ASSOCIATION OF INTERFERON-γ RESPONSES TO PRE-ERYTHROCYTIC STAGE VACCINE CANDIDATE ANTIGENS OF PLASMODIUM FALCIPARUM IN YOUNG KENYAN CHILDREN WITH IMPROVED HEMOGLOBIN LEVELS: XV. ASEMBO BAY COHORT PROJECT

JOHN M. O. ONG’ECHA Centre for Vector Biology and Control Research, Kenya Medical Research Institute, Kisumu, Kenya; Department of Zoology, Kenyatta University, Nairobi, Kenya; Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia; Unit of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

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ALTAF A. LAL Centre for Vector Biology and Control Research, Kenya Medical Research Institute, Kisumu, Kenya; Department of Zoology, Kenyatta University, Nairobi, Kenya; Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia; Unit of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

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DIANNE J. TERLOUW Centre for Vector Biology and Control Research, Kenya Medical Research Institute, Kisumu, Kenya; Department of Zoology, Kenyatta University, Nairobi, Kenya; Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia; Unit of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

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FEIKO O. TER KUILE Centre for Vector Biology and Control Research, Kenya Medical Research Institute, Kisumu, Kenya; Department of Zoology, Kenyatta University, Nairobi, Kenya; Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia; Unit of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

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SIMON K. KARIUKI Centre for Vector Biology and Control Research, Kenya Medical Research Institute, Kisumu, Kenya; Department of Zoology, Kenyatta University, Nairobi, Kenya; Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia; Unit of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

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VENKATCHALAM UDHAYAKUMAR Centre for Vector Biology and Control Research, Kenya Medical Research Institute, Kisumu, Kenya; Department of Zoology, Kenyatta University, Nairobi, Kenya; Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia; Unit of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

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ALLOYS S. S. ORAGO Centre for Vector Biology and Control Research, Kenya Medical Research Institute, Kisumu, Kenya; Department of Zoology, Kenyatta University, Nairobi, Kenya; Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia; Unit of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

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ALLEN W. HIGHTOWER Centre for Vector Biology and Control Research, Kenya Medical Research Institute, Kisumu, Kenya; Department of Zoology, Kenyatta University, Nairobi, Kenya; Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia; Unit of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

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BERNARD L. NAHLEN Centre for Vector Biology and Control Research, Kenya Medical Research Institute, Kisumu, Kenya; Department of Zoology, Kenyatta University, Nairobi, Kenya; Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia; Unit of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

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YA PING SHI Centre for Vector Biology and Control Research, Kenya Medical Research Institute, Kisumu, Kenya; Department of Zoology, Kenyatta University, Nairobi, Kenya; Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia; Unit of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

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Previous studies in animal models have revealed an association between interferon-γ (IFN- γ), produced by CD8+ T cells and irradiated sporozoite-induced sterile immunity. To determine whether IFN-γ can serve as a marker of pre-erythrocytic protective immunity in individuals naturally exposed to malaria, we characterized IFN-γ and lymphocyte proliferative responses to previously defined CD8+ cytotoxic T lymphocyte (CTL) epitopes from six pre-erythrocytic stage antigens in 107 children six months to two years old from a community-based birth cohort in western Kenya. We found that IFN- γ positive responders had higher hemoglobin (Hb) levels and significantly reduced prevalence of severe malarial anemia one month after the test compared with IFN- γ non-responders, suggesting that IFN- γ immune responses to these pre-erythrocytic antigens were associated with protection against malarial anemia. Children who responded by lymphocyte proliferation had a significantly longer time to first documented malaria parasitemia after birth; however, there was no correlation between the presence of lymphocyte proliferative response and higher Hb levels. We propose that IFN- γ production could be used as a potential marker of protective immunity against malaria associated anemia in young children living in malaria holoendemic areas.

  • 1

    World Health Organization, 2000. Expert Committee on Malaria. Twentieth Report. World Heatlh Organ Tech Rep Ser 892 :3.

  • 2

    Hoffman SL, Miller HL, 1996. Perspectives on malaria vaccine development. Hoffman SL, ed. Malaria Vaccine Development: A Multi-Immune Response Approach. Washington, DC: American Society for Microbiology, 1–13.

