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

Camila Tenorio França | Michael T White | Wen-Qiang He | Jessica B Hostetler | Jessica Brewster | Gabriel Frato | Indu Malhotra | Jakub Gruszczyk | Christele Huon | Enmoore Lin | Benson Kiniboro | Anjali Yadava | Peter Siba | Mary R Galinski | Julie Healer | Chetan Chitnis | Alan F Cowman | Eizo Takashima | Takafumi Tsuboi | Wai-Hong Tham | Rick M Fairhurst | Julian C Rayner | Christopher L King | Ivo Mueller
eLife | 2017

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.

Pubmed ID: 28949293

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Associated grants

  • Agency: Medical Research Council, United Kingdom
    Id: MR/J002283/1
  • Agency: NIH HHS, United States
    Id: P51 OD011132
  • Agency: Wellcome Trust, United Kingdom
    Id: 208693/Z/17/Z
  • Agency: Medical Research Council, United Kingdom
    Id: MR/L012170/1
  • Agency: NIAID NIH HHS, United States
    Id: U19 AI089686
  • Agency: Wellcome Trust, United Kingdom
    Id: 098051

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RAMA (tool)

RRID:SCR_001358

Software package for robust estimation of cDNA microarray intensities with replicates. It uses a Bayesian hierarchical model for the robust estimation. Outliers are modeled explicitly using a t-distribution, and the model also addresses classical issues such as design effects, normalization, transformation, and nonconstant variance.

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Yerkes National Primate Research Center (tool)

RRID:SCR_001914

Center for advancing scientific understanding and improving the health and well-being of humans and nonhuman primates. The Center conducts research in microbiology and immunology, neurologic diseases, neuropharmacology, behavioral, cognitive and developmental neuroscience, and psychiatric disorders.

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