title: An Antibody Screen of a Plasmodium vivax Antigen Library Identifies Novel Merozoite Proteins Associated with Clinical Protection.
abstract: Elimination of Plasmodium vivax malaria would be greatly facilitated by the development of an effective vaccine. A comprehensive and systematic characterization of antibodies to P. vivax antigens in exposed populations is useful in guiding rational vaccine design.
  
  
  
  In this study, we investigated antibodies to a large library of P. vivax entire ectodomain merozoite proteins in 2 Asia-Pacific populations, analysing the relationship of antibody levels with markers of current and cumulative malaria exposure, and socioeconomic and clinical indicators. 29 antigenic targets of natural immunity were identified. Of these, 12 highly-immunogenic proteins were strongly associated with age and thus cumulative lifetime exposure in Solomon Islanders (P<0.001-0.027). A subset of 6 proteins, selected on the basis of immunogenicity and expression levels, were used to examine antibody levels in plasma samples from a population of young Papua New Guinean children with well-characterized individual differences in exposure. This analysis identified a strong association between reduced risk of clinical disease and antibody levels to P12, P41, and a novel hypothetical protein that has not previously been studied, PVX_081550 (IRR 0.46-0.74; P<0.001-0.041).
  
  
  
  These data emphasize the benefits of an unbiased screening approach in identifying novel vaccine candidate antigens. Functional studies are now required to establish whether PVX_081550 is a key component of the naturally-acquired protective immune response, a biomarker of immune status, or both.
authors.affiliation: Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.|Department of Medical Biology, University of Melbourne, Melbourne, Australia.
authors.forename: Camila T
authors.initials: CT
authors.lastname: França
authors.affiliation: Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.|Malaria Programme, Wellcome Trust Sanger Institute, Hinxton, United Kingdom.
authors.forename: Jessica B
authors.initials: JB
authors.lastname: Hostetler
authors.affiliation: Malaria Programme, Wellcome Trust Sanger Institute, Hinxton, United Kingdom.
authors.forename: Sumana
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.|Center for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom.
authors.forename: Michael T
authors.initials: MT
authors.lastname: White
authors.affiliation: Vector Borne Diseases Unit, PNG Institute of Medical Research, Madang, Papua New Guinea.
authors.forename: Enmoore
authors.initials: E
authors.lastname: Lin
authors.affiliation: Vector Borne Diseases Unit, PNG Institute of Medical Research, Madang, Papua New Guinea.
authors.forename: Benson
authors.initials: B
authors.lastname: Kiniboro
authors.affiliation: Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.|Department of Medical Biology, University of Melbourne, Melbourne, Australia.
authors.forename: Andreea
authors.initials: A
authors.lastname: Waltmann
authors.affiliation: National Health Training & Research Institute, Ministry of Health, Honiara, Solomon Islands.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Darcy
authors.affiliation: Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.|Department of Medical Biology, University of Melbourne, Melbourne, Australia.
authors.forename: Connie S N
authors.initials: CS
authors.lastname: Li Wai Suen
authors.affiliation: Vector Borne Diseases Unit, PNG Institute of Medical Research, Madang, Papua New Guinea.
authors.forename: Peter
authors.initials: P
authors.lastname: Siba
authors.affiliation: Center for Global Health & Diseases, Case Western Reserve University, Cleveland, Ohio, United States of America.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: King
authors.affiliation: Malaria Programme, Wellcome Trust Sanger Institute, Hinxton, United Kingdom.
authors.forename: Julian C
authors.initials: JC
authors.lastname: Rayner
authors.affiliation: Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Rick M
authors.initials: RM
authors.lastname: Fairhurst
authors.affiliation: Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.|Department of Medical Biology, University of Melbourne, Melbourne, Australia.|ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Ivo
authors.initials: I
authors.lastname: Mueller
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology*; D000953:Antigens, Protozoan / Q000097:blood / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D002648:Child; D015331:Cohort Studies; D055808:Drug Discovery; D005260:Female; D057166:High-Throughput Screening Assays; D006801:Humans; D007113:Immunity, Innate; D007223:Infant; D016780:Malaria, Vivax / Q000453:epidemiology / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control*; D008542:Melanesia / Q000453:epidemiology; D052940:Merozoites / Q000737:chemistry* / Q000276:immunology; D008875:Middle Aged; D010219:Papua New Guinea / Q000453:epidemiology; D019151:Peptide Library; D010966:Plasmodium vivax / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D015800:Protozoan Proteins / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification; D055815:Young Adult
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D015415:Biomarkers; D019151:Peptide Library; D015800:Protozoan Proteins