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Malaria Journal
Published in: Malaria Journal 1/2018

Open Access 01-12-2018 | Research

Assessment of the quality and quantity of naturally induced antibody responses to EBA175RIII–V in Ghanaian children living in two communities with varying malaria transmission patterns

Authors: Hamza B. Abagna, Festus K. Acquah, Ruth Okonu, Nii A. Aryee, Michael Theisen, Linda E. Amoah

Published in: Malaria Journal | Issue 1/2018

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Abstract

Background

Recent global reports on malaria suggest significant decrease in disease severity and an increase in control interventions in many malaria endemic countries, including Ghana. However, a major driving force sustaining malaria transmission in recent times is the asymptomatic carriage of malaria parasites, which can enhance immune responses against parasite antigens. This study determined the prevalence and relative avidities of naturally induced antibodies to EBA175RIII–VLl in asymptomatic children living in two communities with varying malaria transmission patterns.

Methods

An asexual stage Plasmodium falciparum antigen, EBA175RIII–VLl was expressed in Lactococcus lactis, purified and used in indirect ELISA to measure total and cytophilic IgG concentrations and avidities in children aged between 6 and 12 years. The children were selected from Obom and Abura, communities with perennial and seasonal malaria transmission, respectively. Venous blood samples were collected in July and October 2015 and again in January 2016. The multiplicity of infection and the genetic diversity of EBA175RIII circulating in both sites were also assessed using polymerase chain reaction.

Results

Asymptomatic parasite carriage in the children from Obom decreased from July (peak season), through October and January, however parasite carriage in children from Abura was bimodal, with the lowest prevalence estimated in October. Antibody concentrations over the course of the study remained stable within each study site however, children living in Obom had significantly higher EBA175RIII–VLl antibody concentrations than children living in Abura (P < 0.05, Mann–Whitney test). Over the course of the study, the relative antibody avidities of EBA175RIII–VLl IgG antibodies were similar within and between the sites.

