Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Malaria Journal
Published in: Malaria Journal 1/2017

Open Access 01-12-2017 | Research

IgG antibodies to synthetic GPI are biomarkers of immune-status to both Plasmodium falciparum and Plasmodium vivax malaria in young children

Authors: Camila T. França, Connie S. N. Li Wai Suen, Amandine Carmagnac, Enmoore Lin, Benson Kiniboro, Peter Siba, Louis Schofield, Ivo Mueller

Published in: Malaria Journal | Issue 1/2017

Login to get access

Abstract

Background

Further reduction in malaria prevalence and its eventual elimination would be greatly facilitated by the development of biomarkers of exposure and/or acquired immunity to malaria, as well as the deployment of effective vaccines against Plasmodium falciparum and Plasmodium vivax. A better understanding of the acquisition of immunity in naturally-exposed populations is essential for the identification of antigens useful as biomarkers, as well as to inform rational vaccine development.

Methods

ELISA was used to measure total IgG to a synthetic form of glycosylphosphatidylinositol from P. falciparum (PfGPI) in a cohort of 1–3 years old Papua New Guinea children with well-characterized individual differences in exposure to P. falciparum and P. vivax blood-stage infections. The relationship between IgG levels to PfGPI and measures of recent and past exposure to P. falciparum and P. vivax infections was investigated, as well as the association between antibody levels and prospective risk of clinical malaria over 16 months of follow-up.

Results

Total IgG levels to PfGPI were low in the young children tested. Antibody levels were higher in the presence of P. falciparum or P. vivax infections, but short-lived. High IgG levels were associated with higher risk of P. falciparum malaria (IRR 1.33–1.66, P = 0.008–0.027), suggesting that they are biomarkers of increased exposure to P. falciparum infections. Given the cross-reactive nature of antibodies to PfGPI, high IgG levels were also associated with reduced risk of P. vivax malaria (IRR 0.65–0.67, P = 0.039–0.044), indicating that these antibodies are also markers of acquired immunity to P. vivax.

