ANTIBODY REACTIVITY TO LINEAR EPITOPES OF PLASMODIUM FALCIPARUM CYTOADHERENCE-LINKED ASEXUAL GENE 9 IN ASYMPTOMATIC CHILDREN AND ADULTS FROM PAPUA NEW GUINEA

KATHARINE R. TRENHOLME Division of Infectious Diseases and Immunology, The Australian Centre for International and Tropical Health and Nutrition, The Queensland Institute of Medical Research, Brisbane, Queensland, Australia; International Health Program, Menzies School of Health Research, Casuarina, Darwin, Northern Territory, Australia; Papua New Guinea Institute of Medical Research, Madang, Papua, New Guinea

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CRAIG S. BOUTLIS Division of Infectious Diseases and Immunology, The Australian Centre for International and Tropical Health and Nutrition, The Queensland Institute of Medical Research, Brisbane, Queensland, Australia; International Health Program, Menzies School of Health Research, Casuarina, Darwin, Northern Territory, Australia; Papua New Guinea Institute of Medical Research, Madang, Papua, New Guinea

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RACHEL KUNS Division of Infectious Diseases and Immunology, The Australian Centre for International and Tropical Health and Nutrition, The Queensland Institute of Medical Research, Brisbane, Queensland, Australia; International Health Program, Menzies School of Health Research, Casuarina, Darwin, Northern Territory, Australia; Papua New Guinea Institute of Medical Research, Madang, Papua, New Guinea

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MOSES LAGOG Division of Infectious Diseases and Immunology, The Australian Centre for International and Tropical Health and Nutrition, The Queensland Institute of Medical Research, Brisbane, Queensland, Australia; International Health Program, Menzies School of Health Research, Casuarina, Darwin, Northern Territory, Australia; Papua New Guinea Institute of Medical Research, Madang, Papua, New Guinea

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MOSES J. BOCKARIE Division of Infectious Diseases and Immunology, The Australian Centre for International and Tropical Health and Nutrition, The Queensland Institute of Medical Research, Brisbane, Queensland, Australia; International Health Program, Menzies School of Health Research, Casuarina, Darwin, Northern Territory, Australia; Papua New Guinea Institute of Medical Research, Madang, Papua, New Guinea

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MICHELLE L. GATTON Division of Infectious Diseases and Immunology, The Australian Centre for International and Tropical Health and Nutrition, The Queensland Institute of Medical Research, Brisbane, Queensland, Australia; International Health Program, Menzies School of Health Research, Casuarina, Darwin, Northern Territory, Australia; Papua New Guinea Institute of Medical Research, Madang, Papua, New Guinea

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DAVID J. KEMP Division of Infectious Diseases and Immunology, The Australian Centre for International and Tropical Health and Nutrition, The Queensland Institute of Medical Research, Brisbane, Queensland, Australia; International Health Program, Menzies School of Health Research, Casuarina, Darwin, Northern Territory, Australia; Papua New Guinea Institute of Medical Research, Madang, Papua, New Guinea

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MICHAEL F. GOOD Division of Infectious Diseases and Immunology, The Australian Centre for International and Tropical Health and Nutrition, The Queensland Institute of Medical Research, Brisbane, Queensland, Australia; International Health Program, Menzies School of Health Research, Casuarina, Darwin, Northern Territory, Australia; Papua New Guinea Institute of Medical Research, Madang, Papua, New Guinea

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NICHOLAS M. ANSTEY Division of Infectious Diseases and Immunology, The Australian Centre for International and Tropical Health and Nutrition, The Queensland Institute of Medical Research, Brisbane, Queensland, Australia; International Health Program, Menzies School of Health Research, Casuarina, Darwin, Northern Territory, Australia; Papua New Guinea Institute of Medical Research, Madang, Papua, New Guinea

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DONALD L. GARDINER Division of Infectious Diseases and Immunology, The Australian Centre for International and Tropical Health and Nutrition, The Queensland Institute of Medical Research, Brisbane, Queensland, Australia; International Health Program, Menzies School of Health Research, Casuarina, Darwin, Northern Territory, Australia; Papua New Guinea Institute of Medical Research, Madang, Papua, New Guinea

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The cytoadherence-linked asexual gene 9 (clag 9) of Plasmodium falciparum has been implicated in the cytoadherence of infected erythrocytes. To determine the immunogenicity of the clag 9 gene product (CLAG 9 protein) in humans, we measured antibody responses to 11 synthetic CLAG 9 peptides in a group of 177 asymptomatic children and adults subject to intense malaria exposure in Madang, Papua New Guinea. The CLAG 9 peptides were immunogenic in adults and children. Antibody responses to peptides 4 and 10 were high across all age groups and detectable in a majority of children less than five years of age. While CLAG 9 peptides are immunogenic in humans, longitudinal studies will be required to determine the longevity of antibody responses to CLAG 9 and their role in protection from disease.

