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Pre-erythrocytic Immunity in Malaria

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  • Agnandji ST, Fendel R, Mestre M, Janssens M, Vekemans J, Held J, Gnansounou F, Haertle S, von Glasenapp I, Oyakhirome S, Mewono L, Moris P, Lievens M, Demoitie MA, Dubois PM, Villafana T, Jongert E, Olivier A, Cohen J, Esen M, Kremsner PG, Lell B, Mordmuller B. Induction of Plasmodium falciparum-specific CD4+ T cells and memory B cells in Gabonese children vaccinated with RTS,S/AS01(E) and RTS,S/AS02(D). PLoS One. 2011;6(4):e18559.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Belz GT, Smith CM, Kleinert L, Reading P, Brooks A, Shortman K, Carbone FR, Heath WR. Distinct migrating and nonmigrating dendritic cell populations are involved in MHC class I-restricted antigen presentation after lung infection with virus. Proc Natl Acad Sci U S A. 2004;101(23):8670–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bergmann-Leitner ES, Mease RM, De La Vega P, Savranskaya T, Polhemus M, Ockenhouse C, Angov E. Immunization with pre-erythrocytic antigen CelTOS from Plasmodium falciparum elicits cross-species protection against heterologous challenge with Plasmodium berghei. PLoS One. 2010;5(8):e12294.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bijker EM, Bastiaens GJ, Teirlinck AC, van Gemert GJ, Graumans W, van de Vegte-Bolmer M, Siebelink-Stoter R, Arens T, Teelen K, Nahrendorf W, Remarque EJ, Roeffen W, Jansens A, Zimmerman D, Vos M, van Schaijk BC, Wiersma J, van der Ven AJ, de Mast Q, van Lieshout L, Verweij JJ, Hermsen CC, Scholzen A, Sauerwein RW. Protection against malaria after immunization by chloroquine prophylaxis and sporozoites is mediated by preerythrocytic immunity. Proc Natl Acad Sci U S A. 2013;110(19):7862–7.

    Article  PubMed  PubMed Central  Google Scholar 

  • Casares S, Brumeanu TD, Richie TL. The RTS,S malaria vaccine. Vaccine. 2010;28(31):4880–94.

    Article  CAS  PubMed  Google Scholar 

  • Chakravarty S, Cockburn IA, Kuk S, Overstreet MG, Sacci JB, Zavala F. CD8+ T lymphocytes protective against malaria liver stages are primed in skin-draining lymph nodes. Nat Med. 2007;13(9):1035–41.

    Article  CAS  PubMed  Google Scholar 

  • Cockburn IA, Amino R, Kelemen RK, Kuo SC, Tse SW, Radtke A, Mac-Daniel L, Ganusov VV, Zavala F, Menard R. In vivo imaging of CD8+ T cell-mediated elimination of malaria liver stages. Proc Natl Acad Sci U S A. 2013;110(22):9090–5.

    Article  PubMed  PubMed Central  Google Scholar 

  • Cummings JF, Spring MD, Schwenk RJ, Ockenhouse CF, Kester KE, Polhemus ME, Walsh DS, Yoon IK, Prosperi C, Juompan LY, Lanar DE, Krzych U, Hall BT, Ware LA, Stewart VA, Williams J, Dowler M, Nielsen RK, Hillier CJ, Giersing BK, Dubovsky F, Malkin E, Tucker K, Dubois MC, Cohen JD, Ballou WR, Heppner Jr DG. Recombinant Liver Stage Antigen-1 (LSA-1) formulated with AS01 or AS02 is safe, elicits high titer antibody and induces IFN-gamma/IL-2 CD4+ T cells but does not protect against experimental Plasmodium falciparum infection. Vaccine. 2010;28(31):5135–44.

    Article  CAS  PubMed  Google Scholar 

  • da Silva HB, Caetano SS, Monteiro I, Gomez-Conde I, Hanson K, Penha-Goncalves C, Olivieri DN, Mota MM, Marinho CR, D’Imperio Lima MR, Tadokoro CE. Early skin immunological disturbance after Plasmodium-infected mosquito bites. Cell Immunol. 2012;277(1–2):22–32.

