginitis

ACKNOWLEDGMENTS

These studies were funded in part by NatImmune A/S.

Declaration of interest: Author M. Axelsen was employed by NatImmune A/S at the time these studies were performed. The authors report no other conflicts of interest. The authors alone are responsible for the content and writing of the paper.