Author Notes

Reprint requests: Katharine R. Trenholme, Queensland Institute of Medical Research, 300 Herston Road, Queensland, Australia, 4006, E-mail: kathT@qimr.edu.au.
  • 1

    Miller LH, Good MF, Milon G, 1994. Malaria pathogenesis. Science 264 :1878–1883.

  • 2

    Cohen S, McGregor IA, Carrington S, 1961. Gamma-globulin and acquired immunity to human malaria. Nauchni Tr Vissh Med Inst Sofiia 192 :733–737.

    • Search Google Scholar
    • Export Citation
  • 3

    Cohen S, Butcher GA, 1970. Properties of protective malarial antibody. Nature 225 :732–734.

  • 4

    Sabchareon A, Burnouf T, Ouattara D, Attanath P, Bouharoun-Tayoun H, Chantavanich P, Foucault C, Chongsuphajaisiddhi T, Druilhe P, 1991. Parasitologic and clinical human response to immunoglobulin administration in falciparum malaria. Am J Trop Med Hyg 45 :297–308.

    • Search Google Scholar
    • Export Citation
  • 5

    Collins WE, Pye D, Crewther PE, Vandenberg KL, Galland GG, Sulzer AJ, Kemp DJ, Edwards SJ, Coppel RL, Sullivan JS, 1994. Protective immunity induced in squirrel monkeys with recombinant apical membrane antigen-1 of Plasmodium fragile. Am J Trop Med Hyg 51 :711–719.

    • Search Google Scholar
    • Export Citation
  • 6

    Inselburg J, Bzik DJ, Li WB, Green KM, Kansopon J, Hahm BK, Bathurst IC, Barr PJ, Rossan RN, 1991. Protective immunity induced in Aotus monkeys by recombinant SERA proteins of Plasmodium falciparum. Infect Immun 59 :1247–1250.

    • Search Google Scholar
    • Export Citation
  • 7

    Baruch DI, Pasloske BL, Singh HB, Bi X, Ma XC, Feldman M, Taraschi TF, Howard RJ, 1995. Cloning the P. falciparum gene encoding PfEMP1, a malarial variant antigen and adherence receptor on the surface of parasitized human erythrocytes. Cell 82 :77–87.

    • Search Google Scholar
    • Export Citation
  • 8

    Fernandez V, Hommel M, Chen Q, Hagblom P, Wahlgren M, 1999. Small, clonally variant antigens expressed on the surface of the Plasmodium falciparum-infected erythrocyte are encoded by the rif gene family and are the target of human immune responses. J Exp Med 190 :1393–1404.

    • Search Google Scholar
    • Export Citation
  • 9

    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 U S A 96 :9333–9338.

    • Search Google Scholar
    • Export Citation
  • 10

    Ockenhouse CF, Klotz FW, Tandon NN, Jamieson GA, 1991. Sequestrin, a CD36 recognition protein on Plasmodium falciparum malaria-infected erythrocytes identified by anti-idio-type antibodies. Proc Natl Acad Sci U S A 88 :3175–3179.

    • Search Google Scholar
    • Export Citation
  • 11

    Pouvelle B, Buffet PA, Lepolard C, Scherf A, Gysin J, 2000. Cytoadhesion of Plasmodium falciparum ring-stage-infected erythrocytes. Nat Med 6 :1264–1268.

    • Search Google Scholar
    • Export Citation
  • 12

    Smith JD, Chitnis CE, Craig AG, Roberts DJ, Hudson-Taylor DE, Peterson DS, Pinches R, Newbold CI, Miller LH, 1995. Switches in expression of Plasmodium falciparum var genes correlate with changes in antigenic and cytoadherent phenotypes of infected erythrocytes. Cell 82 :101–110.

    • Search Google Scholar
    • Export Citation
  • 13

    Su XZ, Heatwole VM, Wertheimer SP, Guinet F, Herrfeldt JA, Peterson DS, Ravetch JA, Wellems TE, 1995. The large diverse gene family var encodes proteins involved in cytoadherence and antigenic variation of Plasmodium falciparum-infected erythrocytes. Cell 82 :89–100.

