Production of the 42‐kDa fragment of Plasmodium falciparum merozoite surface protein 1, a leading malaria vaccine antigen, in Arabidopsis thaliana seeds

Summary Malaria is widely associated with poverty, and a low‐cost vaccine against malaria is highly desirable for implementing comprehensive vaccination programmes in developing countries. Production of malaria antigens in plants is a promising approach, but its development has been hindered by poor expression of the antigens in plant cells. In the present study, we targeted plant seeds as a low‐cost vaccine production platform and successfully expressed the Plasmodium falciparum 42‐kDa fragment of merozoite surface protein 1 (MSP1 42 ), a leading malaria vaccine candidate, at a high level in transgenic Arabidopsis seeds. We overcame hurdles of transcript and protein instabilities of MSP1 42 in plants by synthesizing a plant‐optimized MSP1 42 cDNA and either targeting the recombinant protein to protein storage vacuoles or fusing it with a stable plant storage protein. An exceptional improvement in MSP1 42 expression, from an undetectable level to 5% of total extractable protein, was achieved with these combined strategies. Importantly, the plant‐derived MSP1 42 maintains its natural antigenicity and can be recognized by immune sera from malaria‐infected patients. Our results provide a strong basis for the development of a plant‐based, low‐cost malaria vaccine.