• 1

    Miller LH, Baruch DI, Marsh K, Doumbo OK, 2002. The pathogenic basis of malaria. Nature 415 :673–679.

  • 2

    Beeson JG, Brown GV, 2002. Pathogenesis of Plasmodium falciparum malaria: the roles of parasite adhesion and antigenic variation. Cell Mol Life Sci 59 :258–271.

    • Search Google Scholar
    • Export Citation
  • 3

    Rogerson SJ, Chaiyaroj SC, Ng K, Reeder JC, Brown GV, 1995. Chondroitin sulfate A is a cell surface receptor for Plasmodium falciparum-infected erythrocytes. J Exp Med 182 :15–20.

    • Search Google Scholar
    • Export Citation
  • 4

    Fried M, Duffy PE, 1996. Adherence of Plasmodium falciparum to chondroitin sulfate A in the human placenta. Science 272 :1502–1504.

  • 5

    Beeson JG, Brown GV, Molyneux ME, Mhango C, Dzinjalamala F, Rogerson SJ, 1999. Plasmodium falciparum isolates from infected pregnant women and children are associated with distinct adhesive and antigenic properties. J Infect Dis 180 :464–472.

    • Search Google Scholar
    • Export Citation
  • 6

    Gysin J, Pouvelle B, Fievet N, Scherf A, Lepolard C, 1999. Ex vivo desequestration of Plasmodium falciparum-infected erythrocytes from human placenta by chondroitin sulfate A. Infect Immun 67 :6596–6602.

    • Search Google Scholar
    • Export Citation
  • 7

    Beeson JG, Rogerson SJ, Cooke BM, Reeder JC, Chai W, Lawson AM, Molyneux ME, Brown GV, 2000. Adhesion of Plasmodium falciparum-infected erythrocytes to hyaluronic acid in placental malaria. Nat Med 6 :86–90.

    • Search Google Scholar
    • Export Citation
  • 8

    Beeson JG, Brown GV, 2004. Plasmodium falciparum-infected erythrocytes demonstrate dual specificity for adhesion to hyaluronic acid and chondroitin sulfate A and have distinct adhesive properties. J Infect Dis 189 :169–179.

    • Search Google Scholar
    • Export Citation
  • 9

    Flick K, Scholander C, Chen Q, Fernandez V, Pouvelle B, Gysin J, Wahlgren M, 2001. Role of nonimmune IgG bound to PfEMP1 in placental malaria. Science 293 :2098–2100.

    • Search Google Scholar
    • Export Citation
  • 10

    Beeson JG, Reeder JC, Rogerson SJ, Brown GV, 2001. Parasite adhesion and immune evasion in placental malaria. Trends Parasitol 17 :331–337.

    • Search Google Scholar
    • Export Citation
  • 11

    Fried M, Nosten F, Brockman A, Brabin BJ, Duffy PE, 1998. Maternal antibodies block malaria. Nature 395 :851–852.

  • 12

    Maubert B, Fievet N, Tami G, Cot M, Boudin C, Deloron P, 1999. Development of antibodies against chondroitin sulfate A-adherent Plasmodium falciparum in pregnant women. Infect Immun 67 :5367–5371.

    • Search Google Scholar
    • Export Citation
  • 13

    Ricke CH, Staalsoe T, Koram K, Akanmori BD, Riley EM, Theander TG, Hviid L, 2000. Plasma antibodies from malaria-exposed pregnant women recognize variant surface antigens on Plasmodium falciparum-infected erythrocytes in a parity-dependent manner and block parasite adhesion to chondroitin sulfate A. J Immunol 165 :3309–3316.

    • Search Google Scholar
    • Export Citation
  • 14

    Staalsoe T, Megnekou R, Fievet N, Ricke CH, Zornig HD, Leke R, Taylor DW, Deloron P, Hviid L, 2001. Acquisition and decay of antibodies to pregnancy-associated variant antigens on the surface of Plasmodium falciparum-infected erythrocytes that protect against placental parasitemia. J Infect Dis 184 :618–626.

    • Search Google Scholar
    • Export Citation
  • 15

    Beeson JG, Mann EM, Elliott SR, Lema VM, Tadesse E, Molyneux ME, Brown GV, Rogerson SJ, 2004. Antibodies to variant surface antigens of Plasmodium falciparum-infected erythrocytes and adhesion inhibitory antibodies are associated with placental malaria and have overlapping and distinct targets. J Infect Dis 189 :540–551.