    • Search Google Scholar
    • Export Citation
  • 14

    Dodoo D, Staalsoe T, Giha H, Kurtzhals JA, Akanmori BD, Koram K, Dunyo S, Nkrumah FK, Hviid L, Theander TG, 2001. Antibodies to variant antigens on the surfaces of infected erythrocytes are associated with protection from malaria in Ghanaian children. Infect Immun 69 :3713–3718.

    • Search Google Scholar
    • Export Citation
  • 15

    Bull PC, Marsh K, 2002. The role of antibodies to Plasmodium falciparum-infected-erythrocyte surface antigens in naturally acquired immunity to malaria. Trends Microbiol 10 :55–58.

    • Search Google Scholar
    • Export Citation
  • 16

    Marsh K, Otoo L, Hayes RJ, Carson DC, Greenwood BM, 1989. Antibodies to blood stage antigens of Plasmodium falciparum in rural Gambians and their relation to protection against infection. Trans R Soc Trop Med Hyg 83 :293–303.

    • Search Google Scholar
    • Export Citation
  • 17

    Smith JD, Craig AG, Kriek N, Hudson-Taylor D, Kyes S, Fagen T, Pinches R, Baruch DI, Newbold CI, Miller LH, 2000. Identification of a Plasmodium falciparum intercellular adhesion molecule-1 binding domain: a parasite adhesion trait implicated in cerebral malaria. Proc Natl Acad Sci U S A 97 :1766–1771.

    • Search Google Scholar
    • Export Citation
  • 18

    Gardiner DL, Holt DC, Thomas EA, Kemp DJ, Trenholme KR, 2000. Inhibition of Plasmodium falciparum clag9 gene function by antisense RNA. Mol Biochem Parasitol 110 :33–41.

    • Search Google Scholar
    • Export Citation
  • 19

    Trenholme KR, Gardiner DL, Holt DC, Thomas EA, Cowman AF, Kemp DJ, 2000. clag9: A cytoadherence gene in Plasmodium falciparum essential for binding of parasitized erythrocytes to CD36. Proc Natl Acad Sci U S A 97 :4029–4033.

    • Search Google Scholar
    • Export Citation
  • 20

    Kaneko O, Tsuboi T, Ling IT, Howell S, Shirano M, Tachibana M, Cao YM, Holder AA, Torii M, 2001. The high molecular mass rhoptry protein, RhopH1, is encoded by members of the clag multigene family in Plasmodium falciparum and Plasmodium yoelii. Mol Biochem Parasitol 118 :223–231.

    • Search Google Scholar
    • Export Citation
  • 21

    Manski-Nankervis JA, Gardiner DL, Hawthorne P, Holt DC, Edwards M, Kemp DJ, Trenholme KR, 2000. The sequence of clag 9, a subtelomeric gene of Plasmodium falciparum is highly conserved. Mol Biochem Parasitol 111 :437–440.

    • Search Google Scholar
    • Export Citation
  • 22

    Gardiner DL, Spielmann T, Dixon MW, Hawthorne PL, Ortega MR, Anderson KL, Skinner-Adams TS, Kemp DJ, Trenholme KR, 2004. CLAG 9 is located in the rhoptries of Plasmodium falciparum. Parasitol Res 93 :64–67.

    • Search Google Scholar
    • Export Citation
  • 23

    Sam-Yellowe TY, Shio H, Perkins ME, 1988. Secretion of Plasmodium falciparum rhoptry protein into the plasma membrane of host erythrocytes. J Cell Biol 106 :1507–1513.

    • Search Google Scholar
    • Export Citation
  • 24

    Douki JB, Sterkers Y, Lepolard C, Traore B, Costa FT, Scherf A, Gysin J, 2003. Adhesion of normal and Plasmodium falciparum ring-infected erythrocytes to endothelial cells and the placenta involves the rhoptry-derived ring surface protein-2. Blood 101 :5025–5032.

    • Search Google Scholar
    • Export Citation
  • 25

    Kriek N, Tilley L, Horrocks P, Pinches R, Elford BC, Ferguson DJ, Lingelbach K, Newbold CI, 2003. Characterization of the pathway for transport of the cytoadherence-mediating protein, PfEMP1, to the host cell surface in malaria parasite-infected erythrocytes. Mol Microbiol 50 :1215–1227.

