Functional and protective capacity of a human monoclonal antibody against Shigella sonnei O-Antigen produced in fungal cells

ABSTRACT The number of bacterial species acquiring antimicrobial resistance to the most widely used antibiotics is steadily increasing. Monoclonal antibodies (mAbs) are among the most promising therapeutic options to tackle antimicrobial resistance. A major hurdle that prevents broader applicability of mAb therapy is represented by high production costs. Here, we describe the manufacturing of a human mAb targeting the O-Antigen of Shigella sonnei by a fungal production platform ( Thermothelomyces heterothallica C1, formerly Myceliophthora thermophila ). The antibody, produced with either native fungal or humanized glycosylation, had functional activity in vitro and protective efficacy in vivo comparable to the antibody generated in standard mammalian cells. The use of the C1 platform reduces production time and accelerates release, thus significantly lowering production costs. This approach can favor equitable access to novel therapeutics that can counteract global health challenges. IMPORTANCE This study demonstrates that a fungal production platform can produce a human monoclonal antibody (mAb) targeting the O‑antigen of Shigella sonnei with equivalent functional activity and protective effects to antibodies made in mammalian cells. The use of the C1 platform reduces production time and accelerates release, thus significantly lowering production costs. This approach can favor equitable access to novel therapeutics and support global efforts to control antimicrobial resistance.