Conclusion

Naturally acquired IgG concentrations but not relative antibody avidities to EBA175RIII–V were significantly higher in Obom where malaria transmission is perennial than in Abura, where malaria transmission is seasonal.
Appendix
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Literature
1.
WHO. World malaria report. Geneva: World Health Organization; 2016.
2.
3.
Kinyanjui SM, Bejon P, Osier FH, Bull PC, Marsh K. What you see is not what you get: implications of the brevity of antibody responses to malaria antigens and transmission heterogeneity in longitudinal studies of malaria immunity. Malar J. 2009;8:242.CrossRefPubMedPubMedCentral
4.
Bejon P, Warimwe G, Mackintosh CL, Mackinnon MJ, Kinyanjui SM, Musyoki JN, et al. Analysis of immunity to febrile malaria in children that distinguishes immunity from lack of exposure. Infect Immun. 2009;77:1917–23.CrossRefPubMedPubMedCentral
5.
Kinyanjui SM, Mwangi T, Bull PC, Newbold CI, Marsh K. Protection against clinical malaria by heterologous immunoglobulin G antibodies against malaria-infected erythrocyte variant surface antigens requires interaction with asymptomatic infections. J Infect Dis. 2004;190:1527–33.CrossRefPubMed
6.
Males S, Gaye O, Garcia A. Long-term asymptomatic carriage of Plasmodium falciparum protects from malaria attacks: a prospective study among Senegalese children. Clin Infect Dis. 2008;46:516–22.CrossRefPubMed
7.
Bottius E, Guanzirolli A, Trape JF, Rogier C, Konate L, Druilhe P. Malaria: even more chronic in nature than previously thought; evidence for subpatent parasitaemia detectable by the polymerase chain reaction. Trans R Soc Trop Med Hyg. 1996;90:15–9.CrossRefPubMed
8.
Laishram DD, Sutton PL, Nanda N, Sharma VL, Sobti RC, Carlton JM, et al. The complexities of malaria disease manifestations with a focus on asymptomatic malaria. Malar J. 2012;11:29.CrossRefPubMedPubMedCentral
9.
Porter MD, Nicki J, Pool CD, DeBot M, Illam RM, Brando C, et al. Transgenic parasites stably expressing full-length Plasmodium falciparum circumsporozoite protein as a model for vaccine down-selection in mice using sterile protection as an endpoint. Clin Vaccine Immunol. 2013;20:803–10.CrossRefPubMedPubMedCentral
10.
McCarra MB, Ayodo G, Sumba PO, Kazura JW, Moormann AM, Narum DL, et al. Antibodies to Plasmodium falciparum erythrocyte-binding antigen-175 are associated with protection from clinical malaria. Pediatr Infect Dis J. 2011;30:1037–42.CrossRefPubMedPubMedCentral
11.
Okenu DM, Riley EM, Bickle QD, Agomo PU, Barbosa A, Daugherty JR, et al. Analysis of human antibodies to erythrocyte binding antigen 175 of Plasmodium falciparum. Infect Immun. 2000;68:5559–66.CrossRefPubMedPubMedCentral
12.
Chen E, Paing MM, Salinas N, Sim BK, Tolia NH. Structural and functional basis for inhibition of erythrocyte invasion by antibodies that target Plasmodium falciparum EBA-175. PLoS Pathog. 2013;9:e1003390.CrossRefPubMedPubMedCentral
13.
Sim B. EBA-175: an erythrocyte-binding ligand of Plasmodium falciparum. Parasitol Today. 1995;11:213–7.CrossRefPubMed
14.
Badiane AS, Bei AK, Ahouidi AD, Patel SD, Salinas N, Ndiaye D, et al. Inhibitory humoral responses to the Plasmodium falciparum vaccine candidate EBA-175 are independent of the erythrocyte invasion pathway. Clin Vaccine Immunol. 2013;20:1238–45.CrossRefPubMedPubMedCentral
15.
Liang H, Narum DL, Fuhrmann SR, Luu T, Sim BK. A recombinant baculovirus-expressed Plasmodium falciparum receptor-binding domain of erythrocyte binding protein EBA-175 biologically mimics native protein. Infect Immun. 2000;68:3564–8.CrossRefPubMedPubMedCentral
16.
Jiang L, Gaur D, Mu J, Zhou H, Long CA, Miller LH. Evidence for erythrocyte-binding antigen 175 as a component of a ligand-blocking blood-stage malaria vaccine. Proc Natl Acad Sci USA. 2011;108:7553–8.CrossRefPubMedPubMedCentral
17.