Conclusions

This study highlights that in young children, IgG to PfGPI might be a useful marker of immune-status to both P. falciparum and P. vivax infections, and potentially useful to help malaria control programs to identify populations at-risk. Further functional studies are necessary to confirm the potential of PfGPI as a target for vaccine development.
Appendix
Available only for authorised users
Literature
1.
WHO. World malaria report 2015. Geneva: World Health Organization; 2015.
2.
Tanner M, Greenwood B, Whitty CJ, Ansah EK, Price RN, Dondorp AM, et al. Malaria eradication and elimination: views on how to translate a vision into reality. BMC Med. 2015;13:167.CrossRefPubMedPubMedCentral
3.
Cotter C, Sturrock HJ, Hsiang MS, Liu J, Phillips AA, Hwang J, et al. The changing epidemiology of malaria elimination: new strategies for new challenges. Lancet. 2013;382:900–11.CrossRefPubMed
4.
King CL, Davies DH, Felgner P, Baum E, Jain A, Randall A, et al. Biosignatures of exposure/transmission and immunity. Am J Trop Med Hyg. 2015;93:16–27.CrossRefPubMedPubMedCentral
5.
Mueller I, Shakri AR, Chitnis CE. Development of vaccines for Plasmodium vivax malaria. Vaccine. 2015;33:7489–95.CrossRefPubMed
6.
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;9:555–66.CrossRefPubMed
7.
Stanisic DI, Fowkes FJ, Koinari M, Javati S, Lin E, Kiniboro B, et al. Acquisition of antibodies against Plasmodium falciparum merozoites and malaria immunity in young children and the influence of age, force of infection, and magnitude of response. Infect Immun. 2015;83:646–60.CrossRefPubMedPubMedCentral
8.
Richards JS, Arumugam TU, Reiling L, Healer J, Hodder AN, Fowkes FJ, et al. Identification and prioritization of merozoite antigens as targets of protective human immunity to Plasmodium falciparum malaria for vaccine and biomarker development. J Immunol. 2013;191:795–809.CrossRefPubMedPubMedCentral
9.
Fowkes FJ, Richards JS, Simpson JA, Beeson JG. The relationship between anti-merozoite antibodies and incidence of Plasmodium falciparum malaria: a systematic review and meta-analysis. PLoS Med. 2010;7:e1000218.CrossRefPubMedPubMedCentral
10.
Cutts JC, Powell R, Agius PA, Beeson JG, Simpson JA, Fowkes FJ. Immunological markers of Plasmodium vivax exposure and immunity: a systematic review and meta-analysis. BMC Med. 2014;12:150.CrossRefPubMedPubMedCentral
11.
Franca CT, Hostetler JB, Sharma S, White MT, Lin E, Kiniboro B, et al. An antibody screen of a Plasmodium vivax antigen library identifies novel merozoite proteins associated with clinical protection. PLoS Negl Trop Dis. 2016;10:e0004639.CrossRefPubMedPubMedCentral
12.
Gilson PR, Nebl T, Vukcevic D, Moritz RL, Sargeant T, Speed TP, et al. Identification and stoichiometry of glycosylphosphatidylinositol-anchored membrane proteins of the human malaria parasite Plasmodium falciparum. Mol Cell Proteom. 2006;5:1286–99.CrossRef
13.
Brattig NW, Kowalsky K, Liu X, Burchard GD, Kamena F, Seeberger PH. Plasmodium falciparum glycosylphosphatidylinositol toxin interacts with the membrane of non-parasitized red blood cells: a putative mechanism contributing to malaria anemia. Microbes Infect. 2008;10:885–91.CrossRefPubMed
14.
Schofield L, Grau GE. Immunological processes in malaria pathogenesis. Nat Rev Immunol. 2005;5:722–35.CrossRefPubMed
15.
Boutlis CS, Riley EM, Anstey NM, de Souza JB. Glycosylphosphatidylinositols in malaria pathogenesis and immunity: potential for therapeutic inhibition and vaccination. Curr Top Microbiol Immunol. 2005;297:145–85.PubMed
16.
Mbengue B, Niang B, Niang MS, Varela ML, Fall B, Fall MM, et al. Inflammatory cytokine and humoral responses to Plasmodium falciparum glycosylphosphatidylinositols correlates with malaria immunity and pathogenesis. Immun Inflamm Dis. 2016;4:24–34.CrossRefPubMed
17.
Swarts BM, Guo Z. Chemical synthesis of glycosylphosphatidylinositol anchors. Adv Carbohydr Chem Biochem. 2012;67:137–219.CrossRefPubMed
18.
Naik RS, Branch OH, Woods AS, Vijaykumar M, Perkins DJ, Nahlen BL, et al. Glycosylphosphatidylinositol anchors of Plasmodium falciparum: molecular characterization and naturally elicited antibody response that may provide immunity to malaria pathogenesis. J Exp Med. 2000;192:1563–76.CrossRefPubMedPubMedCentral
19.
Kamena F, Tamborrini M, Liu X, Kwon YU, Thompson F, Pluschke G, et al. Synthetic GPI array to study antitoxic malaria response. Nat Chem Biol. 2008;4:238–40.CrossRefPubMed
