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

Publisher: Wiley on behalf of the Society for Experimental Biology, Association of Applied Biologists Country of Publication: England NLM ID: 101201889 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1467-7652 (Electronic) Linking ISSN: 14677644 NLM ISO Abbreviation: Plant Biotechnol J Subsets: MEDLINE

Publication: 2014- : Oxford Wiley on behalf of the Society for Experimental Biology, Association of Applied Biologists
Original Publication: [Oxford] : Blackwell Pub., c2003-

Immunotherapy*; Antibodies, Fungal/*immunology ; Candida albicans/*immunology ; Candidiasis/*therapy ; Nicotiana/*immunology ; beta-Glucans/*immunology; Animals ; Antibodies, Fungal/biosynthesis ; Antibodies, Fungal/genetics ; Antibodies, Fungal/therapeutic use ; Antibodies, Monoclonal/biosynthesis ; Antibodies, Monoclonal/genetics ; Antibodies, Monoclonal/immunology ; Antibodies, Monoclonal/therapeutic use ; Antigens, Fungal/immunology ; Aspergillus fumigatus/immunology ; Candida albicans/growth & development ; Candida albicans/physiology ; Candidiasis/microbiology ; Cell Adhesion/immunology ; Cell Line ; Cell Wall/immunology ; Cryptococcus neoformans/immunology ; Female ; Humans ; Immunoglobulin Fc Fragments/genetics ; Immunoglobulin Fc Fragments/metabolism ; Immunoglobulin G/genetics ; Immunoglobulin G/metabolism ; Mice ; Models, Animal ; Mycoses/microbiology ; Mycoses/therapy ; Plant Leaves/genetics ; Plant Leaves/metabolism ; Plantibodies/genetics ; Plantibodies/immunology ; Plantibodies/metabolism ; Plantibodies/therapeutic use ; Rats ; Recombinant Fusion Proteins/immunology ; Recombinant Fusion Proteins/metabolism ; Single-Chain Antibodies/genetics ; Single-Chain Antibodies/metabolism ; Nicotiana/genetics ; beta-Glucans/metabolism

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 50 mg 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.)

United Kingdom Medical Research Council

0 (Antibodies, Fungal)
0 (Antibodies, Monoclonal)
0 (Antigens, Fungal)
0 (Immunoglobulin Fc Fragments)
0 (Immunoglobulin G)
0 (Plantibodies)
0 (Recombinant Fusion Proteins)
0 (Single-Chain Antibodies)
0 (beta-Glucans)

Date Created: 20110127 Date Completed: 20111201 Latest Revision: 20231213

20250114

10.1111/j.1467-7652.2010.00586.x

21265996