Efficient production of recombinant secretory IgA against Clostridium difficile toxins in CHO-K1 cells
Venugopal Bhaskara, Maria Trinidad Leal, Jacqueline Seigner, Theresa Friedrich, Emanuel Kreidl, Elisabeth Gadermaier, Manfred Tesarz, Azra Rogalli, Laura Stangl, Jacqueline Wallwitz, Katharina Hammel, Mario Rothbauer, Herwig P. Moll, Peter Ertl, Rainer Hahn, Gottfried Himmler, Anton Bauer, Emilio Casanova
Abstract
Despite the essential role secretory IgAs play in the defense against pathogenic invasion and the proposed value of recombinant secretory IgAs as novel therapeutics, currently there are no IgA-based therapies in clinics. Secretory IgAs are complex molecules and the major bottleneck limiting their therapeutic potential is a reliable recombinant production system. In this report, we addressed this issue and established a fast and robust production method for secretory IgAs in CHO-K1 cells using BAC-based expression vectors. As a proof of principle, we produced IgAs against Clostridium difficile toxins TcdA and TcdB. Recombinant secretory IgAs produced using our expression system showed comparable titers to IgGs, widely used as therapeutic biologicals. Importantly, secretory IgAs produced using our method were functional and could efficiently neutralize Clostridium difficile toxins TcdA and TcdB. These results show that recombinant secretory IgAs can be efficiently produced, thus opening the possibility to use them as therapeutic agents in clinics.