Abstract
Malaria represents a major public health problem and an important cause of mortality and morbidity. The malaria parasites are becoming resistant to drugs used to treat the disease and still no efficient vaccine has been developed. One promising vaccine candidate is the merozoite surface protein 1 (MSP1), which has been extensively investigated as a vaccine target. The surface protein MSP1 plays an essential role in the erythrocyte invasion process and is an accessible target for the immune system. Antibodies to the carboxy-terminal region of the protein, named MSP119, can inhibit erythrocyte invasion and parasite growth. In order to develop an effective MSP119- based vaccine against malaria, production of an antigen that is recognized by protective antibodies is mandatory. To this aim, we propose a method to produce the disulfide-rich MSP119 in its native conformation based on its in vitro oxidative refolding. The native conformation of the renatured MSP119 is carefully established by immunochemical reactivity experiments, circular dichroism and NMR. MSP119 can successfully be refolded in vitro as an isolated protein or as a fusion with the maltose binding protein. The possibility to properly fold MSP119 in vitro paves the way to new approaches for high titer production of native MSP119 using Escherichia coli as a host.
Highlights
Plasmodium falciparum is the major cause of human malaria, an endemic disease that can quickly become life threatening if not treated
The merozoite surface protein 1 (MSP1) is the most abundant protein on the surface of P. falciparum merozoites [3] and is one of the best characterized of many proteins on the merozoite surface that are being targeted for malaria vaccine development [4,5]
Obtention of F19 Fragments Seventeen mg of pure maltose binding protein (MBP)-F19 containing ca. 4 mg of F19ec were obtained per liter of bacterial culture
Summary
Plasmodium falciparum is the major cause of human malaria, an endemic disease that can quickly become life threatening if not treated. The World Health Organization estimates that malaria causes 300 to 500 million infections and over 1 million deaths each year almost exclusively among young children and pregnant women [1] Antimalarial treatments such as artemisinin combination therapies are widely used against Plasmodium falciparum infections, the parasites have developed resistance to a number of malaria drugs and there is a need to develop an effective vaccine. The protein is synthesized in schizonts as a ,190 kDa glycosylphosphatidylinositol (GPI) anchored protein that is processed by P. falciparum subtilisin 1 at the end of the schizogony into four polypeptides named p83, p42, p38 and p30 These fragments remain associated together on the parasite’s surface [6]. The F19 fragment is one of the most promising antigens for a malaria vaccine and it has been used in the attempt for developing multi-antigen vaccines that are based on the fusion of multiple epitopes [11]
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