1921
Volume 68, Issue 4
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Thrombospondin-related adhesive protein (TRAP) of is currently being tested in human vaccine studies. However, its natural reactivity in the field remains poorly characterized. More than 40% of 217 Kenyan donors responded in an interferon-γ (IFN-γ) enzyme-linked immunospot (ELISPOT) assay to at least one of 14 20mer peptides spanning 42% of the antigen. Reactivity was comparable from early childhood (>1 year of age) to old age, and the maximal precursor frequency of TRAP-specific cells to all 14 peptides was 1 in 4,000. Prospective follow-up for one year indicated that these low-level responses to TRAP did not protect against the subsequent development of malaria. Retesting of selected donors after one year showed a complete change in the reactivity pattern, suggesting that malaria-specific IFN-γ ELISPOT assay responses are short lived in naturally exposed donors, even to conserved epitopes. This study provides important information regarding natural reactivity to a key malaria antigen.

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2003-04-01
2017-09-26
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References

  1. Hoffman SL, Oster CN, Mason C, Beier JC, Sherwood JA, Ballou WR, Mugambi M, Chulay JD, 1989. Human lymphocyte proliferative response to a sporozoite T cell epitope correlates with resistance to falciparum malaria. J Immunol 142 : 1299–1303.
  2. Riley EM, Allen SJ, Bennett S, Thomas PJ, O’Donnell A, Lindsay SW, Good MF, Greenwood BM, 1990. Recognition of dominant T cell-stimulating epitopes from the circumsporozoite protein of Plasmodium falciparum and relationship to malaria morbidity in Gambian children. Trans R Soc Trop Med Hyg 84 : 648–657.
  3. Al-Yaman F, Genton B, Taraika J, Anders R, Alpers MP, 1997. Association between cellular response (IL-4) to RESA/Pf155 and protection from clinical malaria among Papua New Guinean children living in a malaria endemic area. Parasite Immunol 19 : 249–254.
  4. 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.
  5. 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.
  6. Migot-Nabias F, Deloran P, Ringwald P, Dubois B, Mayombo J, Minh TN, Fievet N, Millet P, 2000. Immune response to Plasmodium falciparum liver stage antigen-1: geographical variations within Central Africa and their relationship with protection from clinical malaria. Trans R Soc Trop Med Hyg 94 : 557–562.
  7. Ferreira A, Schofield L, Enea V, Schellekens H, van der Meide P, Collins WE, Nussenzweig RS, Nussenzweig V, 1986. Inhibition of development of exoerythrocytic forms of malaria parasites by interferon-gamma. Science 232 : 881–884.
  8. Schofield L, Ferreira A, Altszuler R, Nussenzweig V, Nussenzweig RS, 1987. Interferon-gamma inhibits the intrahepatocytic development of malaria parasites in vitro. J Immunol 139 : 2020–2025.
  9. Mellouk S, Green S, Nacy C, Hoffman SL, 1991. IFN-gamma inhibits development of Plasmodium berghei exoerythrocytic stages in hepatocytes by an L-arginine-dependent effector mechanism. J Immunol 146 : 3971–3976.
  10. Flanagan KL, Plebanski M, Akinwunmi P, Lee EAM, Reece WHH, Robson KJH, Hill AVS, Pinder M, 1999. Broadly distributed T cell reactivity, with no immunodominant loci, to the pre-erythrocytic antigen thrmobospondin-related adhesive protein of Plasmodium falciparum in West Africans. Eur J Immunol 29 : 1943–1954.
  11. Flanagan KL, Lee EAM, Gravenor MB, Reece WHH, Urban BC, Doherty T, Bojang KA, Pinder M, Hill AVS, 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.
  12. Lee EAM, Flanagan KL, Odhiambo K, Reece WHH, Potter CG, Bailey R, Marsh K, Pinder M, Hill AVS, Plebanski M, 2001. Identification of frequently recognized dimorphic T-cell epitopes in Plasmodium falciparum merozoite surface protein-1 in West and East Africans: lack of correlation of immune recognition and allelic prevalence. Am J Trop Med Hyg 64 : 194–203.
  13. Reece WHH, Plebanski M, Akinwunmi P, Gothard P, Flanagan KL, Lee EAM, Cortina-Borja M, Hill AVS, Pinder M, 2002. Naturally exposed populations differ in their T1 and T2 responses to the circumsporozoite protein of Plasmodium falciparum. Infect Immun 70 : 1468–1474.
  14. Schneider J, Gilbert SC, Blanchard TJ, Hanke T, Robson KJH, Hannan CM, Becker M, Sinden R, Smith GL, Hill AVS, 1998. Enhanced immunogenicity for CD8+ T cell induction and complete protective efficacy of malaria DNA vaccination by boosting with modified vaccinia virus Ankara. Nat Med 4 : 397–402.
