High-level expression of the malaria blood-stage vaccine candidate Plasmodium falciparum apical membrane antigen 1 and induction of antibodies that inhibit erythrocyte invasion
Apical membrane antigen I (AMA-1) is a highly promising malaria blood-stage vaccine candidate that has induced protection in rodent and nonhuman primate models of malaria. Authentic conformation of the protein appears to be essential for the induction of parasite-inhibitory antibody responses. Here we have developed a synthetic gene with adapted codon usage to allow expression of Plasmodium falciparum FVO strain AMA-1 (PfAMA-1) in Pichia pastoris. In addition, potential N-glycosylation sites were changed, exploiting the lack of conservation of these sites in Plasmodium, to obtain high-level secretion of a homogeneous product, suitable for scale-up according to current good manufacturing procedures. Purified PfAMA-1 displayed authentic antigenic properties, indicating that the amino acid changes had no deleterious effect on the conformation of the protein. High-titer antibodies, raised in rabbits, reacted strongly with homologous and heterologous P.falciparum by immunofluorescence. In addition, purified immunoglobulin G from immunized animals strongly inhibited invasion of red blood cells by homologous and, to a somewhat lesser extent, heterologous P.falciparum.
机构:PO Royal Melbourne Hosp, Cooperat Res Ctr Vaccine Technol, Parkville, Vic 3050, Australia
Anders, RF
Crewther, PE
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机构:PO Royal Melbourne Hosp, Cooperat Res Ctr Vaccine Technol, Parkville, Vic 3050, Australia
Crewther, PE
Edwards, S
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PO Royal Melbourne Hosp, Cooperat Res Ctr Vaccine Technol, Parkville, Vic 3050, AustraliaPO Royal Melbourne Hosp, Cooperat Res Ctr Vaccine Technol, Parkville, Vic 3050, Australia
Edwards, S
Margetts, M
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机构:PO Royal Melbourne Hosp, Cooperat Res Ctr Vaccine Technol, Parkville, Vic 3050, Australia
Margetts, M
Matthew, MLSM
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机构:PO Royal Melbourne Hosp, Cooperat Res Ctr Vaccine Technol, Parkville, Vic 3050, Australia
Matthew, MLSM
Pollock, B
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机构:PO Royal Melbourne Hosp, Cooperat Res Ctr Vaccine Technol, Parkville, Vic 3050, Australia
Pollock, B
Pye, D
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机构:PO Royal Melbourne Hosp, Cooperat Res Ctr Vaccine Technol, Parkville, Vic 3050, Australia
机构:PO Royal Melbourne Hosp, Cooperat Res Ctr Vaccine Technol, Parkville, Vic 3050, Australia
Anders, RF
Crewther, PE
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h-index: 0
机构:PO Royal Melbourne Hosp, Cooperat Res Ctr Vaccine Technol, Parkville, Vic 3050, Australia
Crewther, PE
Edwards, S
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h-index: 0
机构:
PO Royal Melbourne Hosp, Cooperat Res Ctr Vaccine Technol, Parkville, Vic 3050, AustraliaPO Royal Melbourne Hosp, Cooperat Res Ctr Vaccine Technol, Parkville, Vic 3050, Australia
Edwards, S
Margetts, M
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h-index: 0
机构:PO Royal Melbourne Hosp, Cooperat Res Ctr Vaccine Technol, Parkville, Vic 3050, Australia
Margetts, M
Matthew, MLSM
论文数: 0引用数: 0
h-index: 0
机构:PO Royal Melbourne Hosp, Cooperat Res Ctr Vaccine Technol, Parkville, Vic 3050, Australia
Matthew, MLSM
Pollock, B
论文数: 0引用数: 0
h-index: 0
机构:PO Royal Melbourne Hosp, Cooperat Res Ctr Vaccine Technol, Parkville, Vic 3050, Australia
Pollock, B
Pye, D
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h-index: 0
机构:PO Royal Melbourne Hosp, Cooperat Res Ctr Vaccine Technol, Parkville, Vic 3050, Australia