title: Human domain antibodies against virulence traits of Candida albicans inhibit fungus adherence to vaginal epithelium and protect against experimental vaginal candidiasis.
abstract: Antibody variable domains (domain antibodies [DAbs]) are genetically engineered antibody fragments that include individual heavy-chain (VH) or kappa-chain (Vkappa) variable domains and lack the Fc region. Human DAbs against the 65-kDa mannoprotein (MP65) or the secretory aspartyl proteinase (SAP)-2 of Candida albicans (monospecific DAbs) or against both fungal antigens (heterodimeric, bispecific DAbs) were generated from phage expression libraries. Both monospecific and bispecific DAbs inhibited fungus adherence to the epithelial cells of rat vagina and accelerated the clearance of vaginal infection with the fungus. When heterodimeric DAbs were used, the clearance of infection was at least equivalent to treatment with fluconazole. The in vivo protective effects of DAbs were demonstrated by both pre- and postchallenge schedules of DAb administration and with both fluconazole-susceptible and fluconazole-resistant strains of C. albicans. This is the first demonstration that human DAbs lacking the Fc constituent can efficiently control an infection and can act largely by inhibiting adherence.
authors.affiliation: Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Viale Regina Elena, 00161 Rome, Italy.
authors.forename: Flavia
authors.initials: F
authors.lastname: De Bernardis
authors.forename: Haiqun
authors.initials: H
authors.lastname: Liu
authors.forename: Rachel
authors.initials: R
authors.lastname: O'Mahony
authors.forename: Roberto
authors.initials: R
authors.lastname: La Valle
authors.forename: Silvia
authors.initials: S
authors.lastname: Bartollino
authors.forename: Silvia
authors.initials: S
authors.lastname: Sandini
authors.forename: Steven
authors.initials: S
authors.lastname: Grant
authors.forename: Neil
authors.initials: N
authors.lastname: Brewis
authors.forename: Ian
authors.initials: I
authors.lastname: Tomlinson
authors.forename: Rachel C
authors.initials: RC
authors.lastname: Basset
authors.forename: John
authors.initials: J
authors.lastname: Holton
authors.forename: Ivan M
authors.initials: IM
authors.lastname: Roitt
authors.forename: Antonio
authors.initials: A
authors.lastname: Cassone
mesh_terms: D000818:Animals; D000908:Antibodies, Fungal / Q000276:immunology*; D016282:Aspartic Acid Endopeptidases / Q000276:immunology; D002176:Candida albicans / Q000201:enzymology / Q000472:pathogenicity / Q000502:physiology*; D002181:Candidiasis, Vulvovaginal / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004848:Epithelium / Q000382:microbiology* / Q000473:pathology; D005260:Female; D005656:Fungal Proteins / Q000276:immunology; D006801:Humans; D050440:Immunoglobulin Subunits / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000276:immunology; D051381:Rats; D014621:Vagina / Q000276:immunology* / Q000473:pathology; D014774:Virulence
chemical_list: D000908:Antibodies, Fungal; D005656:Fungal Proteins; D050440:Immunoglobulin Subunits; D008562:Membrane Glycoproteins; C025363:mannoproteins; D016282:Aspartic Acid Endopeptidases; C090753:SAP2 protein, Candida