Abstract
Development of effective malaria vaccines is hampered by the problem of producing correctly folded Plasmodium proteins for use as vaccine components. We have investigated the use of a novel ciliate expression system, Tetrahymena thermophila, as a P. falciparum vaccine antigen platform. A synthetic vaccine antigen composed of N-terminal and C-terminal regions of merozoite surface protein-1 (MSP-1) was expressed in Tetrahymena thermophila. The recombinant antigen was secreted into the culture medium and purified by monoclonal antibody (mAb) affinity chromatography. The vaccine was immunogenic in MF1 mice, eliciting high antibody titers against both N- and C-terminal components. Sera from immunized animals reacted strongly with P. falciparum parasites from three antigenically different strains by immunofluorescence assays, confirming that the antibodies produced are able to recognize parasite antigens in their native form. Epitope mapping of serum reactivity with a peptide library derived from all three MSP-1 Block 2 serotypes confirmed that the MSP-1 Block 2 hybrid component of the vaccine had effectively targeted all three serotypes of this polymorphic region of MSP-1. This study has successfully demonstrated the use of Tetrahymena thermophila as a recombinant protein expression platform for the production of malaria vaccine antigens.
Highlights
Malaria continues to be a major public health challenge, among children and pregnant women in sub-Saharan Africa [1]
The production of Plasmodium proteins for use in subunit vaccines using heterologous expression systems presents a number of challenges, since efficient expression of correctly folded proteins may be precluded by the inherent characteristics of many P. falciparum genes and their products, such as repetitive sequence content, large open reading frames, complex disulfide bonding patterns and the high AT content of P. falciparum DNA [10,11]
In this study we investigated the use of a promising protozoan protein expression system similar to Plasmodium falciparum parasite’s own biosynthetic machinery
Summary
Malaria continues to be a major public health challenge, among children and pregnant women in sub-Saharan Africa [1]. In light of the continuing emergence of drug-resistant strains of Plasmodium falciparum, there is a pressing need for effective vaccines against malaria [2]. There are a limited number of candidate malaria vaccine antigens in various stages of development, from early proof-ofconcept studies to late-phase clinical trials [3,4]. An extensive array of expression platforms have been used to generate vaccine antigens against malaria, including synthetic peptides, viral delivery systems, bacteria, transgenic plants or animals, insect cells, mammalian cell lines and yeast [5,6,7,8,9]. In this study we investigated the use of a promising protozoan protein expression system similar to Plasmodium falciparum parasite’s own biosynthetic machinery
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