  • 3

    Weiss WR, Mellouk S, Houghten RA, Sedegah M, Kumar S, Good MF, Berzofsky JA, Miller LH, Hoffman SL, 1990. Cytotoxic T cells recognize a peptide from the circumsporozoite protein on malaria-infected hepatocytes. J Exp Med 171 :763–773.

    • Search Google Scholar
    • Export Citation
  • 4

    Aidoo M, Lalvani A, Allsopp CEM, Plebanski M, Meisner SJ, Krausa P, Browning M, Morris-Jones S, Gotch F, Fidock DA, Takiguchi M, Robson KJH, Greenwood BM, Druilhe P, Whittle HC, Hill AVS, 1995. Identification of conserved antigenic components of a cytotoxic T lymphocyte-inducing vaccine against malaria. Lancet 345 :1003–1007.

    • Search Google Scholar
    • Export Citation
  • 5

    Doolan DL, Hoffman SL, Southwood S, Wentworth PA, Sidney J, Chestnut RW, Keogh E, Appella E, Nutman TB, Lal AA, Gordon DM, Oloo A, Sette A, 1997. Degenerate cytotoxic T cell epitopes from Plasmodium falciparum restricted by multiple HLA-A and -B supertype alleles. Immunity 7 :97–112.

    • Search Google Scholar
    • Export Citation
  • 6

    Udhayakumar V, Ong’echa JM, Shi YP, Aidoo M, Orago ASS, Hawley WA, Nahlen BL, Hoffman SL, Weiss W, Lal AA, 1997. Cytotoxic T-cell reactivity and HLA-B35 binding of the variant Plasmodium falciparum circumsporozoite protein CD8+ CTL epitope in naturally exposed Kenyan adults. Eur J Immunol 27 :1952–1957.

    • Search Google Scholar
    • Export Citation
  • 7

    Aidoo M, Lalvani A, Gilbert SC, Hu JT, Daubersies P, Hurt N, Whittle HC, Druilhe P, Hill AV, 2000. Cytotoxic T-lymphocyte epitopes for HLA-B53 and other HLA-types in the malaria vaccine candidate liver-stage antigen 3. Infect Immun 68 :227–232.

    • Search Google Scholar
    • Export Citation
  • 8

    Hill AVS, Elvin J, Willis AC, Aidoo M, Allsopp CEM, Gotch FM, Ming Gao X, Takiguchi M, Greenwood BM, Townsend ARM, McMichael AJ, Whittle HC, 1992. Molecular analysis of the association of HLA-B53 and resistance to severe malaria. Nature 360 :434–439.

    • Search Google Scholar
    • Export Citation
  • 9

    Udhayakumar V, Shi YP, Kumar S, Jue DL, Wohlhueter RM, Lal AA, 1994. Antigenic diversity in the circumsporozoite protein of Plasmodium falciparum abrogates cytotoxic-T-cell recognition. Infect Immun 62 :1410–1413.

    • Search Google Scholar
    • Export Citation
  • 10

    Doolan DL, Hoffman SL, 1997. Multi-gene vaccination against malaria: a multi-stage, multi-immune response approach. Parasitol Today 13 :171–178.

    • Search Google Scholar
    • Export Citation
  • 11

    Ferreira A, Schofield L, Enea V, Schellekens H, van der Meide P, Collins W, Nussenzweig R, Nussenzweig V, 1986. Inhibition of development of exoerythrocytic forms of malaria parasites by gamma interferon. Science 232 :881–884.

    • Search Google Scholar
    • Export Citation
  • 12

    Mellouk S, Hoffman SL, Liu ZZ, De la Vega P, Billiar TR, Nussler AK, 1994. Nitric oxide-mediated antiplasmodial activity in human and murine hepatocytes induced by γ interferon and the parasite itself: enhancement by exogenous tetrahydrobiopterin. Infect Immun 62 :4043–4048.

    • Search Google Scholar
    • Export Citation
  • 13

    Seguin MC, Klotz FW, Schneider I, Weir JP, Goodbary M, Slayter M, Raney JJ, Aniagolu JU, Green SJ, 1994. Induction of nitric oxide synthase protects against malaria in mice exposed to irradiated Plasmodium berghei infected mosquitoes: involvement of interferon γ and CD8+ T cells. J Exp Med 180 :353–358.

