WHO, 2000. Malaria—A Global Crisis. Geneva: WHO.
Nussenzweig V, Nussenzweig RS, 1989. Rationale for the development of an engineered sporozoite malaria vaccine. Adv Immunol 45 :283–334.
Hoffman SL, Goh LM, Luke TC, Schneider I, Le TP, Doolan DL, Sacci J, de la Vega P, Dowler M, Paul C, Gordon DM, Stoute JA, Church LW, Sedegah M, Heppner DG, Ballou WR, Richie TL, 2002. Protection of humans against malaria by immunization with radiation-attenuated Plasmodium falciparum sporozoites. J Infect Dis 185 :1155–1164.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Reece WH, Pinder M, Gothard PK, Milligan P, Bojang K, Doherty T, Plebanski M, Akinwunmi P, Everaere S, Watkins KR, Voss G, Tornieporth N, Alloueche A, Greenwood BM, Kester KE, McAdam KP, Cohen J, Hill AV, 2004. A CD4(+) T-cell immune response to a conserved epitope in the circumsporozoite protein correlates with protection from natural Plasmodium falciparum infection and disease. Nat Med 10 :406–410.
McConkey SJ, Moorthy VS, Webster D, Dunachie S, Butcher G, Vuola JM, Blanchard TJ, Gothard P, Watkins K, Hannan CM, Everaere S, Brown K, Kester KE, Cummings J, Williams J, Heppner DG, Pathan A, Flanagan K, Arulanantham N, Roberts MT, Roy M, Smith GL, Schneider J, Peto T, Sinden RE, Gilbert SC, Hill AV, 2003. Enhanced T-cell immunogenicity of plasmid DNA vaccines boosted by recombinant modified vaccinia Ankara in humans. Nat Med 9 :729–735.
Moorthy VS, Imoukhuede EB, Milligan P, Bojang K, Keating S, Kaye P, Pinder M, Gilbert SC, Walraven G, Greenwood BM, Hill AV, 2004. A randomised, double-blind, controlled vaccine efficacy trial of DNA/MVA ME-TRAP against malaria infection in Gambian adults. PLOS Med 33 :128–136.
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 thrombospondin-related adhesive protein of Plasmodium falciparum in West Africans. Eur J Immunol 29 :1943–1954.
Schofield L, Villaquiran J, Ferreira A, Schellekens H, Nussenzweig R, Nussenzweig V, 1987. Gamma-Interferon, CD8+ T cells and antibodies required for immunity to malaria sporozoites. Nature (Lond) 330 :664–666.
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.
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.
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 gamma and CD8+ T cells. J Exp Med 180 :353–358.
Mellouk SO, Hoffman SL, Liu ZZ, de la Vega P, Billar TR, Nussler AK, 1994. Nitric oxide-mediated antiplasmodial activity in human and murine hepatocytes induced by gamma interferon and the parasite itself: enhancement by exogenous tetrahydrobiopterin. Infect Immun 62 :4043–4046.
Robson KJH, Hall JRS, Davies LC, Crisanti A, Hill AVS, Wellems TE, 1990. Polymorphism of the TRAP gene of Plasmodium falciparum. Proc R Soc 242 :205–216.
Robson KJH, Dolo A, Hackford IR, Doumbo O, Richards MB, Keita MM, Sidibi T, Bosman A, Modiano D, Crisanti A, 1998. Natural polymorphism of the thrombospondin-related adhesive protein of Plasmodium falciparum. Am J Trop Med Hyg 58 :81–89.
Robson KJH, 1993. Approaches to studying genetic diversity of Plasmodium falciparum using DNA sequence variation. Parasitologia 35 (Suppl):91–94.
Bunce M, O’Neill CM, Barnardo MCNM, Krausa P, Browning MJ, Morris PJ, Welsh KI, 1995. Phototyping: comprehensive DNA typing for HLA-A, B, C, DRB1, DRB3, DRB4, DRB5 & DQB1 by PCR with 144 primer mixes utilising sequence-specific primers (PCR-SSP). Tissue Antigens 46 :355–367.
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.
Doolan DL, Southwood S, Chesnut R, Apella 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.
Flanagan KL, Mwangi T, Plebanski M, Odhiambo K, Ross A, Kinyanjui S, Kortok M, Lowe B, Sheu E, Marsh K, Hill AVS, 2003. Ex vivo interferon gamma immune response to TRAP in coastal Kenyans: longevity and risk of P. falciparum infection. Am J Trop Med Hyg 68 :421–430.
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.
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 :1199–1203.
Kabilan L, Troye-Blomberg M, Perlmann H, Andersson G, Hogh B, Peterson E, Bjorkmann A, Perlmann P, 1988. T-cell epitopes in Pf155/RESA, a major candidate for a Plasmodium falciparum malaria vaccine. Proc Natl Acad Sci USA 85 :5659–5663.