    Article  CAS  PubMed  Google Scholar 

  • Depinay N, Hacini F, Beghdadi W, Peronet R, Mecheri S. Mast cell-dependent down-regulation of antigen-specific immune responses by mosquito bites. J Immunol. 2006;176(7):4141–6.

    Article  CAS  PubMed  Google Scholar 

  • Duffy PE, Sahu T, Akue A, Milman N, Anderson C. Pre-erythrocytic malaria vaccines: identifying the targets. Expert Rev Vaccines. 2012;11(10):1261–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dups JN, Pepper M, Cockburn IA. Antibody and B cell responses to Plasmodium sporozoites. Front Microbiol. 2014;5:625.

    Article  PubMed  PubMed Central  Google Scholar 

  • Epstein JE, Tewari K, Lyke KE, Sim BK, Billingsley PF, Laurens MB, Gunasekera A, Chakravarty S, James ER, Sedegah M, Richman A, Velmurugan S, Reyes S, Li M, Tucker K, Ahumada A, Ruben AJ, Li T, Stafford R, Eappen AG, Tamminga C, Bennett JW, Ockenhouse CF, Murphy JR, Komisar J, Thomas N, Loyevsky M, Birkett A, Plowe CV, Loucq C, Edelman R, Richie TL, Seder RA, Hoffman SL. Live attenuated malaria vaccine designed to protect through hepatic CD8(+) T cell immunity. Science. 2011;334(6055):475–80.

    Article  CAS  PubMed  Google Scholar 

  • Ewer KJ, O’Hara GA, Duncan CJ, Collins KA, Sheehy SH, Reyes-Sandoval A, Goodman AL, Edwards NJ, Elias SC, Halstead FD, Longley RJ, Rowland R, Poulton ID, Draper SJ, Blagborough AM, Berrie E, Moyle S, Williams N, Siani L, Folgori A, Colloca S, Sinden RE, Lawrie AM, Cortese R, Gilbert SC, Nicosia A, Hill AV. Protective CD8+ T-cell immunity to human malaria induced by chimpanzee adenovirus-MVA immunisation. Nat Commun. 2013;4:2836.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Frevert U, Krzych U. Plasmodium cellular effector mechanisms and the hepatic microenvironment. Front Microbiol. 2015;6:482.

    PubMed  PubMed Central  Google Scholar 

  • Frevert U, Usynin I, Baer K, Klotz C. Plasmodium sporozoite passage across the sinusoidal cell layer. Subcell Biochem. 2008;47:182–97.

    Article  PubMed  Google Scholar 

  • Gantt S, Persson C, Rose K, Birkett AJ, Abagyan R, Nussenzweig V. Antibodies against thrombospondin-related anonymous protein do not inhibit Plasmodium sporozoite infectivity in vivo. Infect Immun. 2000;68(6):3667–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guilbride DL, Gawlinski P, Guilbride PD. Why functional pre-erythrocytic and bloodstage malaria vaccines fail: a meta-analysis of fully protective immunizations and novel immunological model. PLoS One. 2010;5(5):e10685.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Haeberlein S, Chevalley-Maurel S, Ozir-Fazalalikhan A, Koppejan H, Winkel BMF, Ramesar J, Khan SM, Sauerwein RW, Roestenberg M, Janse CJ, Smits HH, Franke-Fayard B. Protective immunity differs between routes of administration of attenuated malaria parasites independent of parasite liver load. Sci Rep. 2017;7(1):10372.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hafalla JC, Bauza K, Friesen J, Gonzalez-Aseguinolaza G, Hill AV, Matuschewski K. Identification of targets of CD8(+) T cell responses to malaria liver stages by genome-wide epitope profiling. PLoS Pathog. 2013;9(5):e1003303.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hart GT, Theorell J, Tran T, Arora G, Crompton PD, Bryceson Y, Long EO. Antibody-dependent NK cell control of Plasmodium falciparum infection. J Immunol. 2017;198(1 Suppl):68.19.

    Google Scholar 

  • Hollingdale MR, Sedegah M. Development of whole sporozoite malaria vaccines. Expert Rev Vaccines. 2017;16(1):45–54.