    • Search Google Scholar
    • Export Citation
  • 16

    Staalsoe T, Shulman CE, Bulmer JN, Kawuondo K, Marsh K, Hviid L, 2004. Variant surface antigen-specific IgG and protection against clinical consequences of pregnancy-associated Plasmodium falciparum malaria. Lancet 263 :283–289.

    • Search Google Scholar
    • Export Citation
  • 17

    Duffy PE, Fried M, 2003. Antibodies that inhibit Plasmodium falciparum adhesion to chondroitin sulfate A are associated with increased birth weight and the gestational age of newborns. Infect Immun 71 :6620–6623.

    • Search Google Scholar
    • Export Citation
  • 18

    Beeson JG, Mann EJ, Byrne TJ, Caragounis A, Elliott SR, Brown GV, Rogerson SJ, 2006. Antigenic differences and conservation among placental Plasmodium falciparum-infected erythrocytes and acquisition of variant-specific and cross-reactive antibodies. J Infect Dis 193 :721–730.

    • Search Google Scholar
    • Export Citation
  • 19

    Reeder JC, Cowman AF, Davern KM, Beeson JG, Thompson JK, Rogerson SJ, Brown GV, 1999. The adhesion of Plasmodium falciparum-infected erythrocytes to chondroitin sulfate A is mediated by PfEMP1. Proc Natl Acad Sci USA 96 :5198–5202.

    • Search Google Scholar
    • Export Citation
  • 20

    Buffet PA, Gamain B, Scheidig C, Baruch D, Smith JD, Hernandez-Rivas R, Pouvelle B, Oishi S, Fujii N, Fusai T, Parzy D, Miller LH, Gysin J, Scherf A, 1999. Plasmodium falciparum domain mediating adhesion to chondroitin sulfate A: a receptor for human placental infection. Proc Natl Acad Sci USA 96 :12743–12748.

    • Search Google Scholar
    • Export Citation
  • 21

    Gamain B, Trimnell AR, Scheidig C, Scherf A, Miller LH, Smith JD, 2005. Identification of multiple chondroitin sulfate A (CSA)-binding domains in the var2CSA gene transcribed in CSA-binding parasites. J Infect Dis 191 :1010–1013.

    • Search Google Scholar
    • Export Citation
  • 22

    Leech JH, Barnwell JW, Miller LH, Howard RJ, 1984. Identification of a strain-specific malarial antigen exposed on the surface of Plasmodium falciparum-infected erythrocytes. J Exp Med 159 :1567–1575.

    • Search Google Scholar
    • Export Citation
  • 23

    Biggs BA, Goozé L, Wycherley K, Wollish W, Southwell B, Leech JH, Brown GV, 1991. Antigenic variation in Plasmodium falciparum. Proc Natl Acad Sci USA 88 :9171–9174.

    • Search Google Scholar
    • Export Citation
  • 24

    Salanti A, Dahlbäck M, Turner L, Nielsen MA, Barfod L, Magistrado P, Jensen AT, Lavstsen T, Ofori MF, Marsh K, Hviid L, Theander TG, 2004. Evidence for the involvement of var2csa in pregnancy-associated malaria. J Exp Med 200 :1197–1203.

    • Search Google Scholar
    • Export Citation
  • 25

    Duffy MF, Byrne TJ, Elliott SR, Wilson DW, Rogerson SJ, Beeson JG, Noviyanti R, Brown GV, 2005. Broad analysis reveals a consistent pattern of var gene transcription in Plasmodium falciparum repeatedly selected for a defined adhesion phenotype. Mol Microbiol 56 :774–788.

    • Search Google Scholar
    • Export Citation
  • 26

    Viebig NK, Gamain B, Scheidig C, Lepolard C, Przyborski J, Lanzer M, Gysin J, Scherf A, 2005. A single member of the Plasmodium falciparum var multigene family determines cytoadhesion to the placental receptor chondroitin sulphate A. EMBO Rep 6 :775–781.

    • Search Google Scholar
    • Export Citation
  • 27

    Rowe JA, Kyes SA, 2004. The role of Plasmodium falciparum var genes in malaria in pregnancy. Mol Microbiol 53 :1011–1019.

  • 28

    Beeson JG, Rogerson SJ, Elliott SR, Duffy MF, 2005. Targets of protective antibodies to malaria during pregnancy. J Infect Dis 192 :1647–1650.

