SummaryMalaria 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.

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