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.
Perlaza BL, Sauzet JP, Balde AT, Brahimi K, Tall A, Corradin G, Druilhe P, 2001. Long synthetic peptides encompassing the Plasmodium falciparum LSA-3, the target of human B and T cells and are potent inducers of B helper, T helper and cytolytic T cell responses in mice. Eur J Immunol 31 :2200–2209.
Vanderlugt CL, Begolka WS, Neville KL, Katz-Levy Y, Howard LM, Eagar TN, Bluestone J, Miller SD, 1998. The functional significance of epitope spreading and its regulation by co-stimulatory molecules. Immunol Rev 164 :63–72.
Vanderlugt CL, Miller SD, 2002. Epitope spreading in immune-mediated diseases: implications for immunotherapy. Nat Rev Immunol 2 :85–95.
Plebanski M, Flanagan KL, Lee EAM, Reece WHH, Hart K, Gelder C, Gillespie G, Pinder M, Hill AVS, 1999. Interleukin 10-mediated immunosuppression by a variant CD4 T cell epitope of Plasmodium falciparum. Immunity 10 :651–660.
de la Cruz V, Maloy WL, Miller LH, Lal AA, Good MF, Mc-Cutchan TF, 1988. Lack of cross-reactivity between variant T cell determinants from malaria circumsporozoite protein. J Immunol 141 :2456–2460.
Zevering Y, Khamboonruang C, Good MF, 1994. Natural amino acid polymorphisms of the circumsporozoite protein of Plasmodium falciparum abrogate specific human CD4+ T cell responsiveness. Eur J Immunol 24 :1418–1425.
Groux H, Powrie F, 1999. Regulatory T cells and inflammatory bowel disease. Immunol Today 20 :442–444.
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Malaria vaccines based on thrombospondin-related adhesive protein of Plasmodium falciparum (Pf TRAP) are currently undergoing clinical trials in humans. This study was designed to investigate naturally acquired cellular immunity to Pf TRAP in adults from a target population for future trials of TRAP-based vaccines in Kilifi, Kenya. We first tested reactivity to a panel of 53 peptides spanning Pf TRAP and identified 26 novel T-cell epitopes. A panel of naturally occurring polymorphic variant epitope peptides were made to the most commonly recognized epitope regions and tested for ability to elicit IFN-γ, IL-4, and IL-10 production. These data provide for the first time a complex cytokine matrix mapping naturally induced T-cell responses to TRAP and suggest that T-cell responses boosted by vaccination with Pf TRAP could stimulate the release of competing pro- and anti-inflammatory cytokines. They further define polymorphic variants able to boost specific Th1, Th2, and possibly Tr1 reactivity.
WHO, 2000. Malaria—A Global Crisis. Geneva: WHO.
Nussenzweig V, Nussenzweig RS, 1989. Rationale for the development of an engineered sporozoite malaria vaccine. Adv Immunol 45 :283–334.
Hoffman SL, Goh LM, Luke TC, Schneider I, Le TP, Doolan DL, Sacci J, de la Vega P, Dowler M, Paul C, Gordon DM, Stoute JA, Church LW, Sedegah M, Heppner DG, Ballou WR, Richie TL, 2002. Protection of humans against malaria by immunization with radiation-attenuated Plasmodium falciparum sporozoites. J Infect Dis 185 :1155–1164.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Reece WH, Pinder M, Gothard PK, Milligan P, Bojang K, Doherty T, Plebanski M, Akinwunmi P, Everaere S, Watkins KR, Voss G, Tornieporth N, Alloueche A, Greenwood BM, Kester KE, McAdam KP, Cohen J, Hill AV, 2004. A CD4(+) T-cell immune response to a conserved epitope in the circumsporozoite protein correlates with protection from natural Plasmodium falciparum infection and disease. Nat Med 10 :406–410.
McConkey SJ, Moorthy VS, Webster D, Dunachie S, Butcher G, Vuola JM, Blanchard TJ, Gothard P, Watkins K, Hannan CM, Everaere S, Brown K, Kester KE, Cummings J, Williams J, Heppner DG, Pathan A, Flanagan K, Arulanantham N, Roberts MT, Roy M, Smith GL, Schneider J, Peto T, Sinden RE, Gilbert SC, Hill AV, 2003. Enhanced T-cell immunogenicity of plasmid DNA vaccines boosted by recombinant modified vaccinia Ankara in humans. Nat Med 9 :729–735.
Moorthy VS, Imoukhuede EB, Milligan P, Bojang K, Keating S, Kaye P, Pinder M, Gilbert SC, Walraven G, Greenwood BM, Hill AV, 2004. A randomised, double-blind, controlled vaccine efficacy trial of DNA/MVA ME-TRAP against malaria infection in Gambian adults. PLOS Med 33 :128–136.