    • Search Google Scholar
    • Export Citation
  • 14

    Doolan DL, Hoffman SL, 1999. IL-12 and NK cells are required for antigen-specific adaptive immunity against malaria initiated by CD8+ T cells in the Plasmodium yoelii model. J Immunol 163 :884–892.

    • Search Google Scholar
    • Export Citation
  • 15

    Gilbert SC, Plebanski M, Harris SJ, Allsopp CEM, Thomas R, Layton GT, Hill AVS, 1997. A protein particle vaccine containing multiple malaria epitopes. Nat Biotechnol 15 :1280–1284.

    • Search Google Scholar
    • Export Citation
  • 16

    Luty AJF, Lell B, Schmidt-Ott R, Lehman LG, Luckner D, Greve B, Matousek P, Herbich K, Schmid D, Migot-Nabias F, Deloron P, Nussenzweig RS, Kremsner PG, 1999. Interferon-γ responses are associated with resistance to reinfection with Plasmodium falciparum in young African children. J Infect Dis 179 :980–988.

    • Search Google Scholar
    • Export Citation
  • 17

    John CC, Sumba PO, Ouma JH, Nahlen BL, King CL, Kazura JW, 2000. Cytokine responses to Plasmodium falciparum liver-stage antigen 1 vary in rainy and dry seasons in highland Kenya. Infect Immun 68 :5198–5204.

    • Search Google Scholar
    • Export Citation
  • 18

    Kurtis JD, Lanar DE, Opollo M, Duffy PE, 1999. Interleukin-10 responses to liver-stage antigen 1 predict human resistance to Plasmodium falciparum.Infect Immun 67 :3424–3429.

    • Search Google Scholar
    • Export Citation
  • 19

    Connelly M, King CL, Bucci K, Walters S, Genton B, Alpers MP, Hollingdale M, Kazura JW, 1997. T-cell immunity to epitopes of liver-stage antigen 1 in an area of Papua New Guinea in which malaria is holoendemic. Infect Immun 65 :5082–5087.

    • Search Google Scholar
    • Export Citation
  • 20

    Lalvani A, Brookes R, Hambleton S, Britton WJ, Hill AV, McMichael AJ, 1997. Rapid effector function in CD8+ memory T cells. J Exp Med 186 :859–865.

    • Search Google Scholar
    • Export Citation
  • 21

    Altman JD, Moss PAH, Goulder PJR, Barouch DH, McHeyzer-Williams MG, Bell JI, McMichael AJ, Davis MM, 1996. Phenotypic analysis of antigen-specific T lymphocytes. Science 274 :94–96.

    • Search Google Scholar
    • Export Citation
  • 22

    Aidoo M, Udhayakumar V, 2000. Field studies of cytotoxic T lymphocytes in malaria infections: implications for malaria vaccine development. Parasitol Today 16 :52–57.

    • Search Google Scholar
    • Export Citation
  • 23

    Bloland PB, Ruebush TK, McCormick JB, Ayisi J, Boriga DA, Oloo AJ, Beach R, Hawley W, Lal A, Nahlen B, Udhayakumar V, Campbell CC, 1999. Longitudinal cohort study of the epidemiology of malaria infections in an area of intense malaria transmission I. Description of the study site, general methodology, and study population. Am J Trop Med Hyg 60 :635–640.

    • Search Google Scholar
    • Export Citation
  • 24

    Beier JC, Perkins PV, Onyango FK, Gargan TP, Oster CN, Whitmire RE, Koech DK, Roberts CR, 1990. Characterization of malaria transmission by Anopheles (Diptera: Culicidae) in western Kenya in preparation for malaria vaccine trials. J Med Entomol 27 :570–577.

    • Search Google Scholar
    • Export Citation
  • 25

    Bloland PB, Boriga DA, Ruebush TK, McCormick JB, Roberts JM, Oloo AJ, Hawley W, Lal A, Nahlen B, Campbell CC, 1999. Longitudinal cohort study of the epidemiology of malaria infections in an area of intense malaria transmission II. Description epidemiology of malaria infection and disease among children. Am J Trop Med Hyg 60 :641–648.

    • Search Google Scholar
    • Export Citation
  • 26

    Doolan DL, Houghten RA, Good MF, 1991. Assessment of human cytotoxic T cell activity using synthetic peptides: potential for field application. Pept Res 4 :125–131.