    Article  CAS  PubMed  Google Scholar 

  • Hopp CS, Sinnis P. The innate and adaptive response to mosquito saliva and Plasmodium sporozoites in the skin. Ann N Y Acad Sci. 2015;1342:37–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ishizuka AS, Lyke KE, DeZure A, Berry AA, Richie TL, Mendoza FH, Enama ME, Gordon IJ, Chang LJ, Sarwar UN, Zephir KL, Holman LA, James ER, Billingsley PF, Gunasekera A, Chakravarty S, Manoj A, Li M, Ruben AJ, Li T, Eappen AG, Stafford RE, Natasha KC, Murshedkar T, DeCederfelt H, Plummer SH, Hendel CS, Novik L, Costner PJ, Saunders JG, Laurens MB, Plowe CV, Flynn B, Whalen WR, Todd JP, Noor J, Rao S, Sierra-Davidson K, Lynn GM, Epstein JE, Kemp MA, Fahle GA, Mikolajczak SA, Fishbaugher M, Sack BK, Kappe SH, Davidson SA, Garver LS, Bjorkstrom NK, Nason MC, Graham BS, Roederer M, Sim BK, Hoffman SL, Ledgerwood JE, Seder RA. Protection against malaria at 1 year and immune correlates following PfSPZ vaccination. Nat Med. 2016;22(6):614–23.

    Article  CAS  PubMed  Google Scholar 

  • Kariu T, Ishino T, Yano K, Chinzei Y, Yuda M. CelTOS, a novel malarial protein that mediates transmission to mosquito and vertebrate hosts. Mol Microbiol. 2006;59:1369–79.

    Article  CAS  PubMed  Google Scholar 

  • Kebaier C, Voza T, Vanderberg J. Kinetics of mosquito-injected Plasmodium sporozoites in mice: fewer sporozoites are injected into sporozoite-immunized mice. PLoS Pathog. 2009;5(4):e1000399.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kester KE, Cummings JF, Ofori-Anyinam O, Ockenhouse CF, Krzych U, Moris P, Schwenk R, Nielsen RA, Debebe Z, Pinelis E, Juompan L, Williams J, Dowler M, Stewart VA, Wirtz RA, Dubois MC, Lievens M, Cohen J, Ballou WR, Heppner Jr DG, Rts SVEG. Randomized, double-blind, phase 2a trial of falciparum malaria vaccines RTS,S/AS01B and RTS,S/AS02A in malaria-naive adults: safety, efficacy, and immunologic associates of protection. J Infect Dis. 2009;200(3):337–46.

    Article  CAS  PubMed  Google Scholar 

  • Krzych U, Schwenk J. The dissection of CD8 T cells during liver-stage infection. Curr Top Microbiol Immunol. 2005;297:1–24.

    PubMed  CAS  Google Scholar 

  • Krzych U, Dalai S, Zarling S, Pichugin A. Memory CD8 T cells specific for plasmodia liver-stage antigens maintain protracted protection against malaria. Front Immunol. 2012;3:370.

    Article  PubMed  PubMed Central  Google Scholar 

  • Langhorne J, Ndungu FM, Sponaas AM, Marsh K. Immunity to malaria: more questions than answers. Nat Immunol. 2008;9(7):725–32.

    Article  CAS  PubMed  Google Scholar 

  • Liehl P, Mota MM. Innate recognition of malarial parasites by mammalian hosts. Int J Parasitol. 2012;42(6):557–66.

    Article  CAS  PubMed  Google Scholar 

  • Liehl P, Zuzarte-Luis V, Chan J, Zillinger T, Baptista F, Carapau D, Konert M, Hanson KK, Carret C, Lassnig C, Muller M, Kalinke U, Saeed M, Chora AF, Golenbock DT, Strobl B, Prudencio M, Coelho LP, Kappe SH, Superti-Furga G, Pichlmair A, Vigario AM, Rice CM, Fitzgerald KA, Barchet W, Mota MM. Host-cell sensors for Plasmodium activate innate immunity against liver-stage infection. Nat Med. 2014;20(1):47–53.

    Article  CAS  PubMed  Google Scholar 

  • Limbach K, Aguiar J, Gowda K, Patterson N, Abot E, Sedegah M, Sacci J, Richie T. Identification of two new protective pre-erythrocytic malaria vaccine antigen candidates. Malar J. 2011;10:65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Longley RJ, Salman AM, Cottingham MG, Ewer K, Janse CJ, Khan SM, Spencer AJ, Hill AV. Comparative assessment of vaccine vectors encoding ten malaria antigens identifies two protective liver-stage candidates. Sci Rep. 2015;5:11820.

