title: A malaria vaccine based on the polymorphic block 2 region of MSP-1 that elicits a broad serotype-spanning immune response.
abstract: Polymorphic parasite antigens are known targets of protective immunity to malaria, but this antigenic variation poses challenges to vaccine development. A synthetic MSP-1 Block 2 construct, based on all polymorphic variants found in natural Plasmodium falciparum isolates has been designed, combined with the relatively conserved Block 1 sequence of MSP-1 and expressed in E.coli. The MSP-1 Hybrid antigen has been produced with high yield by fed-batch fermentation and purified without the aid of affinity tags resulting in a pure and extremely thermostable antigen preparation. MSP-1 hybrid is immunogenic in experimental animals using adjuvants suitable for human use, eliciting antibodies against epitopes from all three Block 2 serotypes. Human serum antibodies from Africans naturally exposed to malaria reacted to the MSP-1 hybrid as strongly as, or better than the same serum reactivities to individual MSP-1 Block 2 antigens, and these antibody responses showed clear associations with reduced incidence of malaria episodes. The MSP-1 hybrid is designed to induce a protective antibody response to the highly polymorphic Block 2 region of MSP-1, enhancing the repertoire of MSP-1 Block 2 antibody responses found among immune and semi-immune individuals in malaria endemic areas. The target population for such a vaccine is young children and vulnerable adults, to accelerate the acquisition of a full range of malaria protective antibodies against this polymorphic parasite antigen.
authors.affiliation: Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Graeme J M
authors.initials: GJ
authors.lastname: Cowan
authors.forename: Alison M
authors.initials: AM
authors.lastname: Creasey
authors.forename: Kelwalin
authors.initials: K
authors.lastname: Dhanasarnsombut
authors.forename: Alan W
authors.initials: AW
authors.lastname: Thomas
authors.forename: Edmond J
authors.initials: EJ
authors.lastname: Remarque
authors.forename: David R
authors.initials: DR
authors.lastname: Cavanagh
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000913:Antibodies, Protozoan / Q000097:blood* / Q000276:immunology*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007114:Immunization; D015151:Immunoblotting; D007074:Immunoglobulin G / Q000276:immunology*; D008253:Macaca mulatta; D017780:Malaria Vaccines / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology* / Q000517:prevention & control; D020066:Merozoite Surface Protein 1 / Q000276:immunology*; D051379:Mice; D008811:Mice, Inbred DBA; D010963:Plasmodium falciparum / Q000254:growth & development / Q000276:immunology*; D011817:Rabbits; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D000911:Antibodies, Monoclonal; D000913:Antibodies, Protozoan; D007074:Immunoglobulin G; D017780:Malaria Vaccines; D020066:Merozoite Surface Protein 1
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