    • Search Google Scholar
    • Export Citation
  • 26

    Boutlis CS, Gowda DC, Naik RS, Maguire GP, Mgone CS, Bockarie MJ, Lagog M, Ibam E, Lorry K, Anstey NM, 2002. Antibodies to Plasmodium falciparum glycosylphosphatidylinositols: inverse association with tolerance of parasitemia in Papua New Guinean children and adults. Infect Immun 70 :5052–5057.

    • Search Google Scholar
    • Export Citation
  • 27

    Cattani JA, Tulloch JL, Vrbova H, Jolley D, Gibson FD, Moir JS, Heywood PF, Alpers MP, Stevenson A, Clancy R, 1986. The epidemiology of malaria in a population surrounding Madang, Papua New Guinea. Am J Trop Med Hyg 35 :3–15.

    • Search Google Scholar
    • Export Citation
  • 28

    Cox MJ, Kum DE, Tavul L, Narara A, Raiko A, Baisor M, Alpers MP, Medley GF, Day KP, 1994. Dynamics of malaria parasitaemia associated with febrile illness in children from a rural area of Madang, Papua New Guinea. Trans R Soc Trop Med Hyg 88 :191–197.

    • Search Google Scholar
    • Export Citation
  • 29

    Burkot TR, Graves PM, Cattan JA, Wirtz RA, Gibson FD, 1987. The efficiency of sporozoite transmission in the human malarias, Plasmodium falciparum and P. vivax. Bull World Health Organ 65 :375–380.

    • Search Google Scholar
    • Export Citation
  • 30

    Bruce MC, Donnelly CA, Packer M, Lagog M, Gibson N, Narara A, Walliker D, Alpers MP, Day KP, 2000. Age- and species-specific duration of infection in asymptomatic malaria infections in Papua New Guinea. Parasitology 121 :247–256.

    • Search Google Scholar
    • Export Citation
  • 31

    Delley V, Bouvier P, Breslow N, Doumbo O, Sagara I, Diakite M, Mauris A, Dolo A, Rougemont A, 2000. What does a single determination of malaria parasite density mean? A longitudinal survey in Mali. Trop Med Int Health 5 :404–412.

    • Search Google Scholar
    • Export Citation
  • 32

    Schmidt R, Steinhilber W, Ruppert C, Daum C, Grimminger F, Seeger W, Gunther A, 2002. An ELISA technique for quantification of surfactant apoprotein (SP)-C in bronchoalveolar lavage fluid. Am J Respir Crit Care Med 165 :470–474.

    • Search Google Scholar
    • Export Citation
  • 33

    Box GEP, Cox DR, 1964. An analysis of transformations (with discussion). J R Stat Soc 26 :211–252.

  • 34

    al Yaman F, Genton B, Kramer KJ, Chang SP, Hui GS, Baisor M, Alpers MP, 1996. Assessment of the role of naturally acquired antibody levels to Plasmodium falciparum merozoite surface protein-1 in protecting Papua New Guinean children from malaria morbidity. Am J Trop Med Hyg 54 :443–448.

    • Search Google Scholar
    • Export Citation
  • 35

    Okenu DM, Riley EM, Bickle QD, Agomo PU, Barbosa A, Daugherty JR, Lanar DE, Conway DJ, 2000. Analysis of human antibodies to erythrocyte binding antigen 175 of Plasmodium falciparum. Infect Immun 68 :5559–5566.

    • Search Google Scholar
    • Export Citation
  • 36

    Felger I, Tavul L, Narara A, Genton B, Alpers M, Beck HP, 1995. The use of the polymerase chain reaction for more sensitive detection of Plasmodium falciparum. P N G Med J 38 :52–56.

    • Search Google Scholar
    • Export Citation
  • 37

    Holt DC, Fischer K, Tchavtchitch M, Wilson DW, Hauquitz NE, Hawthorne PL, Gardiner DL, Trenholme KR, Kemp DJ, 2001. Clags in Plasmodium falciparum and other species of Plasmodium. Mol Biochem Parasitol 118 :259–263.

    • Search Google Scholar
    • Export Citation
  • 38

    Bruce MC, Donnelly CA, Alpers MP, Galinski MR, Barnwell JW, Walliker D, Day KP, 2000. Cross-species interactions between malaria parasites in humans. Science 287 :845–848.

    • Search Google Scholar
    • Export Citation
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