    Article  PubMed  PubMed Central  Google Scholar 

  • Lumsden JM, Schwenk RJ, Rein LE, Moris P, Janssens M, Ofori-Anyinam O, Cohen J, Kester KE, Heppner DG, Krzych U. Protective immunity induced with the RTS,S/AS vaccine is associated with IL-2 and TNF-alpha producing effector and central memory CD4 T cells. PLoS One. 2011;6(7):e20775.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mac-Daniel L, Buckwalter MR, Berthet M, Virk Y, Yui K, Albert ML, Gueirard P, Menard R. Local immune response to injection of Plasmodium sporozoites into the skin. J Immunol. 2014;193(3):1246–57.

    Article  CAS  PubMed  Google Scholar 

  • Miller JL, Sack BK, Baldwin M, Vaughan AM, Kappe SH. Interferon-mediated innate immune responses against malaria parasite liver stages. Cell Rep. 2014;7(2):436–47.

    Article  CAS  PubMed  Google Scholar 

  • Moncunill G, De Rosa SC, Ayestaran A, Nhabomba AJ, Mpina M, Cohen KW, Jairoce C, Rutishauser T, Campo JJ, Harezlak J, Sanz H, Diez-Padrisa N, Williams NA, Morris D, Aponte JJ, Valim C, Daubenberger C, Dobano C, McElrath MJ. RTS,S/AS01E malaria vaccine induces memory and polyfunctional T cell responses in a pediatric African phase III trial. Front Immunol. 2017;8:1008.

    Article  PubMed  PubMed Central  Google Scholar 

  • Moormann AM, Sumba PO, Tisch DJ, Embury P, King CH, Kazura JW, John CC. Stability of interferon-gamma and interleukin-10 responses to Plasmodium falciparum liver stage antigen 1 and thrombospondin-related adhesive protein immunodominant epitopes in a highland population from Western Kenya. Am J Trop Med Hyg. 2009;81(3):489–95.

    Article  PubMed  PubMed Central  Google Scholar 

  • Morrot A, Rodrigues MM. Tissue signatures influence the activation of intrahepatic CD8(+) T cells against malaria sporozoites. Front Microbiol. 2014;5:440.

    Article  PubMed  PubMed Central  Google Scholar 

  • Morrot A, Zavala F. Effector and memory CD8(+) T cells as seen in immunity to malaria. Immunol Rev. 2004;201:291–303.

    Article  CAS  PubMed  Google Scholar 

  • Mueller AK, Labaied M, Kappe SH, Matuschewski K. Genetically modified Plasmodium parasites as a protective experimental malaria vaccine. Nature. 2005;433(7022):164–7.

    Article  CAS  PubMed  Google Scholar 

  • Pichugin A, Zarling S, Perazzo L, Duffy PE, Ploegh HL, Krzych U. Identification of a Novel CD8 T Cell Epitope Derived from Plasmodium berghei protective Liver-Stage Antigen. Front Immunol. 2018;9:91.

    Article  PubMed  PubMed Central  Google Scholar 

  • Plebanski M, Flanagan KL, Lee EA, Reece WH, Hart K, Gelder C, Gillespie G, Pinder M, Hill AV. Interleukin 10-mediated immunosuppression by a variant CD4 T cell epitope of Plasmodium falciparum. Immunity. 1999;10(6):651–60.

    Article  CAS  PubMed  Google Scholar 

  • Radtke AJ, Tse SW, Zavala F. From the draining lymph node to the liver: the induction and effector mechanisms of malaria-specific CD8+ T cells. Semin Immunopathol. 2015;37(3):211–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rathore D, Sacci JB, de la Vega P, McCutchan TF. Binding and invasion of liver cells by Plasmodium falciparum sporozoites. Essential involvement of the amino terminus of circumsporozoite protein. J Biol Chem. 2002;277:7092–8.

