Hostname: page-component-78c5997874-xbtfd Total loading time: 0 Render date: 2024-10-30T21:33:24.322Z Has data issue: false hasContentIssue false
  • English
  • Français

Mechanisms of naturally acquired immunity to P. falciparum and approaches to identify merozoite antigen targets

Published online by Cambridge University Press:  16 November 2017

Julie Healer Open the ORCID record for Julie Healer [Opens in a new window] ,
Chris Y. Chiu  and
Diana S. Hansen
Julie Healer*
Affiliation:
The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia
Chris Y. Chiu
Affiliation:
The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia
Diana S. Hansen
Affiliation:
The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia
*
Author for correspondence: Julie Healer, E-mail: healer@wehi.edu.au
Get access Rights & Permissions [Opens in a new window]

Abstract

Malaria is one the most serious infectious diseases with over 200 million clinical cases annually. Most cases of the severe disease are caused by Plasmodium falciparum. The blood stage of Plasmodium parasite is entirely responsible for malaria-associated pathology. The population most susceptible to severe malaria are children under the age of 5, with low levels of immunity. It is only after many years of repeated exposure that individuals living in endemic areas develop clinical immunity. This form of protection prevents clinical episodes by substantially reducing parasite burden. Naturally acquired immunity predominantly targets blood-stage parasites with antibody responses being the main mediators of protection. The targets of clinical immunity are the extracellular merozoite and the infected erythrocyte surface, with the extremely diverse PfEMP1 proteins the main target here. This observation provides a strong rationale that an effective anti-malaria vaccine targeting blood-stage parasites is achievable. Thus the identification of antigenic targets of naturally acquired immunity remains an important step towards the formulation of novel vaccine combinations before testing their efficacy in clinical trials. This review summarizes the main findings to date defining antigenic targets present on the extracellular merozoite associated with naturally acquired immunity to P. falciparum malaria.

