This site needs JavaScript to work properly. Please enable it to take advantage of the complete set of features!
Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

NIH NLM Logo
Log in
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Feb 15;13(2):e0006987.
doi: 10.1371/journal.pntd.0006987. eCollection 2019 Feb.

Antibody responses to Plasmodium vivax Duffy binding and Erythrocyte binding proteins predict risk of infection and are associated with protection from clinical Malaria

Affiliations

Antibody responses to Plasmodium vivax Duffy binding and Erythrocyte binding proteins predict risk of infection and are associated with protection from clinical Malaria

Wen-Qiang He et al. PLoS Negl Trop Dis. .

Abstract

Background: The Plasmodium vivax Duffy Binding Protein (PvDBP) is a key target of naturally acquired immunity. However, region II of PvDBP, which contains the receptor-binding site, is highly polymorphic. The natural acquisition of antibodies to different variants of PvDBP region II (PvDBPII), including the AH, O, P and Sal1 alleles, the central region III-V (PvDBPIII-V), and P. vivax Erythrocyte Binding Protein region II (PvEBPII) and their associations with risk of clinical P. vivax malaria are not well understood.

Methodology: Total IgG and IgG subclasses 1, 2, and 3 that recognize four alleles of PvDBPII (AH, O, P, and Sal1), PvDBPIII-V and PvEBPII were measured in samples collected from a cohort of 1 to 3 year old Papua New Guinean (PNG) children living in a highly endemic area of PNG. The levels of binding inhibitory antibodies (BIAbs) to PvDBPII (AH, O, and Sal1) were also tested in a subset of children. The association of presence of IgG with age, cumulative exposure (measured as the product of age and malaria infections during follow-up) and prospective risk of clinical malaria were evaluated.

Results: The increase in antigen-specific total IgG, IgG1, and IgG3 with age and cumulative exposure was only observed for PvDBPII AH and PvEBPII. High levels of total IgG and predominant subclass IgG3 specific for PvDBPII AH were associated with decreased incidence of clinical P. vivax episodes (aIRR = 0.56-0.68, P≤0.001-0.021). High levels of total IgG and IgG1 to PvEBPII correlated strongly with protection against clinical vivax malaria compared with IgGs against all PvDBPII variants (aIRR = 0.38, P<0.001). Antibodies to PvDBPII AH and PvEBPII showed evidence of an additive effect, with a joint protective association of 70%.

Conclusion: Antibodies to the key parasite invasion ligands PvDBPII and PvEBPII are good correlates of protection against P. vivax malaria in PNG. This further strengthens the rationale for inclusion of PvDBPII in a recombinant subunit vaccine for P. vivax malaria and highlights the need for further functional studies to determine the potential of PvEBPII as a component of a subunit vaccine for P. vivax malaria.

PubMed Disclaimer

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Heat map representation of the correlation between total and IgG subclass responses to PvDBPII variants and PvEBPII at enrolment.
The heat map colors correspond to the Spearman correlation coefficient and range from 0 (no correlation, blue) to 1 (strong correlation, yellow). P<0.001–0.899.
Fig 2
Fig 2
Distribution of antibody responses by the presence of malaria infection (A) and age (B). The X-axis represented log10 transformed antibody responses and the Y-axis represented the observed distribution of the antibody responses. Individuals without infection were shown in red and with infection in blue. Infection was determined by PCR at enrollment (A). Children were categorized into < 21 months of age (n = 112) and ≥ 21 months of age (n = 112) (B). P values were calculated using Wilcoxon-signed rank test. P<0.05 was considered significant.
Fig 3
Fig 3. Association between total and IgG subclasses to four PvDBPII variants, PvEBPII and protection against clinical malaria (density>500 parasite/ul) in 224 young Papua New Guinean children.
Data were plotted as exposure (molFOB), age, season and village of residency adjusted incidence rate ratios and 95% confidence intervals. Incidence rate ratios, 95% confidence intervals and P-values from GEE models. P<0.05 were deemed significant. * denotes P<0.05, ** denotes P<0.01, *** denotes P<0.001.
Fig 4
Fig 4. Gerbich blood type correlates with stronger antibody responses for PvDBPII variants.
The overall differences among three groups by red blood cell phenotype were compared using Kruskal-Wallis one-way analysis, and individual comparison of each two groups was tested by Wilcoxon signed-rank sum method, star represents the comparison to wild-type group. P<0.05 were deemed significant. * denotes P<0.05, ** denotes P<0.01, *** denotes P<0.001.

References

    1. Howes RE, Battle KE, Mendis KN, Smith DL, Cibulskis RE, Baird JK, et al. Global Epidemiology of Plasmodium vivax. The American journal of tropical medicine and hygiene. 2016;95(6 Suppl):15–34. 10.4269/ajtmh.16-0141 - DOI - PMC - PubMed
    1. Mueller I, Galinski MR, Baird JK, Carlton JM, Kochar DK, Alonso PL, et al. Key gaps in the knowledge of Plasmodium vivax, a neglected human malaria parasite. Lancet Infect Dis. 2009;9(9):555–66. 10.1016/S1473-3099(09)70177-X - DOI - PubMed
    1. Uthman OA, Graves PM, Saunders R, Gelband H, Richardson M, Garner P. Safety of primaquine given to people with G6PD deficiency: systematic review of prospective studies. Malar J. 2017;16(1):346 10.1186/s12936-017-1989-3 - DOI - PMC - PubMed
    1. Baird K. Origins and implications of neglect of G6PD deficiency and primaquine toxicity in Plasmodium vivax malaria. Pathogens and global health. 2015;109(3):93–106. 10.1179/2047773215Y.0000000016 - DOI - PMC - PubMed
    1. Wampfler R, Hofmann NE, Karl S, Betuela I, Kinboro B, Lorry L, et al. Effects of liver-stage clearance by Primaquine on gametocyte carriage of Plasmodium vivax and P. falciparum. PLOS Negl Trop Dis. 2017;11(7):e0005753 10.1371/journal.pntd.0005753 - DOI - PMC - PubMed

Publication types

LinkOut - more resources

Full text links
Public Library of Science full text link Public Library of Science Free PMC article
Cite

AltStyle によって変換されたページ (->オリジナル) /