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 thrombospondin-related adhesive protein of Plasmodium falciparum in West Africans. Eur J Immunol 29 :1943–1954.
Schofield L, Villaquiran J, Ferreira A, Schellekens H, Nussenzweig R, Nussenzweig V, 1987. Gamma-Interferon, CD8+ T cells and antibodies required for immunity to malaria sporozoites. Nature (Lond) 330 :664–666.
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.
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.
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 gamma and CD8+ T cells. J Exp Med 180 :353–358.
Mellouk SO, Hoffman SL, Liu ZZ, de la Vega P, Billar TR, Nussler AK, 1994. Nitric oxide-mediated antiplasmodial activity in human and murine hepatocytes induced by gamma interferon and the parasite itself: enhancement by exogenous tetrahydrobiopterin. Infect Immun 62 :4043–4046.
Robson KJH, Hall JRS, Davies LC, Crisanti A, Hill AVS, Wellems TE, 1990. Polymorphism of the TRAP gene of Plasmodium falciparum. Proc R Soc 242 :205–216.
Robson KJH, Dolo A, Hackford IR, Doumbo O, Richards MB, Keita MM, Sidibi T, Bosman A, Modiano D, Crisanti A, 1998. Natural polymorphism of the thrombospondin-related adhesive protein of Plasmodium falciparum. Am J Trop Med Hyg 58 :81–89.
Robson KJH, 1993. Approaches to studying genetic diversity of Plasmodium falciparum using DNA sequence variation. Parasitologia 35 (Suppl):91–94.
Bunce M, O’Neill CM, Barnardo MCNM, Krausa P, Browning MJ, Morris PJ, Welsh KI, 1995. Phototyping: comprehensive DNA typing for HLA-A, B, C, DRB1, DRB3, DRB4, DRB5 & DQB1 by PCR with 144 primer mixes utilising sequence-specific primers (PCR-SSP). Tissue Antigens 46 :355–367.
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.
Doolan DL, Southwood S, Chesnut R, Apella 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.
Flanagan KL, Mwangi T, Plebanski M, Odhiambo K, Ross A, Kinyanjui S, Kortok M, Lowe B, Sheu E, Marsh K, Hill AVS, 2003. Ex vivo interferon gamma immune response to TRAP in coastal Kenyans: longevity and risk of P. falciparum infection. Am J Trop Med Hyg 68 :421–430.
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.
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 :1199–1203.
Kabilan L, Troye-Blomberg M, Perlmann H, Andersson G, Hogh B, Peterson E, Bjorkmann A, Perlmann P, 1988. T-cell epitopes in Pf155/RESA, a major candidate for a Plasmodium falciparum malaria vaccine. Proc Natl Acad Sci USA 85 :5659–5663.
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.
Perlaza BL, Sauzet JP, Balde AT, Brahimi K, Tall A, Corradin G, Druilhe P, 2001. Long synthetic peptides encompassing the Plasmodium falciparum LSA-3, the target of human B and T cells and are potent inducers of B helper, T helper and cytolytic T cell responses in mice. Eur J Immunol 31 :2200–2209.
Vanderlugt CL, Begolka WS, Neville KL, Katz-Levy Y, Howard LM, Eagar TN, Bluestone J, Miller SD, 1998. The functional significance of epitope spreading and its regulation by co-stimulatory molecules. Immunol Rev 164 :63–72.
Vanderlugt CL, Miller SD, 2002. Epitope spreading in immune-mediated diseases: implications for immunotherapy. Nat Rev Immunol 2 :85–95.
Plebanski M, Flanagan KL, Lee EAM, Reece WHH, Hart K, Gelder C, Gillespie G, Pinder M, Hill AVS, 1999. Interleukin 10-mediated immunosuppression by a variant CD4 T cell epitope of Plasmodium falciparum. Immunity 10 :651–660.
de la Cruz V, Maloy WL, Miller LH, Lal AA, Good MF, Mc-Cutchan TF, 1988. Lack of cross-reactivity between variant T cell determinants from malaria circumsporozoite protein. J Immunol 141 :2456–2460.
Zevering Y, Khamboonruang C, Good MF, 1994. Natural amino acid polymorphisms of the circumsporozoite protein of Plasmodium falciparum abrogate specific human CD4+ T cell responsiveness. Eur J Immunol 24 :1418–1425.
Groux H, Powrie F, 1999. Regulatory T cells and inflammatory bowel disease. Immunol Today 20 :442–444.
Past two years | Past Year | Past 30 Days | |
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Abstract Views | 20 | 20 | 9 |
Full Text Views | 238 | 76 | 0 |
PDF Downloads | 40 | 13 | 0 |