Abstract
Immunoglobulins A (IgA) are crucially involved in protection of human mucosal surfaces from microbial pathogens. In this work, we devised and expressed in plants recombinant chimeric antifungal antibodies (Abs) of isotype A (IgA1, IgA2, and scFvFcA1), derived from a murine mAb directed to the fungal cell wall polysaccharide β-glucan which had proven able to confer protection against multiple pathogenic fungi. All recombinant IgA (rIgA) were expressed and correctly assembled in dimeric form in plants and evaluated for yield, antigen-binding efficiency and antifungal properties in vitro, in comparison with a chimeric IgG1 version. Production yields and binding efficiency to purified β-glucans showed significant variations not only between Abs of different isotypes but also between the different IgA formats. Moreover, only the dimeric IgA1 was able to strongly bind cells of the fungal pathogen Candida albicans and to restrain its adhesion to human epithelial cells. Our data indicate that IgG to IgA switch and differences in molecular structure among different rIgA formats can impact expression in plant and biological activity of anti-β-glucans Abs and provide new insights for the design of recombinant IgA as anti-infective immunotherapeutics, whose potential is still poorly investigated.
| Original language | English |
|---|---|
| Pages (from-to) | 2729-2738 |
| Number of pages | 10 |
| Journal | Biotechnology and Bioengineering |
| Volume | 114 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - Dec 1 2017 |
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Keywords
- anti-infectious IgA
- antigen binding efficiency
- fungal infections
- immunotherapy
- plant pharming
- recombinant IgA
ASJC Scopus subject areas
- Biotechnology
- Bioengineering
- Applied Microbiology and Biotechnology
Cite this
Comparative analysis of plant-produced, recombinant dimeric IgA against cell wall β-glucan of pathogenic fungi. / Capodicasa, Cristina; Catellani, Marcello; Moscetti, Ilaria; Bromuro, Carla; Chiani, Paola; Torosantucci, Antonella; Benvenuto, Eugenio.
In: Biotechnology and Bioengineering, Vol. 114, No. 12, 01.12.2017, p. 2729-2738.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Comparative analysis of plant-produced, recombinant dimeric IgA against cell wall β-glucan of pathogenic fungi
AU - Capodicasa, Cristina
AU - Catellani, Marcello
AU - Moscetti, Ilaria
AU - Bromuro, Carla
AU - Chiani, Paola
AU - Torosantucci, Antonella
AU - Benvenuto, Eugenio
PY - 2017/12/1
Y1 - 2017/12/1
N2 - Immunoglobulins A (IgA) are crucially involved in protection of human mucosal surfaces from microbial pathogens. In this work, we devised and expressed in plants recombinant chimeric antifungal antibodies (Abs) of isotype A (IgA1, IgA2, and scFvFcA1), derived from a murine mAb directed to the fungal cell wall polysaccharide β-glucan which had proven able to confer protection against multiple pathogenic fungi. All recombinant IgA (rIgA) were expressed and correctly assembled in dimeric form in plants and evaluated for yield, antigen-binding efficiency and antifungal properties in vitro, in comparison with a chimeric IgG1 version. Production yields and binding efficiency to purified β-glucans showed significant variations not only between Abs of different isotypes but also between the different IgA formats. Moreover, only the dimeric IgA1 was able to strongly bind cells of the fungal pathogen Candida albicans and to restrain its adhesion to human epithelial cells. Our data indicate that IgG to IgA switch and differences in molecular structure among different rIgA formats can impact expression in plant and biological activity of anti-β-glucans Abs and provide new insights for the design of recombinant IgA as anti-infective immunotherapeutics, whose potential is still poorly investigated.
AB - Immunoglobulins A (IgA) are crucially involved in protection of human mucosal surfaces from microbial pathogens. In this work, we devised and expressed in plants recombinant chimeric antifungal antibodies (Abs) of isotype A (IgA1, IgA2, and scFvFcA1), derived from a murine mAb directed to the fungal cell wall polysaccharide β-glucan which had proven able to confer protection against multiple pathogenic fungi. All recombinant IgA (rIgA) were expressed and correctly assembled in dimeric form in plants and evaluated for yield, antigen-binding efficiency and antifungal properties in vitro, in comparison with a chimeric IgG1 version. Production yields and binding efficiency to purified β-glucans showed significant variations not only between Abs of different isotypes but also between the different IgA formats. Moreover, only the dimeric IgA1 was able to strongly bind cells of the fungal pathogen Candida albicans and to restrain its adhesion to human epithelial cells. Our data indicate that IgG to IgA switch and differences in molecular structure among different rIgA formats can impact expression in plant and biological activity of anti-β-glucans Abs and provide new insights for the design of recombinant IgA as anti-infective immunotherapeutics, whose potential is still poorly investigated.
KW - anti-infectious IgA
KW - antigen binding efficiency
KW - fungal infections
KW - immunotherapy
KW - plant pharming
KW - recombinant IgA
UR - http://www.scopus.com/inward/record.url?scp=85029233306&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85029233306&partnerID=8YFLogxK
U2 - 10.1002/bit.26403
DO - 10.1002/bit.26403
M3 - Article
C2 - 28832951
AN - SCOPUS:85029233306
VL - 114
SP - 2729
EP - 2738
JO - Biotechnology and Bioengineering
JF - Biotechnology and Bioengineering
SN - 0006-3592
IS - 12
ER -