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

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 Candi...

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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
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Summary:	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
Bibliography:	istex:31B62153C6E89F61BE9D334B9EC07D0D4AA385EC ark:/67375/HXZ-34939RF8-4 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0022-1899 1537-6613
DOI:	10.1086/509891