Plant-produced monoclonal antibodies recognize the native circumsporozoite protein on Plasmodium falciparum sporozoites

Malaria is primarily caused by Plasmodium parasites and remains a major global health threat due to drug resistance and limited vaccine efficacy. Monoclonal antibodies (mAbs) targeting the conserved NANP repeat region of the circumsporozoite protein (PfCSP), such as MS-1797, represent a promising prophylactic strategy. Here, we demonstrate the plant-based production of MS-1797 in glycoengineered Nicotiana benthamiana ΔXF. Two variants were generated: MS-01 (original MS-1797) and MS-02 (MS-1797-SEKDEL), which yielded up to 457.3 µg/g fresh weight and 415.7 µg/g FW at 6 days post-infiltration. The plant-derived mAbs were obtained in high purity (>90%) and displayed either human core glycans or high mannose structures. Notably, both MS-01 and MS-02 retained antigen specificity in vitro and bound native PfCSP on sporozoites by immunofluorescence assay. These results establish the feasibility of producing functional anti-malarial mAbs in plants and highlight their potential use as affordable reagents for malaria research, diagnostics, and future prophylactic interventions.