Richards JS, Stanisic DI, Fowkes FJ, Tavul L, Dabod E, Thompson JK, et al. Association between naturally acquired antibodies to erythrocyte-binding antigens of Plasmodium falciparum and protection from malaria and high-density parasitemia. Clin Infect Dis. 2010;51:e50–60.CrossRefPubMed
18.
Sim BK, Narum DL, Liang H, Fuhrmann SR, Obaldia N 3rd, Gramzinski R, et al. Induction of biologically active antibodies in mice, rabbits, and monkeys by Plasmodium falciparum EBA-175 region II DNA vaccine. Mol Med. 2001;7:247–54.PubMedPubMedCentral
19.
Irani V, Ramsland PA, Guy AJ, Siba PM, Mueller I, Richards JS, et al. Acquisition of functional antibodies that block the binding of Erythrocyte-Binding Antigen 175 and protection against Plasmodium falciparum malaria in children. Clin Infect Dis. 2015;61:1244–52.CrossRefPubMedPubMedCentral
20.
Lopaticki S, Maier AG, Thompson J, Wilson DW, Tham WH, Triglia T, et al. Reticulocyte and erythrocyte binding-like proteins function cooperatively in invasion of human erythrocytes by malaria parasites. Infect Immun. 2011;79:1107–17.CrossRefPubMed
21.
Reed MB, Caruana SR, Batchelor AH, Thompson JK, Crabb BS, Cowman AF. Targeted disruption of an erythrocyte binding antigen in Plasmodium falciparum is associated with a switch toward a sialic acid-independent pathway of invasion. Proc Natl Acad Sci USA. 2000;97:7509–14.CrossRefPubMedPubMedCentral
22.
Toure FS, Bisseye C, Mavoungou E. Imbalanced distribution of Plasmodium falciparum EBA-175 genotypes related to clinical status in children from Bakoumba, Gabon. Clin Med Res. 2006;4:7–11.CrossRefPubMedPubMedCentral
23.
Healer J, Thompson JK, Riglar DT, Wilson DW, Chiu YH, Miura K, et al. Vaccination with conserved regions of erythrocyte-binding antigens induces neutralizing antibodies against multiple strains of Plasmodium falciparum. PLoS ONE. 2013;8:e72504.CrossRefPubMedPubMedCentral
24.
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
25.
Chiu CY, White MT, Healer J, Thompson JK, Siba PM, Mueller I, et al. Different regions of Plasmodium falciparum Erythrocyte-Binding Antigen 175 induce antibody responses to infection of varied efficacy. J Infect Dis. 2016;214:96–104.CrossRefPubMed
26.
Ibison F, Olotu A, Muema DM, Mwacharo J, Ohuma E, Kimani D, et al. Lack of avidity maturation of merozoite antigen-specific antibodies with increasing exposure to Plasmodium falciparum amongst children and adults exposed to endemic malaria in Kenya. PLoS ONE. 2012;7:e52939.CrossRefPubMedPubMedCentral
27.
Akpogheneta OJ, Dunyo S, Pinder M, Conway DJ. Boosting antibody responses to Plasmodium falciparum merozoite antigens in children with highly seasonal exposure to infection. Parasite Immunol. 2010;32:296–304.CrossRefPubMedPubMedCentral
28.
Amoah LE, Opong A, Ayanful-Torgby R, Abankwa J, Acquah FK. Prevalence of G6PD deficiency and Plasmodium falciparum parasites in asymptomatic school children living in southern Ghana. Malar J. 2016;15:388.CrossRefPubMedPubMedCentral
29.
WHO. Giemsa staining of malaria blood films. In: Malaria microscopy standard operating procedure. MM-SOP-07A2016. Geneva: World Health Organization; 2016.
30.
WHO. Malaria parasite counting. In: Malaria microscopy standard operating procedure. MM-SOP-09. Geneva: World Health Organization; 2016.
31.
Baidjoe A, Stone W, Ploemen I, Shagari S, Grignard L, Osoti V, et al. Combined DNA extraction and antibody elution from filter papers for the assessment of malaria transmission intensity in epidemiological studies. Malar J. 2013;12:272.CrossRefPubMedPubMedCentral
32.
Singh B, Bobogare A, Cox-Singh J, Snounou G, Abdullah MS, Rahman HA. A genus- and species-specific nested polymerase chain reaction malaria detection assay for epidemiologic studies. Am J Trop Med Hyg. 1999;60:687–92.CrossRefPubMed
33.
Ayanful-Torgby R, Oppong A, Abankwa J, Acquah F, Williamson KC, Amoah LE. Plasmodium falciparum genotype and gametocyte prevalence in children with uncomplicated malaria in coastal Ghana. Malar J. 2016;15:592.CrossRefPubMedPubMedCentral
