A novel malaria vaccine candidate antigen expressed in Tetrahymena thermophila.
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.
Institute of Immunology and Infection Research, Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh, United Kingdom.
Graeme J M
GJ
Cowan
Cilian AG, Münster, Germany.
Ulrike
U
Bockau
Cilian AG, Münster, Germany.
Janna
J
Eleni-Muus
Cilian AG, Münster, Germany.
Ingo
I
Aldag
Cell Therapy Group, Scottish National Blood Transfusion Service, Edinburgh, United Kingdom.
Kay
K
Samuel
Institute of Immunology and Infection Research, Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh, United Kingdom.
Alison M
AM
Creasey
Cilian AG, Münster, Germany.
Marcus W W
MW
Hartmann
Institute of Immunology and Infection Research, Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh, United Kingdom.
David R
DR
Cavanagh
D000818:Animals; D021461:Animals, Outbred Strains; D000913:Antibodies, Protozoan / Q000097:blood; D018604:Epitope Mapping; D005260:Female; D006801:Humans; D017780:Malaria Vaccines / Q000096:biosynthesis* / Q000276:immunology; D016778:Malaria, Falciparum / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D020066:Merozoite Surface Protein 1 / Q000096:biosynthesis* / Q000276:immunology; D051379:Mice; D010963:Plasmodium falciparum / Q000276:immunology; D016808:Tetrahymena thermophila / Q000378:metabolism*; D014611:Vaccination; D064166:Vaccine Potency
D000913:Antibodies, Protozoan; D017780:Malaria Vaccines; D020066:Merozoite Surface Protein 1