Production of the 42-kDa fragment of Plasmodium falciparum merozoite surface protein 1, a leading malaria vaccine antigen, in Arabidopsis thaliana seeds.
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 (MSP1₄₂), a leading malaria vaccine candidate, at a high level in transgenic Arabidopsis seeds. We overcame hurdles of transcript and protein instabilities of MSP1₄₂ in plants by synthesizing a plant-optimized MSP1₄₂ cDNA and either targeting the recombinant protein to protein storage vacuoles or fusing it with a stable plant storage protein. An exceptional improvement in MSP1₄₂ expression, from an undetectable level to 5% of total extractable protein, was achieved with these combined strategies. Importantly, the plant-derived MSP1₄₂ 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.
Lau
On Sun
OS
Department of Biology, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
Ng
Danny W-K
DW
Chan
Wendy W L
WW
Chang
Sandra P
SP
Sun
Samuel S M
SS
D000818:Animals; D017360:Arabidopsis / Q000235:genetics / Q000378:metabolism*; D017780:Malaria Vaccines / Q000276:immunology*; D020066:Merozoite Surface Protein 1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D012639:Seeds / Q000235:genetics / Q000378:metabolism*
D017780:Malaria Vaccines; D020066:Merozoite Surface Protein 1