34.
Acquah FK, Obboh EK, Asare K, Boampong JN, Nuvor SV, Singh SK, et al. Antibody responses to two new Lactococcus lactis-produced recombinant Pfs48/45 and Pfs230 proteins increase with age in malaria patients living in the Central Region of Ghana. Malar J. 2017;16:306.CrossRefPubMedPubMedCentral
35.
Theisen M, Roeffen W, Singh SK, Andersen G, Amoah L, van de Vegte-Bolmer M, et al. A multi-stage malaria vaccine candidate targeting both transmission and asexual parasite life-cycle stages. Vaccine. 2014;32:2623–30.CrossRefPubMed
36.
Singh SK, Roeffen W, Andersen G, Bousema T, Christiansen M, Sauerwein R, et al. A Plasmodium falciparum 48/45 single epitope R0.6C subunit protein elicits high levels of transmission blocking antibodies. Vaccine. 2015;33:1981–6.CrossRefPubMed
37.
38.
Gasteiger E, Hoogland C, Gattiker A, Duvaud S, Wilkins MR, Appel RD, et al. Protein identification and analysis tool on the ExPASy server. In: Walker JM, editor. The proteomics protocols handbook. New York: Humana Press; 2005. p. 571–607.CrossRef
39.
Bates D, Maechler M, Bolker B, Walker S. Fitting linear mixed-effects models using {lme4}. J Stat Softw. 2015;67:1–48.CrossRef
40.
Jones TR, Narum DL, Gozalo AS, Aguiar J, Fuhrmann SR, Liang H, et al. Protection of Aotus monkeys by Plasmodium falciparum EBA-175 region II DNA prime-protein boost immunization regimen. J Infect Dis. 2001;183:303–12.CrossRefPubMed
41.
Liang H, Sim BK. Conservation of structure and function of the erythrocyte-binding domain of Plasmodium falciparum EBA-175. Mol Biochem Parasitol. 1997;84:241–5.CrossRefPubMed
42.
Ozwara H, Kocken CH, Conway DJ, Mwenda JM, Thomas AW. Comparative analysis of Plasmodium reichenowi and P. falciparum erythrocyte-binding proteins reveals selection to maintain polymorphism in the erythrocyte-binding region of EBA-175. Mol Biochem Parasitol. 2001;116:81–4.CrossRefPubMed
43.
Baum J, Thomas AW, Conway DJ. Evidence for diversifying selection on erythrocyte-binding antigens of Plasmodium falciparum and P. vivax. Genetics. 2003;163:1327–36.PubMedPubMedCentral
44.
Noland GS, Hendel-Paterson B, Min XM, Moormann AM, Vulule JM, Narum DL, et al. Low prevalence of antibodies to preerythrocytic but not blood-stage Plasmodium falciparum antigens in an area of unstable malaria transmission compared to prevalence in an area of stable malaria transmission. Infect Immun. 2008;76:5721–8.CrossRefPubMedPubMedCentral
45.
Osier FH, Fegan G, Polley SD, Murungi L, Verra F, Tetteh KK, et al. Breadth and magnitude of antibody responses to multiple Plasmodium falciparum merozoite antigens are associated with protection from clinical malaria. Infect Immun. 2008;76:2240–8.CrossRefPubMedPubMedCentral
46.
Toure FS, Deloron P, Migot-Nabias F. Analysis of human antibodies to erythrocyte binding antigen 175 peptide 4 of Plasmodium falciparum. Clin Med Res. 2006;4:1–6.CrossRefPubMedPubMedCentral
47.
Shirai A, Matsuyama A, Yashiroda Y, Hashimoto A, Kawamura Y, Arai R, et al. Global analysis of gel mobility of proteins and its use in target identification. J Biol Chem. 2008;283:10745–52.CrossRefPubMed
48.
Theisen M, Vuust J, Gottschau A, Jepsen S, Hogh B. Antigenicity and immunogenicity of recombinant glutamate-rich protein of Plasmodium falciparum expressed in Escherichia coli. Clin Diagn Lab Immunol. 1995;2:30–4.PubMedPubMedCentral
49.
Theisen M, Soe S, Brunstedt K, Follmann F, Bredmose L, Israelsen H, et al. A Plasmodium falciparum GLURP-MSP3 chimeric protein; expression in Lactococcus lactis, immunogenicity and induction of biologically active antibodies. Vaccine. 2004;22:1188–98.CrossRefPubMed
50.
Owusu EDA, Brown CA, Grobusch MP, Mens P. Prevalence of Plasmodium falciparum and non-P. falciparum infections in a highland district in Ghana, and the influence of HIV and sickle cell disease. Malar J. 2017;16:167.CrossRefPubMedPubMedCentral