20.
Gerold P, Dieckmann-Schuppert A, Schwarz RT. Glycosylphosphatidylinositols synthesized by asexual erythrocytic stages of the malarial parasite, Plasmodium falciparum. Candidates for plasmodial glycosylphosphatidylinositol membrane anchor precursors and pathogenicity factors. J Biol Chem. 1994;269:2597–606.PubMed
21.
Tamborrini M, Liu X, Mugasa JP, Kwon YU, Kamena F, Seeberger PH, et al. Synthetic glycosylphosphatidylinositol microarray reveals differential antibody levels and fine specificities in children with mild and severe malaria. Bioorgan Med Chem. 2010;18:3747–52.CrossRef
22.
Arnott A, Mueller I, Ramsland PA, Siba PM, Reeder JC, Barry AE. Global population structure of the genes encoding the malaria vaccine candidate, Plasmodium vivax apical membrane antigen 1 (PvAMA1). PLoS Negl Trop Dis. 2013;7:e2506.CrossRefPubMedPubMedCentral
23.
Barry AE, Schultz L, Buckee CO, Reeder JC. Contrasting population structures of the genes encoding ten leading vaccine-candidate antigens of the human malaria parasite, Plasmodium falciparum. PLoS ONE. 2009;4:e8497.CrossRefPubMedPubMedCentral
24.
Tessema SK, Monk SL, Schultz MB, Tavul L, Reeder JC, Siba PM, et al. Phylogeography of var gene repertoires reveals fine-scale geospatial clustering of Plasmodium falciparum populations in a highly endemic area. Mol Ecol. 2015;24:484–97.CrossRefPubMed
25.
Barry AE, Trieu A, Fowkes FJ, Pablo J, Kalantari-Dehaghi M, Jasinskas A, et al. The stability and complexity of antibody responses to the major surface antigen of Plasmodium falciparum are associated with age in a malaria endemic area. Mol Cell Proteom. 2011;10(M111):008326.
26.
Gray JC, Corran PH, Mangia E, Gaunt MW, Li Q, Tetteh KK, et al. Profiling the antibody immune response against blood stage malaria vaccine candidates. Clin Chem. 2007;53:1244–53.CrossRefPubMed
27.
Cole-Tobian JL, Michon P, Biasor M, Richards JS, Beeson JG, Mueller I, et al. Strain-specific duffy binding protein antibodies correlate with protection against infection with homologous compared to heterologous Plasmodium vivax strains in Papua New Guinean children. Infect Immun. 2009;77:4009–17.CrossRefPubMedPubMedCentral
28.
Mueller I, Schoepflin S, Smith TA, Benton KL, Bretscher MT, Lin E, et al. Force of infection is key to understanding the epidemiology of Plasmodium falciparum malaria in Papua New Guinean children. Proc Natl Acad Sci USA. 2012;109:10030–5.CrossRefPubMedPubMedCentral
29.
Koepfli C, Colborn KL, Kiniboro B, Lin E, Speed TP, Siba PM, et al. A high force of Plasmodium vivax blood-stage infection drives the rapid acquisition of immunity in Papua New Guinean children. PLoS Negl Trop Dis. 2013;7:e2403.CrossRefPubMedPubMedCentral
30.
Lin E, Kiniboro B, Gray L, Dobbie S, Robinson L, Laumaea A, et al. Differential patterns of infection and disease with P. falciparum and P. vivax in young Papua New Guinean children. PLoS ONE. 2010;5:e9047.CrossRefPubMedPubMedCentral
31.
Schofield L, Hewitt MC, Evans K, Siomos MA, Seeberger PH. Synthetic GPI as a candidate anti-toxic vaccine in a model of malaria. Nature. 2002;418:785–9.CrossRefPubMed
32.
Boutlis CS, Gowda DC, Naik RS, Maguire GP, Mgone CS, Bockarie MJ, et al. Antibodies to Plasmodium falciparum glycosylphosphatidylinositols: inverse association with tolerance of parasitemia in Papua New Guinean children and adults. Infect Immun. 2002;70:505–57.CrossRef
33.
Hudson Keenihan SN, Ratiwayanto S, Soebianto S, Krisin Marwoto H, Krishnegowda G, et al. Age-dependent impairment of IgG responses to glycosylphosphatidylinositol with equal exposure to Plasmodium falciparum among Javanese migrants to Papua, Indonesia. Am J Trop Med Hyg. 2003;69:36–41.CrossRefPubMed
34.
de Souza JB, Todd J, Krishegowda G, Gowda DC, Kwiatkowski D, Riley EM. Prevalence and boosting of antibodies to Plasmodium falciparum glycosylphosphatidylinositols and evaluation of their association with protection from mild and severe clinical malaria. Infect Immun. 2002;70:5045–51.CrossRefPubMedPubMedCentral
35.
Lucas AH, Apicella MA, Taylor CE. Carbohydrate moieties as vaccine candidates. Clin Infect Dis. 2005;41:705–12.CrossRefPubMed
36.
Weiss GE, Traore B, Kayentao K, Ongoiba A, Doumbo S, Doumtabe D, et al. The Plasmodium falciparum-specific human memory B cell compartment expands gradually with repeated malaria infections. PLoS Pathog. 2010;6:e1000912.CrossRefPubMedPubMedCentral
