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Plant production of anti-β-glucan antibodies for immunotherapy of fungal infections in humans

TitoloPlant production of anti-β-glucan antibodies for immunotherapy of fungal infections in humans
Tipo di pubblicazioneArticolo su Rivista peer-reviewed
Anno di Pubblicazione2011
AutoriCapodicasa, Cristina, Chiani P., Bromuro C., De Bernardis F., Catellani Marcello, Palma A.S., Liu Y., Feizi T., Cassone A., Benvenuto Eugenio, and Torosantucci A.
RivistaPlant Biotechnology Journal
Parole chiaveanimal, animal model, Animalia, Animals, Antibodies, Antigens, article, Aspergillus fumigatus, beta glucan, beta-Glucans, biosynthesis, Candida albicans, candidiasis, cell adhesion, Cell Line, Cell Wall, Cryptococcus neoformans, development and aging, Female, Filobasidiella neoformans, Fungal, Fungi, fungus antibody, fungus antigen, genetics, growth, human, Humans, hybrid protein, immunoglobulin Fc fragment, Immunoglobulin Fc Fragments, immunoglobulin G, immunology, immunotherapy, metabolism, Mice, microbiology, Models, Monoclonal, Monoclonal antibody, mouse, Murinae, Mycoses, mycosis, Nicotiana benthamiana, physiology, plant leaf, Plant leaves, Plantibodies, plantibody, rat, Rats, Recombinant Fusion Proteins, single chain fragment variable antibody, Single-Chain Antibodies, Tobacco

There is an increasing interest in the development of therapeutic antibodies (Ab) to improve the control of fungal pathogens, but none of these reagents is available for clinical use. We previously described a murine monoclonal antibody (mAb 2G8) targeting β-glucan, a cell wall polysaccharide common to most pathogenic fungi, which conferred significant protection against Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans in animal models. Transfer of this wide-spectrum, antifungal mAb into the clinical setting would allow the control of most frequent fungal infections in many different categories of patients. To this aim, two chimeric mouse-human Ab derivatives from mAb 2G8, in the format of complete IgG or scFv-Fc, were generated, transiently expressed in Nicotiana benthamiana plants and purified from leaves with high yields (approximately 50mg Ab/kg of plant tissues). Both recombinant Abs fully retained the β-glucan-binding specificity and the antifungal activities of the cognate murine mAb against C. albicans. In fact, they recognized preferentially β1,3-linked glucan molecules present at the fungal cell surface and directly inhibited the growth of C. albicans and its adhesion to human epithelial cells in vitro. In addition, both the IgG and the scFv-Fc promoted C. albicans killing by isolated, human polymorphonuclear neutrophils in ex vivo assays and conferred significant antifungal protection in animal models of systemic or vulvovaginal C. albicans infection. These recombinant Abs represent valuable molecules for developing novel, plant-derived immunotherapeutics against candidiasis and, possibly, other fungal diseases. © 2011 The Authors. Plant Biotechnology Journal © 2011 Society for Experimental Biology, Association of Applied Biologists and Blackwell Publishing Ltd.


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Citation KeyCapodicasa2011776