51.
Soulama I, Bougouma EC, Diarra A, Nebie I, Sirima SB. Low-high season variation in Plasmodium falciparum erythrocyte binding antigen 175 (eba-175) allelic forms in malaria endemic area of Burkina Faso. Trop Med Int Health. 2010;15:51–9.PubMed
52.
Perce-da-Silva DS, Banic DM, Lima-Junior JC, Santos F, Daniel-Ribeiro CT, de Oliveira-Ferreira J, et al. Evaluation of allelic forms of the erythrocyte binding antigen 175 (EBA-175) in Plasmodium falciparum field isolates from Brazilian endemic area. Malar J. 2011;10:146.CrossRefPubMedPubMedCentral
53.
Cramer JP, Mockenhaupt FP, Mohl I, Dittrich S, Dietz E, Otchwemah RN, et al. Allelic dimorphism of the erythrocyte binding antigen-175 (eba-175) gene of Plasmodium falciparum and severe malaria: significant association of the C-segment with fatal outcome in Ghanaian children. Malar J. 2004;3:11.CrossRefPubMedPubMedCentral
54.
Stewart L, Gosling R, Griffin J, Gesase S, Campo J, Hashim R, et al. Rapid assessment of malaria transmission using age-specific sero-conversion rates. PLoS ONE. 2009;4:e6083.CrossRefPubMedPubMedCentral
55.
Bousema T, Youssef RM, Cook J, Cox J, Alegana VA, Amran J, et al. Serologic markers for detecting malaria in areas of low endemicity, Somalia, 2008. Emerg Infect Dis. 2010;16:392–9.CrossRefPubMedPubMedCentral
56.
Tongren JE, Drakeley CJ, McDonald SL, Reyburn HG, Manjurano A, Nkya WM, et al. Target antigen, age, and duration of antigen exposure independently regulate immunoglobulin G subclass switching in malaria. Infect Immun. 2006;74:257–64.CrossRefPubMedPubMedCentral
57.
Supargiyono S, Bretscher MT, Wijayanti MA, Sutanto I, Nugraheni D, Rozqie R, et al. Seasonal changes in the antibody responses against Plasmodium falciparum merozoite surface antigens in areas of differing malaria endemicity in Indonesia. Malar J. 2013;12:444.CrossRefPubMedPubMedCentral
58.
Ahmed Ismail H, Tijani MK, Langer C, Reiling L, White MT, Beeson JG, et al. Subclass responses and their half-lives for antibodies against EBA175 and PfRh2 in naturally acquired immunity against Plasmodium falciparum malaria. Malar J. 2014;13:425.CrossRefPubMedPubMedCentral
59.
Weaver R, Reiling L, Feng G, Drew DR, Mueller I, Siba PM, et al. The association between naturally acquired IgG subclass specific antibodies to the PfRH5 invasion complex and protection from Plasmodium falciparum malaria. Sci Rep. 2016;6:33094.CrossRefPubMedPubMedCentral
60.
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
61.
Ssewanyana I, Arinaitwe E, Nankabirwa JI, Yeka A, Sullivan R, Kamya MR, et al. Avidity of anti-malarial antibodies inversely related to transmission intensity at three sites in Uganda. Malar J. 2017;16:67.CrossRefPubMedPubMedCentral
62.
Perciani CT, Peixoto PS, Dias WO, Kubrusly FS, Tanizaki MM. Improved method to calculate the antibody avidity index. J Clin Lab Anal. 2007;21:201–6.CrossRefPubMed
63.
Tutterrow YL, Salanti A, Avril M, Smith JD, Pagano IS, Ako S, et al. High avidity antibodies to full-length VAR2CSA correlate with absence of placental malaria. PLoS ONE. 2012;7:e40049.CrossRefPubMedPubMedCentral
64.
Cadman ET, Abdallah AY, Voisine C, Sponaas AM, Corran P, Lamb T, et al. Alterations of splenic architecture in malaria are induced independently of toll-like receptors 2, 4, and 9 or MyD88 and may affect antibody affinity. Infect Immun. 2008;76:3924–31.CrossRefPubMedPubMedCentral
Metadata
Title
Assessment of the quality and quantity of naturally induced antibody responses to EBA175RIII–V in Ghanaian children living in two communities with varying malaria transmission patterns
Authors
Hamza B. Abagna
Festus K. Acquah
Ruth Okonu
Nii A. Aryee
Michael Theisen
Linda E. Amoah
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2018
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/s12936-017-2167-3

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