title: 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.
authors.affiliation: California Institute for Medical Research, San Jose, California, USA. clemons@cimr.org
authors.forename: Karl V
authors.initials: KV
authors.lastname: Clemons
authors.forename: Marife
authors.initials: M
authors.lastname: Martinez
authors.forename: Mads
authors.initials: M
authors.lastname: Axelsen
authors.forename: Steffen
authors.initials: S
authors.lastname: Thiel
authors.forename: David A
authors.initials: DA
authors.lastname: Stevens
mesh_terms: D000282:Administration, Intravaginal; D000284:Administration, Oral; D000818:Animals; D001826:Body Fluids / Q000378:metabolism; D002176:Candida albicans / Q000302:isolation & purification*; D002181:Candidiasis, Vulvovaginal / Q000188:drug therapy* / Q000382:microbiology; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D017964:Itraconazole / Q000008:administration & dosage / Q000627:therapeutic use*; D037601:Mannose-Binding Lectin / Q000008:administration & dosage / Q000097:blood / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use*; D016896:Treatment Outcome; D014621:Vagina / Q000378:metabolism / Q000382:microbiology; D014622:Vaginal Creams, Foams, and Jellies / Q000008:administration & dosage; D044364:Vaginal Douching
chemical_list: C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin; C445639:Mbl2 protein, mouse; D011994:Recombinant Proteins; D014622:Vaginal Creams, Foams, and Jellies; C069858:mannose binding protein A; D017964:Itraconazole