Biochemical and Immunological Characterization of Bacterially Expressed and RefoldedPlasmodium falciparum42-Kilodalton C-Terminal Merozoite Surface Protein 1

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Abstract
Protection againstPlasmodium falciparumcan 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 (MSP142) inEscherichia 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 refoldedE. coliMSP142was homogeneous and highly immunogenic. In a formulation suitable for human use, rabbit antibodies were raised against refoldedE. coliMSP142and tested in vitro in aP. falciparumgrowth invasion assay. The antibodies inhibited the growth of parasites expressing either homologous or heterologous forms ofP. falciparumMSP142. However, the inhibitory activity was primarily a consequence of antibodies directed against the C- terminal 19 kDa of MSP1 (MSP119). Vaccination of nonhuman primates withE. coliMSP142in Freund's adjuvant protected six of sevenAotusmonkeys from virulent infection withP. falciparum. The protection correlated with antibody-dependent mechanisms. Thus, this new construct,E. coliMSP142, is a viable candidate for human vaccine trials.