    • Search Google Scholar
    • Export Citation
  • 29

    Chaiyaroj SC, Angkasekwinai P, Buranakiti A, Looareesuwan S, Rogerson SJ, Brown GV, 1996. Cytoadherence characteristics of Plasmodium falciparum isolates from Thailand: evidence for chondroitin sulfate A as a cytoadherence receptor. Am J Trop Med Hyg 55 :76–80.

    • Search Google Scholar
    • Export Citation
  • 30

    Rogerson SJ, Tembenu R, Dobano C, Plitt S, Taylor TE, Molyneux ME, 1999. Cytoadherence characteristics of Plasmodium falciparum-infected erythrocytes from Malawian children with severe and uncomplicated malaria. Am J Trop Med Hyg 61 :467–472.

    • Search Google Scholar
    • Export Citation
  • 31

    Traore B, Muanza K, Looareesuwan S, Supavej S, Khusmith S, Danis M, Viriyavejakul P, Gay F, 2000. Cytoadherence characteristics of Plasmodium falciparum isolates in Thailand using an in vitro human lung endothelial cells model. Am J Trop Med Hyg 62 :38–44.

    • Search Google Scholar
    • Export Citation
  • 32

    Robert C, Pouvelle B, Meyer P, Muanza K, Fukioka H, Aikawa M, Scherf A, Gysin J, 1995. Chondroitin-4-sulphate (proteoglycan), a receptor for Plasmodium falciparum-infected erythrocyte adherence on brain microvascular endothelial cells. Res Immunol 146 :383–393.

    • Search Google Scholar
    • Export Citation
  • 33

    Mbogo CM, Mwangangi JM, Nzovu J, Gu W, Yan G, Gunter JT, Swalm C, Keating J, Regens JL, Shililu JI, Githure JI, Beier JC, 2003. Spatial and temporal heterogeneity of Anopheles mosquitoes and Plasmodium falciparum transmission along the Kenyan coast. Am J Trop Med Hyg 68 :734–742.

    • Search Google Scholar
    • Export Citation
  • 34

    Mwangi TW, Ross A, Snow RW, Marsh K, 2005. Case definitions of clinical malaria under different transmission conditions in Kilifi District, Kenya. J Infect Dis 191 :1932–1939.

    • Search Google Scholar
    • Export Citation
  • 35

    Cattani J, Tulloch J, Vrbova H, Jolley D, Gibson F, Moir J, Heywood P, Alpers M, Stevenson A, Clancy R, 1986. The epidemiology of malaria in a population surrounding Madang, Papua New Guinea. Am J Trop Med Hyg 36 :3–15.

    • Search Google Scholar
    • Export Citation
  • 36

    Beeson JG, Chai W, Rogerson SJ, Lawson AM, Brown GV, 1998. Inhibition of binding of malaria-infected erythrocytes by a tetradecasaccharide fraction from chondroitin sulfate A. Infect Immun 66 :3397–3402.

    • Search Google Scholar
    • Export Citation
  • 37

    Elliott S, Duffy MF, Byrne TJ, Beeson JG, Mann EJ, Wilson DW, Rogerson SJ, Brown GV, 2005. Cross-reactive surface epitopes on chondroitin sulfate A-adherent Plasmodium falciparum infected erythrocytes are associated with transcription of var2csa. Infect Immun 73 :2848–2856.

    • Search Google Scholar
    • Export Citation
  • 38

    Mount AM, Mwapasa V, Elliott SR, Beeson JG, Tadesse E, Lema VM, Molyneux ME, Meshnick SR, Rogerson SJ, 2004. Impairment of humoral immunity to Plasmodium falciparum malaria in pregnancy by HIV infection. Lancet 363 :1860–1867.

    • Search Google Scholar
    • Export Citation
  • 39

    Tuikue Ndam NG, Salanti A, Bertin G, Dahlback M, Fievet N, Turner L, Gaye A, Theander T, Deloron P, 2005. High level of var2csa transcription by Plasmodium falciparum isolated from the placenta. J Infect Dis 192 :331–335.

    • Search Google Scholar
    • Export Citation
  • 40

    Duffy MF, Caragounis A, Noviyanti R, Kyriacou HM, Choong EK, Boysen K, Healer J, Rowe JA, Molyneux ME, Brown GV, Rogerson SJ, 2006. Transcribed var genes associated with placental malaria in Malawian women. Infect Immun 74 :4875–4883.

