title: New antigens for a multicomponent blood-stage malaria vaccine.
abstract: An effective blood-stage vaccine against Plasmodium falciparum remains a research priority, but the number of antigens that have been translated into multicomponent vaccines for testing in clinical trials remains limited. Investigating the large number of potential targets found in the parasite proteome has been constrained by an inability to produce natively folded recombinant antigens for immunological studies. We overcame these constraints by generating a large library of biochemically active merozoite surface and secreted full-length ectodomain proteins. We then systematically examined the antibody reactivity against these proteins in a cohort of Kenyan children (n = 286) who were sampled at the start of a malaria transmission season and prospectively monitored for clinical episodes of malaria over the ensuing 6 months. We found that antibodies to previously untested or little-studied proteins had superior or equivalent potential protective efficacy to the handful of current leading malaria vaccine candidates. Moreover, cumulative responses to combinations comprising 5 of the 10 top-ranked antigens, including PF3D7_1136200, MSP2, RhopH3, P41, MSP11, MSP3, PF3D7_0606800, AMA1, Pf113, and MSRP1, were associated with 100% protection against clinical episodes of malaria. These data suggest not only that there are many more potential antigen candidates for the malaria vaccine development pipeline but also that effective vaccination may be achieved by combining a selection of these antigens.
authors: Pathogen Vector and Human Biology Department, Kenya Medical Research Institute Centre for Geographical Medicine Research, Coast, P. O. Box 230, 80108 Kilifi, Kenya.
authors: Faith H
authors: FH
authors: Osier
authors: Pathogen Vector and Human Biology Department, Kenya Medical Research Institute Centre for Geographical Medicine Research, Coast, P. O. Box 230, 80108 Kilifi, Kenya.
authors: Margaret J
authors: MJ
authors: Mackinnon
authors: Cell Surface Signalling Laboratory, Wellcome Trust Sanger Institute, Cambridge CB10 1HH, UK. Malaria Programme, Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK.
authors: Cécile
authors: C
authors: Crosnier
authors: Pathogen Vector and Human Biology Department, Kenya Medical Research Institute Centre for Geographical Medicine Research, Coast, P. O. Box 230, 80108 Kilifi, Kenya.
authors: Gregory
authors: G
authors: Fegan
authors: Pathogen Vector and Human Biology Department, Kenya Medical Research Institute Centre for Geographical Medicine Research, Coast, P. O. Box 230, 80108 Kilifi, Kenya.
authors: Gathoni
authors: G
authors: Kamuyu
authors: Cell Surface Signalling Laboratory, Wellcome Trust Sanger Institute, Cambridge CB10 1HH, UK. Malaria Programme, Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK.
authors: Madushi
authors: M
authors: Wanaguru
authors: Pathogen Vector and Human Biology Department, Kenya Medical Research Institute Centre for Geographical Medicine Research, Coast, P. O. Box 230, 80108 Kilifi, Kenya.
authors: Edna
authors: E
authors: Ogada
authors: Cell Surface Signalling Laboratory, Wellcome Trust Sanger Institute, Cambridge CB10 1HH, UK.
authors: Brian
authors: B
authors: McDade
authors: Malaria Programme, Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK.
authors: Julian C
authors: JC
authors: Rayner
authors: Cell Surface Signalling Laboratory, Wellcome Trust Sanger Institute, Cambridge CB10 1HH, UK. Malaria Programme, Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK.
authors: Gavin J
authors: GJ
authors: Wright
authors: Pathogen Vector and Human Biology Department, Kenya Medical Research Institute Centre for Geographical Medicine Research, Coast, P. O. Box 230, 80108 Kilifi, Kenya. KMarsh@kemri-wellcome.org.
authors: Kevin
authors: K
authors: Marsh
mesh_terms: D000367:Age Factors; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007630:Kenya / Q000453:epidemiology; D017780:Malaria Vaccines / Q000276:immunology*; D016778:Malaria, Falciparum / Q000097:blood / Q000453:epidemiology / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control* / Q000635:transmission; D052940:Merozoites / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D010963:Plasmodium falciparum / Q000276:immunology*; D011446:Prospective Studies; D015800:Protozoan Proteins / Q000276:immunology; D016036:Seroepidemiologic Studies; D013997:Time Factors
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D015415:Biomarkers; C506685:MSP3 protein, Plasmodium falciparum (181-276); D017780:Malaria Vaccines; D010446:Peptide Fragments; D015800:Protozoan Proteins; C065974:merozoite surface protein 2, Plasmodium; C065352:rhoptry associated protein, Plasmodium