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.
Reviewing Editor
- Urszula Krzych, Walter Reed Army Institute of Research, United States
Publication history
- Received: May 16, 2017
- Accepted: September 25, 2017
- Accepted Manuscript published: September 26, 2017 (version 1)
- Version of Record published: October 24, 2017 (version 2)
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.
Metrics
-
- 2,243
- Page views
-
- 446
- Downloads
-
- 34
- Citations
Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, PubMed Central.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Identification of highly-protective combinations of Plasmodium vivax recombinant proteins for vaccine development
eLife 6:e28673.
https://doi.org/10.7554/eLife.28673
Further reading
-
- Epidemiology and Global Health
- Evolutionary Biology
Mobile genetic elements (MGEs) are agents of horizontal gene transfer in bacteria, but can also be vertically inherited by daughter cells. Establishing the dynamics that led to contemporary patterns of MGEs in bacterial genomes is central to predicting the emergence and evolution of novel and resistant pathogens. Methicillin-resistant Staphylococcus aureus (MRSA) clonal-complex (CC) 398 is the dominant MRSA in European livestock and a growing cause of human infections. Previous studies have identified three categories of MGEs whose presence or absence distinguishes livestock-associated CC398 from a closely related and less antibiotic-resistant human-associated population. Here, we fully characterise the evolutionary dynamics of these MGEs using a collection of 1180 CC398 genomes, sampled from livestock and humans, over 27 years. We find that the emergence of livestock-associated CC398 coincided with the acquisition of a Tn916 transposon carrying a tetracycline resistance gene, which has been stably inherited for 57 years. This was followed by the acquisition of a type V SCCmec that carries methicillin, tetracycline, and heavy metal resistance genes, which has been maintained for 35 years, with occasional truncations and replacements with type IV SCCmec. In contrast, a class of prophages that carry a human immune evasion gene cluster and that are largely absent from livestock-associated CC398 have been repeatedly gained and lost in both human- and livestock-associated CC398. These contrasting dynamics mean that when livestock-associated MRSA is transmitted to humans, adaptation to the human host outpaces loss of antibiotic resistance. In addition, the stable inheritance of resistance-associated MGEs suggests that the impact of ongoing reductions in antibiotic and zinc oxide use in European farms on livestock-associated MRSA will be slow to be realised.
-
- Epidemiology and Global Health
In Spring 2021, the highly transmissible SARS-CoV-2 Delta variant began to cause increases in cases, hospitalizations, and deaths in parts of the United States. At the time, with slowed vaccination uptake, this novel variant was expected to increase the risk of pandemic resurgence in the US in summer and fall 2021. As part of the COVID-19 Scenario Modeling Hub, an ensemble of nine mechanistic models produced 6-month scenario projections for July–December 2021 for the United States. These projections estimated substantial resurgences of COVID-19 across the US resulting from the more transmissible Delta variant, projected to occur across most of the US, coinciding with school and business reopening. The scenarios revealed that reaching higher vaccine coverage in July–December 2021 reduced the size and duration of the projected resurgence substantially, with the expected impacts was largely concentrated in a subset of states with lower vaccination coverage. Despite accurate projection of COVID-19 surges occurring and timing, the magnitude was substantially underestimated 2021 by the models compared with the of the reported cases, hospitalizations, and deaths occurring during July–December, highlighting the continued challenges to predict the evolving COVID-19 pandemic. Vaccination uptake remains critical to limiting transmission and disease, particularly in states with lower vaccination coverage. Higher vaccination goals at the onset of the surge of the new variant were estimated to avert over 1.5 million cases and 21,000 deaths, although may have had even greater impacts, considering the underestimated resurgence magnitude from the model.