    • Search Google Scholar
    • Export Citation
  • 41

    Kinyanjui SM, Bull P, Newbold CI, Marsh K, 2003. Kinetics of antibody responses to Plasmodium falciparum-infected erythrocyte variant surface antigens. J Infect Dis 187 :667–674.

    • Search Google Scholar
    • Export Citation
  • 42

    Duffy MF, Maier AG, Byrne TJ, Marty AJ, Elliott SR, O’Neill MT, Payne PD, Rogerson SJ, Cowman AF, Crabb BS, Brown GV, 2006. VAR2CSA is the principal ligand for chondroitin sulfate A in two allogeneic isolates of Plasmodium falciparum. Mol Biochem Parasitol 148 :117–124.

    • Search Google Scholar
    • Export Citation
  • 43

    Roberts DJ, Craig AG, Berendt AR, Pinches R, Nash G, Marsh G, Newbold CI, 1992. Rapid switching to multiple antigenic and adhesive phenotypes in malaria. Nature 357 :689–692.

    • Search Google Scholar
    • Export Citation
  • 44

    Fernandez V, Hommel M, Chen Q, Hagblom P, Wahlgren M, 1999. Small, clonally variant antigens expressed on the surface of Plasmodium falciparum-infected erythrocytes are encoded by the rif gene family and are targets of human immune responses. J Exp Med 190 :1393–1403.

    • Search Google Scholar
    • Export Citation
  • 45

    Kyes SA, Rowe JA, Kriek N, Newbold CI, 1999. Rifins: a second family of clonally variant proteins expressed on the surface of red cells infected with Plasmodium falciparum. Proc Natl Acad Sci USA 96 :9333–9338.

    • Search Google Scholar
    • Export Citation
  • 46

    Winter G, Kawai S, Haeggstrom M, Kaneko O, von Euler A, Kawazu S, Palm D, Fernandez V, Wahlgren M, 2005. SURFIN is a polymorphic antigen expressed on Plasmodium falciparum merozoites and infected erythrocytes. J Exp Med 201 :1853–1863.

    • Search Google Scholar
    • Export Citation
  • 47

    Voss TS, Healer J, Marty AJ, Duffy MF, Thompson JK, Beeson JG, Reeder JC, Crabb BS, Cowman AF, 2006. A var gene promoter controls allelic exclusion of virulence genes in Plasmodium falciparum malaria. Nature 439 :1004–1008.

    • Search Google Scholar
    • Export Citation
  • 48

    Trimnell AR, Kraemer SM, Mukherjee S, Phippard DJ, Janes JH, Flamoe E, Su XZ, Awadalla P, Smith JD, 2006. Global genetic diversity and evolution of var genes associated with placental and severe childhood malaria. Mol Biochem Parasitol 148 :169–180.

    • Search Google Scholar
    • Export Citation
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 

 

 

Antibodies among Men and Children to Placental-Binding Plasmodium falciparum-Infected Erythrocytes that Express var2csa

View More View Less
  • 1 Walter and Eliza Hall Institute of Medical Research, Victoria 3050, Australia; Centre for Geographic Medicine Research, Coast, Kenya Medical Research Institute, Kilifi, Kenya; Department of Medicine, University of Melbourne, Royal Melbourne Hospital, Victoria 3050, Australia; Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea
Restricted access

During pregnancy, specific variants of Plasmodium falciparum-infected erythrocytes (IEs) can accumulate in the placenta through adhesion to chondroitin sulfate A (CSA) mediated by expression of PfEMP1 encoded by var2csa-type genes. Antibodies against these variants are associated with protection from maternal malaria. We evaluated antibodies among Kenyan, Papua New Guinean, and Malawian men and Kenyan children against two different CSA-binding P. falciparum isolates expressing var2csa variants. Specific IgG was present at significant levels among some men and children from each population, suggesting exposure to these variants is not exclusive to pregnancy. However, the level and prevalence of antibodies was substantially lower overall than exposed multigravidas. IgG-binding was specific and did not represent antibodies to subpopulations of non-CSA-binding IEs, and some sera inhibited IE adhesion to CSA. These findings have significant implications for understanding malaria pathogenesis and immunity and may be significant for understanding the acquisition of immunity to maternal malaria.

Author Notes

Reprint requests: James Beeson, Walter and Eliza Hall Institute of Medical Research, Victoria 3050, Australia, Telephone: +61-3-9345-2555, Fax: +61-3-9347-0852, E-mail: beeson@wehi.edu.au.
Save