Human domain antibodies against virulence traits of Candida albicans inhibit fungus adherence to vaginal epithelium and protect against experimental vaginal candidiasis.

De Bernardis, Flavia and Liu, Haiqun and O'Mahony, Rachel and La Valle, Roberto and Bartollino, Silvia and Sandini, Silvia and Grant, Steven and Brewis, Neil and Tomlinson, Ian and Basset, Rachel C. and Holton, John and Roitt, Ivan and Cassone, Antonio (2007) Human domain antibodies against virulence traits of Candida albicans inhibit fungus adherence to vaginal epithelium and protect against experimental vaginal candidiasis. Journal of Infectious Diseases, 195 (1). pp. 149-157. ISSN 1537-6613

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Official URL: http://www.journals.uchicago.edu/doi/full/10.1086/...

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Abstract

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.

Item Type:Article
Research Areas:Middlesex University Schools and Centres > School of Science and Technology > Natural Sciences
Middlesex University Schools and Centres > School of Science and Technology > Natural Sciences > Biomarkers for Cancer group
Citations on ISI Web of Science:37
ID Code:4035
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Deposited On:11 Feb 2010 11:33
Last Modified:24 Nov 2014 16:41

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