37.
Jeurissen A, Ceuppens JL, Bossuyt X. T lymphocyte dependence of the antibody response to ‘T lymphocyte independent type 2’antigens. Immunology. 2004;111:1–7.CrossRefPubMedPubMedCentral
38.
Walker PS, Reid ME. The Gerbich blood group system: a review. Immunohematology. 2010;26:60–5.PubMed
39.
Salomao M, Zhang X, Yang Y, Lee S, Hartwig JH, Chasis JA, et al. Protein 4.1R-dependent multiprotein complex: new insights into the structural organization of the red blood cell membrane. Proc Natl Acad Sci USA. 2008;105:8026–31.CrossRefPubMedPubMedCentral
40.
41.
Wassmer SC, Carlton JM. Glycophorins, blood groups, and protection from severe malaria. Trends Parasitol. 2016;32:5–7.CrossRefPubMed
42.
Maier AG, Duraisingh MT, Reeder JC, Patel SS, Kazura JW, Zimmerman PA, et al. Plasmodium falciparum erythrocyte invasion through glycophorin C and selection for Gerbich negativity in human populations. Nat Med. 2003;9:87–92.CrossRefPubMed
43.
Serjeantson SW. A selective advantage for the Gerbich-negative phenotype in malarious areas of Papua New Guinea. P N G Med J. 1989;32:5–9.PubMed
44.
Lin E, Tavul L, Michon P, Richards JS, Dabod E, Beeson JG, et al. Minimal association of common red blood cell polymorphisms with Plasmodium falciparum infection and uncomplicated malaria in Papua New Guinean school children. Am J Trop Med Hyg. 2010;83:828–33.CrossRefPubMedPubMedCentral
45.
Patel SS, Mehlotra RK, Kastens W, Mgone CS, Kazura JW, Zimmerman PA. The association of the glycophorin C exon 3 deletion with ovalocytosis and malaria susceptibility in the Wosera, Papua New Guinea. Blood. 2001;98:3489–91.CrossRefPubMed
46.
Fowkes FJ, Michon P, Pilling L, Ripley RM, Tavul L, Imrie HJ, et al. Host erythrocyte polymorphisms and exposure to Plasmodium falciparum in Papua New Guinea. Malar J. 2008;7:1.CrossRefPubMedPubMedCentral
47.
Schofield L, Vivas L, Hackett F, Gerold P, Schwarz RT, Tachado S. Neutralizing monoclonal antibodies to glycosylphosphatidylinositol, the dominant TNF-alpha-inducing toxin of Plasmodium falciparum: prospects for the immunotherapy of severe malaria. Ann Trop Med Parasitol. 1993;87:617–26.CrossRefPubMed
48.
Schofield L, Novakovic S, Gerold P, Schwarz RT, McConville MJ, Tachado SD. Glycosylphosphatidylinositol toxin of Plasmodium up-regulates intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin expression in vascular endothelial cells and increases leukocyte and parasite cytoadherence via tyrosine kinase-dependent signal transduction. J Immunol. 1996;156:1886–96.PubMed
49.
Mbengue B, Diatta B, Niang B, Diagne N, Ndiaye M, Marrama L, et al. Differential kinetics of plasma procalcitonin levels in cerebral malaria in urban Senegalese patients according to disease outcome. Microb Res. 2011;2:80–4.CrossRef
50.
Boutlis CS, Fagan PK, Gowda DC, Lagog M, Mgone CS, Bockarie MJ, et al. Immunoglobulin G (IgG) responses to Plasmodium falciparum glycosylphosphatidylinositols are short-lived and predominantly of the IgG3 subclass. J Infect Dis. 2003;187:862–5.CrossRefPubMed
Metadata
Title
IgG antibodies to synthetic GPI are biomarkers of immune-status to both Plasmodium falciparum and Plasmodium vivax malaria in young children
Authors
Camila T. França
Connie S. N. Li Wai Suen
Amandine Carmagnac
Enmoore Lin
Benson Kiniboro
Peter Siba
Louis Schofield
Ivo Mueller
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2017
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/s12936-017-2042-2

Other articles of this Issue 1/2017

Malaria Journal 1/2017 Go to the issue

Research

Effect of climatic variability on malaria trends in Baringo County, Kenya

Research

Severe Plasmodium vivax infection in Korea

Research

Donor support for quality assurance and pharmacovigilance of anti-malarials in malaria-endemic countries

Research

A novel method for extracting nucleic acids from dried blood spots for ultrasensitive detection of low-density Plasmodium falciparum and Plasmodium vivax infections

Research

Relationships between infection with Plasmodium falciparum during pregnancy, measures of placental malaria, and adverse birth outcomes

Research

Comparative physical genome mapping of malaria vectors Anopheles sinensis and Anopheles gambiae
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Heart Failure Video

Year in Review: Heart failure and cardiomyopathies

Watch now

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits