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>Biochemical and Immunological Characterization of Bacterially Expressed and Refolded Plasmodium falciparum 42-Kilodalton C-Terminal Merozoite Surface Protein 1
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Biochemical and Immunological Characterization of Bacterially Expressed and Refolded Plasmodium falciparum 42-Kilodalton C-Terminal Merozoite Surface Protein 1
Protection against Plasmodium falciparum can be induced by vaccination in animal models with merozoite surface protein 1 (MSP1), which makes this protein an attractive vaccine candidate for malaria. In an attempt to produce a product that is easily scaleable and inexpensive, we expressed the C-terminal 42 kDa of MSP1 (MSP1 42 ) in Escherichia coli , refolded the protein to its native form from insoluble inclusion bodies, and tested its ability to elicit antibodies with in vitro and in vivo activities. Biochemical, biophysical, and immunological characterization confirmed that refolded E. coli MSP1 42 was homogeneous and highly immunogenic. In a formulation suitable for human use, rabbit antibodies were raised against refolded E. coli MSP1 42 and tested in vitro in a P. falciparum growth invasion assay. The antibodies inhibited the growth of parasites expressing either homologous or heterologous forms of P. falciparum MSP1 42 . However, the inhibitory activity was primarily a consequence of antibodies directed against the C- terminal 19 kDa of MSP1 (MSP1 19 ). Vaccination of nonhuman primates with E. coli MSP1 42 in Freund's adjuvant protected six of seven Aotus monkeys from virulent infection with P. falciparum . The protection correlated with antibody-dependent mechanisms. Thus, this new construct, E. coli MSP1 42 , is a viable candidate for human vaccine trials.
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