    Article  CAS  PubMed  Google Scholar 

  • Robson KJ, Frevert U, Reckmann I, Cowan G, Beier J, Scragg IG, Takehara K, Bishop DH, Pradel G, Sinden R, et al. Thrombospondin-related adhesive protein (TRAP) of Plasmodium falciparum: expression during sporozoite ontogeny and binding to human hepatocytes. EMBO J. 1995;14(16):3883–94.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Seguin MC, Klotz FW, Schneider I, Weir JP, Goodbary M, Slayter M, Raney JJ, Aniagolu JU, Green SJ. 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. 1994;180(1):353–8.

    Article  CAS  PubMed  Google Scholar 

  • Shin SC, Vanderberg JP, Terzakis JA. Direct infection of hepatocytes by sporozoites of Plasmodium berghei. J Protozool. 1982;29:448–54.

    Article  CAS  PubMed  Google Scholar 

  • Sinnis P, Zavala F. The skin: where malaria infection and the host immune response begin. Semin Immunopathol. 2012;34(6):787–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Speake C, Pichugin A, Sahu T, Malkov V, Morrison R, Pei Y, Juompan L, Milman N, Zarling S, Anderson C, Wong-Madden S, Wendler J, Ishizuka A, MacMillen ZW, Garcia V, Kappe SH, Krzych U, Duffy PE. Identification of novel pre-erythrocytic malaria antigen candidates for combination vaccines with circumsporozoite protein. PLoS One. 2016;11(7):e0159449.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Steers N, Schwenk R, Bacon DJ, Berenzon D, Williams J, Krzych U. The immune status of Kupffer cells profoundly influences their responses to infectious Plasmodium berghei sporozoites. Eur J Immunol. 2005;35(8):2335–46.

    Article  CAS  PubMed  Google Scholar 

  • Todryk SM, Bejon P, Mwangi T, Plebanski M, Urban B, Marsh K, Hill AV, Flanagan KL. Correlation of memory T cell responses against TRAP with protection from clinical malaria, and CD4 CD25 high T cells with susceptibility in Kenyans. PLoS One. 2008;3(4):e2027.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Toure-Balde A, Perlaza BL, Sauzet JP, Ndiaye M, Aribot G, Tall A, Sokhna C, Rogier C, Corradin G, Roussilhon C, Druilhe P. Evidence for multiple B- and T-cell epitopes in Plasmodium falciparum liver-stage antigen 3. Infect Immun. 2009;77(3):1189–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Trimnell A, Takagi A, Gupta M, Richie TL, Kappe SH, Wang R. Genetically attenuated parasite vaccines induce contact-dependent CD8+ T cell killing of Plasmodium yoelii liver stage-infected hepatocytes. J Immunol. 2009;183(9):5870–8.

    Article  CAS  PubMed  Google Scholar 

  • Tsuji M. A retrospective evaluation of the role of T cells in the development of malaria vaccine. Exp Parasitol. 2010;126(3):421–5.

    Article  CAS  PubMed  Google Scholar 

  • Van Braeckel-Budimir N, Harty JT. CD8 T-cell-mediated protection against liver-stage malaria: lessons from a mouse model. Front Microbiol. 2014;5:272.

    PubMed  PubMed Central  Google Scholar 

  • Vaughan AM, Kappe SHI. Genetically attenuated malaria parasites as vaccines. Expert Rev Vaccines. 2017;16(8):765–7.

    Article  CAS  PubMed  Google Scholar 

  • Walk J, Reuling IJ, Behet MC, Meerstein-Kessel L, Graumans W, van Gemert GJ, Siebelink-Stoter R, van de Vegte-Bolmer M, Janssen T, Teelen K, de Wilt JHW, de Mast Q, van der Ven AJ, Diez Benavente E, Campino S, Clark TG, Huynen MA, Hermsen CC, Bijker EM, Scholzen A, Sauerwein RW. Modest heterologous protection after Plasmodium falciparum sporozoite immunization: a double-blind randomized controlled clinical trial. BMC Med. 2017;15(1):168.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

The authors would like to express their thanks to all the members of the Krzych lab for their valuable discussions, Isaac Chalom for the many years of working in the Krzych lab, and Abby London for proofreading the manuscript. The US Army Materiel Command supported this work. The views of the authors do not reflect the position of the Department of the Army or the Department of Defense.

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Krzych, U., Zarling, S., Pichugin, A.V. (2018). Pre-erythrocytic Immunity in Malaria. In: Kremsner, P., Krishna, S. (eds) Encyclopedia of Malaria. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8757-9_137-1

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