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dc.contributor.authorFinney, Olivia C.
dc.contributor.authorDanziger, Samuel A.
dc.contributor.authorMolina, Douglas M.
dc.contributor.authorVignali, Marissa
dc.contributor.authorTakagi, Aki
dc.contributor.authorJi, Ming
dc.contributor.authorStanisic, Danielle I.
dc.contributor.authorSiba, Peter M.
dc.contributor.authorLiang, Xiawu
dc.contributor.authorAitchison, John D.
dc.contributor.authorMueller, Ivo
dc.contributor.authorGardner, Malcolm J.
dc.contributor.authorWang, Ruobing
dc.date.accessioned2019-02-15T12:32:53Z
dc.date.available2019-02-15T12:32:53Z
dc.date.issued2014
dc.identifier.issn1535-9476
dc.identifier.doi10.1074/mcp.M113.036632
dc.identifier.urihttp://hdl.handle.net/10072/166006
dc.description.abstractMalaria remains one of the most prevalent and lethal human infectious diseases worldwide. A comprehensive characterization of antibody responses to blood stage malaria is essential to support the development of future vaccines, sero-diagnostic tests, and sero-surveillance methods. We constructed a proteome array containing 4441 recombinant proteins expressed by the blood stages of the two most common human malaria parasites, P. falciparum (Pf) and P. vivax (Pv), and used this array to screen sera of Papua New Guinea children infected with Pf, Pv, or both (Pf/Pv) that were either symptomatic (febrile), or asymptomatic but had parasitemia detectable via microscopy or PCR. We hypothesized that asymptomatic children would develop antigen-specific antibody profiles associated with antidisease immunity, as compared with symptomatic children. The sera from these children recognized hundreds of the arrayed recombinant Pf and Pv proteins. In general, responses in asymptomatic children were highest in those with high parasitemia, suggesting that antibody levels are associated with parasite burden. In contrast, symptomatic children carried fewer antibodies than asymptomatic children with infections detectable by microscopy, particularly in Pv and Pf/Pv groups, suggesting that antibody production may be impaired during symptomatic infections. We used machine-learning algorithms to investigate the relationship between antibody responses and symptoms, and we identified antibody responses to sets of Plasmodium proteins that could predict clinical status of the donors. Several of these antibody responses were identified by multiple comparisons, including those against members of the serine enriched repeat antigen family and merozoite protein 4. Interestingly, both P. falciparum serine enriched repeat antigen-5 and merozoite protein 4 have been previously investigated for use in vaccines. This machine learning approach, never previously applied to proteome arrays, can be used to generate a list of potential seroprotective and/or diagnostic antigens candidates that can be further evaluated in longitudinal studies.
dc.description.peerreviewedYes
dc.languageEnglish
dc.publisherAmerican Society for Biochemistry and Molecular Biology
dc.publisher.placeUnited States
dc.relation.ispartofpagefrom2646
dc.relation.ispartofpageto2660
dc.relation.ispartofissue10
dc.relation.ispartofjournalMolecular and Cellular Proteomics
dc.relation.ispartofvolume13
dc.subject.fieldofresearchMedical Parasitology
dc.subject.fieldofresearchcode110803
dc.titlePredicting antidisease immunity using proteome arrays and sera from children naturally exposed to malaria
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dc.description.versionPublished
gro.rights.copyright© The American Society for Biochemistry and Molecular Biology. This research was originally published in Molecular & Cellular Proteomics (MCP). Finney et. al., Predicting anti-disease immunity using proteome arrays and sera from children naturally exposed to malaria Molecular & Cellular Proteomics (MCP), 13 (10) 2646-2660. Reproduced in accordance with the copyright policy of the publisher. Please refer to the journal's website for access to the definitive version.
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gro.griffith.authorStanisic, Danielle


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