Human Domain Antibodies against Virulence Traits of Candida albicans Inhibit Fungus Adherence to Vaginal Epithelium and Protect against Experimental Vaginal Candidiasis

• Published in: The Journal of infectious diseases Vol. 195; no. 1; pp. 149 - 157
• Main Authors: De Bernardis, Flavia, Liu, Haiqun, O’Mahony, Rachel, La Valle, Roberto, Bartollino, Silvia, Sandini, Silvia, Grant, Steven, Brewis, Neil, Tomlinson, Ian, Basset, Rachel C., Holton, John, Roitt, Ivan M., Cassone, Antonio
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 01-01-2007; University of Chicago Press; Oxford University Press
• Subjects: Animals; Antibodies; Antibodies, Fungal - immunology; Aspartic Acid Endopeptidases - immunology; Bacteriophages; Biological and medical sciences; Candida albicans; Candida albicans - enzymology; Candida albicans - pathogenicity; Candida albicans - physiology; Candidiasis; Candidiasis, Vulvovaginal - metabolism; Candidiasis, Vulvovaginal - pathology; Candidiasis, Vulvovaginal - prevention & control; Epithelium - microbiology; Epithelium - pathology; Female; Fundamental and applied biological sciences. Psychology; Fungal Proteins - immunology; Fungi; Humans; Immunoglobulin Subunits - metabolism; Infections; Infectious diseases; Life Sciences; Medical sciences; Membrane Glycoproteins - immunology; Microbiology; Miscellaneous; Mycology; Other; Rats; Statistical results; Statistical significance; Vaccination; Vagina - immunology; Vagina - pathology; Virulence; Candida albicans; Human; Candidiasis; Yeast; Mycosis; Microbiology; Antibody; Virulence; Vagina; Epithelium; Adhesion; Fungi; Infection; Fungi Imperfecti; Thallophyta; experimental vaginal candidiasis; candida albicans; human domain antibody; adherence
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/509891

Antibody variable domains (domain antibodies [DAbs]) are genetically engineered antibody fragments that include individual heavy-chain (VH) or κ-chain (Vκ) 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