Identification of highly-protective combinations of Plasmodium vivax recombinant proteins for vaccine development
- Walter and Eliza Hall Institute of Medical Research, Australia
- University of Melbourne, Australia
- Wellcome Trust Sanger Institute, United Kingdom
- Case Western Reserve University, United States
- Institut Pasteur, France
- Papua New Guinea Institute of Medical Research, Papua New Guinea
- Walter Reed Army Institute of Research, United States
- Emory University, United States
- Ehime University, Japan
- National Institute of Allergy and Infectious Diseases, National Institutes of Health, United States
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.
Article and author information
Author details
Camila Tenorio França
Funding
National Institutes of Health (U19AI089686)
- Ivo Mueller
Japan Society for the Promotion of Science (JP26253026)
- Takafumi Tsuboi
Japan Society for the Promotion of Science (JP15H05276)
- Takafumi Tsuboi
Japan Society for the Promotion of Science (JP16K15266)
- Takafumi Tsuboi
National Health and Medical Research Council (Independent Research Institute Infrastructure Support Scheme)
- Ivo Mueller
University of Melbourne (Melbourne International Postgraduate Scholarship)
- Camila Tenorio França
University of Melbourne (Melbourne International Postgraduate Scholarship)
- Wen-Qiang He
Australian Research Council (Australian Research Council Future Fellowship)
- Wai-Hong Tham
National Health and Medical Research Council (Senior Research Fellowship 1043345)
- Ivo Mueller
National Institute of Allergy and Infectious Diseases (Intramural Research Program)
- Rick M Fairhurst
National Institutes of Health (AI063135)
- Rick M Fairhurst
National Health and Medical Research Council (1021544)
- Ivo Mueller
National Health and Medical Research Council (1092789)
- Alan F Cowman
Malaria Elimination Science Alliance
- Ivo Mueller
Wellcome (98051)
- Julian C Rayner
Medical Research Council (MR/J002283/1)
- Julian C Rayner
Medical Research Council (MR/L012170/1)
- Julian C Rayner
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Department of Health and Human Services, Department of the Army, the Department of Defense, nor the U.S. Government.
Ethics
Human subjects: Ethical clearance for this study was obtained from the Medical Research and Advisory Committee of the Ministry of Health in PNG (MRAC 05.19), and the Walter and Eliza Hall Institute (HREC 07/07). Written informed consent was obtained from the parents or guardians of all children participating in the PNG cohort study prior to enrollment.
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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Identification of highly-protective combinations of Plasmodium vivax recombinant proteins for vaccine development
eLife 6:e28673.
https://doi.org/10.7554/eLife.28673
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Results: Twenty-eight top-ranked metabolites were included in linear regression models adjusted for the child's nutritional status, diet quality, and infant age. Cresol sulfate (β = -0.07; adjusted-p < 0.001), hippuric acid (β = -0.06; adjusted-p < 0.001), phenylacetylglutamine (β = -0.06; adjusted-p < 0.001), and trimethylamine-N-oxide (β = -0.05; adjusted-p = 0.002) showed inverse associations with DQ. We observed opposite directions in the association of DQ for creatinine (for children aged -1 SD: β = -0.05; p =0.01; +1 SD: β = 0.05; p =0.02) and methylhistidine (-1 SD: β = - 0.04; p =0.04; +1 SD: β = 0.04; p =0.03).
Conclusion: Serum biomarkers, including dietary and microbial-derived metabolites involved in the gut-brain axis, may potentially be used to track children at risk for developmental delays.
Funding: Supported by the Brazilian Ministry of Health and the Brazilian National Research Council.
