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.
Metrics
-
- 2,699
- views
-
- 502
- downloads
-
- 65
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
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
Artificially sweetened beverages containing noncaloric monosaccharides were suggested as healthier alternatives to sugar-sweetened beverages. Nevertheless, the potential detrimental effects of these noncaloric monosaccharides on blood vessel function remain inadequately understood. We have established a zebrafish model that exhibits significant excessive angiogenesis induced by high glucose, resembling the hyperangiogenic characteristics observed in proliferative diabetic retinopathy (PDR). Utilizing this model, we observed that glucose and noncaloric monosaccharides could induce excessive formation of blood vessels, especially intersegmental vessels (ISVs). The excessively branched vessels were observed to be formed by ectopic activation of quiescent endothelial cells (ECs) into tip cells. Single-cell transcriptomic sequencing analysis of the ECs in the embryos exposed to high glucose revealed an augmented ratio of capillary ECs, proliferating ECs, and a series of upregulated proangiogenic genes. Further analysis and experiments validated that reduced foxo1a mediated the excessive angiogenesis induced by monosaccharides via upregulating the expression of marcksl1a. This study has provided new evidence showing the negative effects of noncaloric monosaccharides on the vascular system and the underlying mechanisms.
-
- Epidemiology and Global Health
- Microbiology and Infectious Disease
Influenza viruses continually evolve new antigenic variants, through mutations in epitopes of their major surface proteins, hemagglutinin (HA) and neuraminidase (NA). Antigenic drift potentiates the reinfection of previously infected individuals, but the contribution of this process to variability in annual epidemics is not well understood. Here, we link influenza A(H3N2) virus evolution to regional epidemic dynamics in the United States during 1997—2019. We integrate phenotypic measures of HA antigenic drift and sequence-based measures of HA and NA fitness to infer antigenic and genetic distances between viruses circulating in successive seasons. We estimate the magnitude, severity, timing, transmission rate, age-specific patterns, and subtype dominance of each regional outbreak and find that genetic distance based on broad sets of epitope sites is the strongest evolutionary predictor of A(H3N2) virus epidemiology. Increased HA and NA epitope distance between seasons correlates with larger, more intense epidemics, higher transmission, greater A(H3N2) subtype dominance, and a greater proportion of cases in adults relative to children, consistent with increased population susceptibility. Based on random forest models, A(H1N1) incidence impacts A(H3N2) epidemics to a greater extent than viral evolution, suggesting that subtype interference is a major driver of influenza A virus infection ynamics, presumably via heterosubtypic cross-immunity.
