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Clin. Vaccine Immunol. doi:10.1128/CVI.00172-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Comparative testing of six Plasmodium falciparum merozoite stage antigen-based malaria vaccine candidates

Centre for Medical Parasitology, Institute for International Health, Immunology & Microbiology, University of Copenhagen, ster Farimagsgade 5, bygning 22 & 23, Postboks 2099, 1014 Copenhagen K, Denmark; Institute of Immunology & Infection Research, Division of Biological Sciences, Ashworth Laboratories, University of Edinburgh, King's Buildings, West Mains Road, Edinburgh EH9 3JT, UK; Biomedical Primate Research Centre, Department of Parasitology, Lange Kleiweg 1339, 2288 GJ Rijswijk, The Netherlands; Division of Parasitology, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA UK; Institut Pasteur, Rue du Dr. Roux, Paris, France

^* To whom correspondence should be addressed. Email: d.e.arnot{at}cmp.dk.

	Abstract

Immunogenicity testing of Plasmodium falciparum antigens being considered as malaria vaccine candidates was undertaken in rabbits. The antigens compared were recombinant baculovirus MSP-1₁₉ and five Pichia pastoris candidates, including two versions of MSP-1₁₉, AMA-1 (domains I-II), AMA-1+MSP-1₁₉, and fused AMA-1-MSP-1₁₉). Animals were immunized with equimolar amounts of each antigen, formulated in Montanide ISA720. Specificities and titers of antibodies were compared using immuno-fluorescence assays (IFA) and ELISA. Anti-parasite activity of IgG in in vitro cultures was determined by growth inhibition assays (GIA), flow cytometry, lactate dehydrogenase assay and microscopy.

Baculovirus MSP-1₁₉ immunizations produced the highest parasite-specific antibody titers in IFA assays. In ELISA assays, baculovirus-produced MSP-1₁₉ induced more antibodies than any other single MSP-1₁₉ immunogen, and three times more MSP-1₁₉ specific antibodies than the AMA-1-MSP-1₁₉ fusion. Antibodies induced by baculovirus MSP-1₁₉ gave the highest levels of growth inhibition in HB3 and 3D7 parasite cultures, followed by AMA-1+MSP-1₁₉ and the AMA-1/MSP-1₁₉ fusion. With the FCR3 isolate (homologous to the AMA-1 construct), antibodies to the three AMA-1-containing candidates gave the highest levels of growth inhibition at high IgG concentrations, but antibodies to baculovirus MSP-1₁₉ inhibited as well or better at lower IgG concentrations. The two Pichia pastoris- produced MSP-1₁₉–induced IgGs conferred the lowest growth inhibition.

Comparative analysis of immunogenicity of vaccine antigens can be used to prioritize candidates before moving to expensive GMP production and clinical testing. The assays used have given discriminating readouts but it is not known whether any of them accurately reflect clinical protection.