  15. Plebanski M, Gilbert SC, Schneider J, Hannan CM, Layton G, Blanchard T, Becker M, Smith G, Butcher G, Sinden RE, Hill AVS, 1998. Protection from Plasmodium berghei infection by priming and boosting T cells to a single class-I-restricted epitope with recombinant carriers suitable for human use. Eur J Immunol 28 : 1–11.
  16. Stoute JA, Slaoui M, Gray Heppner D, Momin P, Kester KE, Desmons P, Wellde BT, Garçon N, Krzych U, Marchand M, Ballou WR, Cohen JD, 1997. A preliminary evaluation of a recombinant circumsporozoite protein vaccine against Plasmodium falciparum malaria. N Engl J Med 336 : 86–91.
  17. Robson KJH, Hall JRS, Jennings MW, Harris TJR, Marsh K, Newbold CI, Tate VE, Weatherall DJ, 1988. A highly conserved amino-acid sequence in thrombospondin, properdin and in proteins from sporozoites and blood stages of a human malaria parasite. Nature 355 : 79–82.
  18. Rogers WO, Malik A, Mellouk S, Nakamura K, Rogers MD, Szarfman A, Gordon DM, Nussler AK, Aikawa M, Hoffman SL, 1992. Characterization of Plasmodium falciparum sporozoite surface protein 2. Proc Natl Acad Sci USA 89 : 9176–9180.
  19. Gannt S, Persson C, Rose K, Birkett AJ, Abagyan R, Nussenzweig V, 2000. Antibodies against thrombospondin-related anonymous protein do not inhibit Plasmodium sporozoite infectivity in vivo. Infect Immun 68 : 3667–3673.
  20. Sultan AA, Thathy V, Frevert U, Robson KJH, Crisanti A, Nussenzweig V, Nussenzwig RS, Menard R, 1997. TRAP is necessary for gliding motility and infectivity of sporozoites. Cell 90 : 511–522.
  21. Müller H-M, Reckmann I, Hollingdale MR, Bujard H, Robson KJH, Crisanti A, 1993. Thrombospondin related anonymous protein (TRAP) of Plasmodium falciparum binds specifically to sulfated glycoconjugates and to HepG2 hepatoma cells suggesting a role for this molecule in sporozoite invasion of hepatocytes. EMBO J 12 : 2881–2889.
  22. Khusmith S, Sedegah M, Hoffman SL, 1994. Complete protection against Plasmodium yoelii by adoptive transfer of a CD8+ cytotoxic T-cell clone recognizing the sporozoite surface protein 2. Infect Immun 62 : 2979–2983.
  23. Khusmith S, Charoenvit Y, Kumar S, Sedegah M, Beaudoin RL, Hoffman SL, 1991. Protection against malaria by vaccination with sporozoite surface protein 2 plus CS protein. Science 252 : 715–718.
  24. Wang R, Charoenvit Y, Corradin G, De La Vega P, Franke ED, Hoffman SL, 1996. Protection against malaria by Plasmodium yoelii sporozoite surface protein 2 linear peptide induction of CD4+ T cell- and IFN-gamma-dependent elimination of infected hepatocytes. J Immunol 157 : 4061–4067.
  25. 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, Druihle P, Whittle HC, Hill AVS, 1995. Identification of conserved antigenic components for a cytotoxic T lymphocyte-inducing vaccine against malaria. Lancet 345 : 1003–1007.
  26. Wizel B, Houghten RA, Church P, Tine JA, Lanar DE, Gordon DM, Ballou WR, Sette A, Hoffman SL, 1995. HLA-A2-restricted cytotoxic T lymphocyte responses to multiple Plasmodium falciparum Sporozoite Surface Protein 2 epitopes in sporozoite-immunized volunteers. J Immunol 155 : 766–775.
  27. Doolan DL, Hoffman SL, Southwood S, Wentworth PA, Sidney J, Chesnut RW, Keogh E, Apella E, Nutman TB, Lal AA, Gordon DM, Oloo A, Sette A, 1997. Degenerate cytotoxic T cell epitopes from P. falciparum restricted by multiple HLA-A and HLA-B supertype alleles. Immunity 7 : 97–112.
  28. Scarselli E, Tölle R, Koita O, Diallo M, Müller H-M, Früh K, Doumbo O, Crisanti A, Bujard H, 1993. Analysis of the human antibody responses to thrombospondin-related anonymous protein of Plasmodium falciparum. Infect Immun 61 : 3490–3495.
  29. Dolo A, Modiano D, Doumbo O, Bosman A, Sidibe T, Keita MM, Naitza S, Robson KJ, Crisanti A, 1999. Thrombospondin related adhesive protein (TRAP), a potential malaria vaccine candidate. Parassitologia 41 : 425–428.
  30. Mbogo CN, Snow RW, Khamala CP, Kabiru EW, Ouma JH, Githure JI, Marsh K, Beier JC, 1995. Relationship between Plasmodium falciparum transmission by vector populations and the incidence of severe disease at nine sites on the Kenyan coast. Am J Trop Med Hyg 52 : 201–206.
