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    Identification of highly-protective combinations of Plasmodium vivax recombinant proteins for vaccine development

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    Author
    Franca, CT; White, MT; He, W-Q; Hostetler, JB; Brewster, J; Frato, G; Malhotra, I; Gruszczyk, J; Huon, C; Lin, E; ...
    Date
    2017-09-26
    Source Title
    eLife
    Publisher
    ELIFE SCIENCES PUBLICATIONS LTD
    University of Melbourne Author/s
    Healer, Julie; Mueller, Ivo; Cowman, Alan; Tenorio Franca, Camila; Tham, Wai-Hong
    Affiliation
    Medical Biology (W.E.H.I.)
    Metadata
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    Document Type
    Journal Article
    Citations
    Franca, C. T., White, M. T., He, W. -Q., Hostetler, J. B., Brewster, J., Frato, G., Malhotra, I., Gruszczyk, J., Huon, C., Lin, E., Kiniboro, B., Yadava, A., Siba, P., Galinski, M. R., Healer, J., Chitnis, C., Cowman, A. F., Takashima, E., Tsuboi, T. ,... Mueller, I. (2017). Identification of highly-protective combinations of Plasmodium vivax recombinant proteins for vaccine development. ELIFE, 6, https://doi.org/10.7554/eLife.28673.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/255286
    DOI
    10.7554/eLife.28673
    Abstract
    The study of antigenic targets of naturally-acquired immunity is essential to identify and prioritize antigens for further functional characterization. We measured total IgG antibodies to 38 P. vivax antigens, investigating their relationship with prospective risk of malaria in a cohort of 1-3 years old Papua New Guinean children. Using simulated annealing algorithms, the potential protective efficacy of antibodies to multiple antigen-combinations, and the antibody thresholds associated with protection were investigated for the first time. High antibody levels to multiple known and newly identified proteins were strongly associated with protection (IRR 0.44-0.74, p<0.001-0.041). Among five-antigen combinations with the strongest protective effect (>90%), EBP, DBPII, RBP1a, CyRPA, and PVX_081550 were most frequently identified; several of them requiring very low antibody levels to show a protective association. These data identify individual antigens that should be prioritized for further functional testing and establish a clear path to testing a multicomponent P. vivax vaccine.

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