    • Search Google Scholar
    • Export Citation
  • 27

    Udhayakumar V, Anyona D, Kariuki S, Shi YP, Bloland PB, Branch OH, Weiss W, Nahlen BL, Kaslow DC, Lal AA, 1995. Identification of T and B cell epitopes recognized by humans in the C-terminal 42-Kda domain of the Plasmodium falciparum merozoite surface protein (MSP)-1. J Immunol 154 :6022–6030.

    • Search Google Scholar
    • Export Citation
  • 28

    Di Perri G, Bonora S, Vento S, Concia E, 1996. Naturally acquired immunity to Plasmodium falciparum.Parasitol Today 12 :346–347.

  • 29

    Riley EM, 1999. Is T-cell priming required for initiation of pathology in malaria infections? Immunol Today 20 :228–233.

  • 30

    Hill AVS, Allsopp CEM, Kwiatkowski D, Anstey NM, Twumasi P, Rowe PA, Bennett S, Brewster D, McMichael AJ, Greenwood BM, 1991. Common West African HLA antigens are associated with protection from severe malaria. Nature 352 :595–600.

    • Search Google Scholar
    • Export Citation
  • 31

    Mohan K, Stevenson MM, 1998. Interleukin-12 corrects severe anemia during blood-stage Plasmodium chabaudi AS in susceptible A/J mice. Exp Hematol 26 :45–52.

    • Search Google Scholar
    • Export Citation
  • 32

    Luty AJF, Perkins DJ, Lell B, Shmidt-Ott R, Lehman LG, Luckner D, Greve B, Matousek P, Herbich K, Schmid D, Weinberg JB, Kremsner PG, 2000. Low interleukin-12 activity in severe Plasmodium falciparum malaria. Infect Immun 68 :3909–3915.

    • Search Google Scholar
    • Export Citation
  • 33

    Doolan DL, Southwood Scott, Chesnut R, Appella E, Gomez E, Richards A, Higashimoto YI, Maewal A, Sidney J, Gramzinski RA, Mason C, Koech D, Hoffman SL, Sette A, 2000. HLA-DR-promiscuous T cell epitopes from Plasmodium falciparum pre-erythrocytic-stage antigens restricted by multiple HLA class II alleles. J Immunol 165: 1123–1137.

    • Search Google Scholar
    • Export Citation
  • 34

    Carlier Y, Truyens C, 1995. Influence of maternal infection on offspring resistance towards parasites. Parasitol Today 11 :94–99.

  • 35

    Le Hesran JY, Cot M, Personne P, Fievet N, Dobois B, Beyeme M, Boudin C, Deloron P, 1997. Maternal placental infection with Plasmodium falciparum and malaria morbidity during the first 2 years of life. Am J Epidemiol 146 :826–831.

    • Search Google Scholar
    • Export Citation
  • 36

    Hill AVS, 1992. Malaria resistant genes: natural selection. Trans R Soc Trop Med Hyg 86 :225–232.

  • 37

    Rasheed FN, Bulmer JN, Francisco ADE, Jawla MFB, Jakobson PH, Jepson A, Greenwood BM, 1995. Relationship between maternal malaria and malarial immune responses in mothers and neonates. Parasitology 17 :1–10.

    • Search Google Scholar
    • Export Citation
  • 38

    Zevering Y, Khamboonruang C, Rungeruengthanakit K, Tungviboonchai L, Ruengpipttanapan J, Bathurst I, Barr P, Good MF, 1994. Life-spans of human T-cell responses to determinants from circumsporozoite proteins of Plasmodium falciparum and Plasmodium vivax.Proc Natl Acad Sci USA. 91 :6118–6122.

    • Search Google Scholar
    • Export Citation
  • 39

    Ahmed R, Gray D, 1996. Immunological memory and protective immunity: understanding their relation. Science 272 :54–60.

  • 40

    Flanagan KL, Lee EA, Gravenor MB, Reece WH, Urban BC, Doherty T, Bojang KA, Pinder M, Hill AV, Plebanski M, 2001. Unique T cell effector functions elicited by Plasmodium falciparum epitopes in malaria-exposed Africans tested by three T cell assays. J Immunol 167 :4729–4737.

    • Search Google Scholar
    • Export Citation
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