  31. Good MF, Pombo D, Quakyi IA, Riley EM, Houghten RA, Menon A, Alling DW, Berzofsky JA, Miller LH, 1988. Human T-cell recognition of the circumsporozoite protein of Plasmodium falciparum: immunodominant T-cell domains map to the polymorphic regions of the molecule. Proc Natl Acad Sci USA 85 : 1199.
  32. Robson KJH, Hall JRS, Davies LC, Crisanti A, Hill AVS, Wellems TE, 1990. Polymorphism of the TRAP gene of Plasmodium falciparum. Proc R Soc Lond B Biol Sci 242: 205–216.
  33. Bonelo A, Valmori D, Triponez F, Tiercy JM, Mentha G, Oberholzer J, Champagne P, Romero JF, Esposito F, Nebie I, Barbey C, Romero P, Herrera S, Corradin G, Lopez JA, 2000. Generation and characterization of malaria-specific human CD8(+) lymphocyte clones: effect of natural polymorphism on T cell recognition and endogenous cognate antigen presentation by liver cells. Eur J Immunol 30 : 3079–3088.
  34. Bucci K, Kastens W, Hollingdale MR, Shanker A, Alpers MP, King CL, Kazura JW, 2000. Influence of age and HLA type on interferon-gamma (IFN-γ) responses to a naturally occurring polymorphic epitope of Plasmodium falciparum liver stage antigen-1 (LSA-1). Clin Exp Immunol 122 : 94–100.
  35. Wang R, Epstein J, Baraceros FM, Gorak EJ, Charoenvit Y, Carucci DJ, Hedstrom RC, Rahardjo N, Gay T, Hobart P, Stout R, Jones TR, Richie TL, Parker SE, Doolan DL, Norman J, Hoffman SL, 2001. Induction of CD4(+) T cell-dependent CD8(+) type 1 responses in humans by a malaria DNA vaccine. Proc Natl Acad Sci USA 98 : 10817–10822.
  36. Fievet N, Ringwald P, Bickii J, Dubois B, Maubert B, Le Hesran JY, Cot M, Deloran P, 1996. Malaria cellular immune responses in neonates from Cameroon. Parasite Immunol 18 : 483–490.
  37. Al-Yaman F, Genton B, Taraika J, Anders R, Alpers MP, 1997. Cellular immunity to merozoite surface protein 2 (FC27 and 3D7) in Papua New Guinean children. Temporal variation and relation to clinical and parasitological status. Parasite Immunol 19 : 207–214.
  38. 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.
  39. Lalvani A, Moris P, Voss G, Pathan AA, Kester KE, Brookes R, Lee E, Koutsoukos M, Plebanski M, Delchambre M, Flanagan KL, Carton C, Slaoui M, van Hoecke C, Ballou WR, Hill AVS, Cohen J, 1999. Potent induction of focused Th1-type cellular and humoral immune responses by RTS,S/SBAS2, a recombinant Plasmodium falciparum malaria vaccine. J Infect Dis 180 : 1656–1664.
  40. Theander TG, Bygberg IC, Andersen BJ, Jepsen S, Kharazmi A, Ødum N, 1986. Suppression of parasite-specific response in Plasmodium falciparum malaria. A longitudinal study of blood mononuclear cell proliferation and subset composition. Scand J Immunol 24 : 73–81.
  41. Troye-Blomberg M, Riley EM, Perlmann H, Andersson G, Snow RW, Allen SJ, Houghten RA, Olerup O, Greenwood BM, Perlmann P, 1989. T- and B-cell responses of Plasmodium falciparum malaria-immune individuals to synthetic peptides corresponding to epitopes in the conserved repeat regions of the P. falciparum antigen Pf155/RESA. J Immunol 25 : 1002–1008.
  42. Riley EM, Morris-Jones S, Blackman MJ, Greenwood BM, Holder AA, 1993. A longitudinal study of naturally acquired cellular and humoral immune responses to a merozoite surface protein (MSP1) of Plasmodium falciparum in an area of seasonal malaria transmission. Parasite Immunol 15 : 513–524.
  43. Ho M, Webster HK, Looareesuwan S, Supanaranond W, Phillips RE, Chanthavanich P, Warrell DA, 1986. Antigen-specific immunosuppression in human malaria due to Plasmodium falciparum. J Infect Dis 153 : 763–771.
  44. Theander TG, Bygberg IC, Jacobsen L, Jepsen S, Larsen PB, Kharazmi A, 1986. Low parasite specific T cell response in clinically immune individuals with low grade Plasmodium falciparum parasitaemia. Trans R Soc Trop Med Hyg 80 : 1000–1001.
  45. Hviid L, Theander TG, Abu Zeid YA, Abdulhadi NH, Jakobsen PH, Saeed BO, Jepsen S, Bayoumi RA, Jensen JB, 1991. Loss of cellular immune reactivity during acute Plasmodium falciparum malaria. FEMS Microbiol Immunol 3 : 219–227.
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  • Received : 30 Sep 2002
  • Accepted : 26 Dec 2002

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