Keywords

Antibodiesantigenshumoral immunitymalariamerozoiteP. falciparum
Type
Review Article
Information
Parasitology , Volume 145 , Issue 7 , June 2018 , pp. 839 - 847
Check for updates
Copyright
Copyright © Cambridge University Press 2017 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Agak, GW, Bejon, P, Fegan, G, Gicheru, N, Villard, V, Kajava, AV, Marsh, K and Corradin, G (2008) Longitudinal analyses of immune responses to Plasmodium falciparum derived peptides corresponding to novel blood stage antigens in coastal Kenya. Vaccine 26, 1963–1971.Google Scholar
Ahlborg, N, Iqbal, J, Bjork, L, Stahl, S, Perlmann, P and Berzins, K (1996) Plasmodium falciparum: differential parasite growth inhibition mediated by antibodies to the antigens Pf332 and Pf155/RESA. Experimental Parasitology 82, 155–163.Google Scholar
Amanna, IJ, Carlson, NE and Slifka, MK (2007) Duration of humoral immunity to common viral and vaccine antigens. New England Journal of Medicine 357, 1903–1915.CrossRefGoogle ScholarPubMed
Bai, T, Becker, M, Gupta, A, Strike, P, Murphy, VJ, Anders, RF and Batchelor, AH (2005) Structure of AMA1 from Plasmodium falciparum reveals a clustering of polymorphisms that surround a conserved hydrophobic pocket. Proceedings of the National Academy of Sciences USA 102, 12736–12741.Google Scholar
Baird, JK (1995) Host age as a determinant of naturally acquired immunity to Plasmodium falciparum. Parasitology Today 11, 105–111.Google Scholar
Baird, JK, Jones, TR, Danudirgo, EW, Annis, BA, Bangs, MJ, Basri, H, Purnomo, Masbar, S (1991) Age-dependent acquired protection against Plasmodium falciparum in people having two years exposure to hyperendemic malaria. American Journal of Tropical Medicine and Hygeine 45, 65–76.Google Scholar
Baum, J, Chen, L, Healer, J, Lopaticki, S, Boyle, M, Triglia, T, Ehlgen, F, Ralph, SA, Beeson, JG and Cowman, AF (2009) Reticulocyte-binding protein homologue 5 – an essential adhesin involved in invasion of human erythrocytes by Plasmodium falciparum. International Journal for Parasitology 39, 371–380.Google Scholar
Bergmann-Leitner, ES, Duncan, EH and Angov, E (2009) MSP-1p42-specific antibodies affect growth and development of intra-erythrocytic parasites of Plasmodium falciparum. Malaria Journal 8, 183.Google Scholar
Biggs, BA, Goozé, L, Wycherley, K, Wollish, W, Southwell, B, Leech, JH and Brown, GV (1991) Antigenic variation in Plasmodium falciparum. Proceedings of the National Academy of Sciences USA 88, 9171–9174.CrossRefGoogle ScholarPubMed
Blackman, MJ, Scott-Finnigan, TJ, Shai, S and Holder, AA (1994) Antibodies inhibit the protease-mediated processing of a malaria merozoite surface protein. Journal of Experimental Medicine 180, 389–393.Google Scholar
Bouharoun-Tayoun, H, Oeuvray, C, Lunel, F and Druilhe, P (1995) Mechanisms underlying the monocyte-mediated antibody-dependent killing of Plasmodium falciparum asexual blood stages. Journal of Experimental Medicine 182, 409–418.Google Scholar
Boyle, MJ, Langer, C, Chan, JA, Hodder, AN, Coppel, RL, Anders, RF and Beeson, JG (2014) Sequential processing of merozoite surface proteins during and after erythrocyte invasion by Plasmodium falciparum. Infection & Immunity 82, 924–936.Google Scholar
Boyle, MJ, Reiling, L, Feng, G, Langer, C, Osier, FH, Aspeling-Jones, H, Cheng, YS, Stubbs, J, Tetteh, KK, Conway, DJ, McCarthy, JS, Muller, I, Marsh, K, Anders, RF and Beeson, JG (2015) Human antibodies fix complement to inhibit Plasmodium falciparum invasion of erythrocytes and are associated with protection against malaria. Immunity 42, 580–590.Google Scholar
Bozdech, Z, Llinas, M, Pulliam, BL, Wong, ED, Zhu, J and DeRisi, JL (2003) The transcriptome of the intraerythrocytic developmental cycle of Plasmodium falciparum. PLoS Biology 1, E5.Google Scholar
Cavanagh, DR, Elhassan, IM, Roper, C, Robinson, VJ, Giha, H, Holder, AA, Hviid, L, Theander, TG, Arnot, DE and McBride, JS (1998) A longitudinal study of type-specific antibody responses to Plasmodium falciparum merozoite surface protein-1 in an area of unstable malaria in Sudan. The Journal of Immunology 161, 347–359.Google Scholar
Cavanagh, DR, Dodoo, D, Hviid, L, Kurtzhals, JA, Theander, TG, Akanmori, BD, Polley, S, Conway, DJ, Koram, K and McBride, JS (2004) Antibodies to the N-terminal block 2 of Plasmodium falciparum merozoite surface protein 1 are associated with protection against clinical malaria. Infection & Immunity 72, 6492–6502.Google Scholar
Celada, A, Cruchaud, A and Perrin, LH (1982) Opsonic activity of human immune serum on in vitro phagocytosis of Plasmodium falciparum infected red blood cells by monocytes. Clinical and Experimental Immunology 47, 635–644.Google Scholar
Chen, L, Lopaticki, S, Riglar, DT, Dekiwadia, C, Uboldi, AD, Tham, WH, O'Neill, MT, Richard, D, Baum, J, Ralph, SA and Cowman, AF (2011) An EGF-like protein forms a complex with PfRh5 and is required for invasion of human erythrocytes by Plasmodium falciparum. PLoS Pathogens 7, e1002199.Google Scholar
Chen, L, Xu, Y, Healer, J, Thompson, JK, Smith, BJ, Lawrence, MC and Cowman, AF (2014) Crystal structure of PfRh5, an essential P. falciparum ligand for invasion of human erythrocytes. Elife 3.Google Scholar
Chen, L, Xu, Y, Wong, W, Thompson, JK, Healer, J, Goddard-Borger, ED, Lawrence, MC and Cowman, AF (2017) Structural basis for inhibition of erythrocyte invasion by antibodies to Plasmodium falciparum protein CyRPA. Elife 6.Google Scholar
Chitarra, V, Holm, I, Bentley, GA, Petres, S and Longacre, S (1999) The crystal structure of C-terminal merozoite surface protein 1 at 1·8 A resolution, a highly protective malaria vaccine candidate. Molecular Cell 3, 457–464.Google Scholar
Chiu, CY, Healer, J, Thompson, JK, Chen, L, Kaul, A, Savergave, L, Raghuwanshi, A, Li Wai Suen, CS, Siba, PM, Schofield, L, Mueller, I, Cowman, AF and Hansen, DS (2014) Association of antibodies to Plasmodium falciparum reticulocyte binding protein homolog 5 with protection from clinical malaria. Front Microbiol 5, 314.Google Scholar
Chiu, CY, Hodder, AN, Lin, CS, Hill, DL, Li Wai Suen, CS, Schofield, L, Siba, PM, Mueller, I, Cowman, AF and Hansen, DS (2015) Antibodies to the Plasmodium falciparum proteins MSPDBL1 and MSPDBL2 opsonize merozoites, inhibit parasite growth, and predict protection from clinical Malaria. Journal of Infectious Diseases 212, 406–415.CrossRefGoogle Scholar
Chiu, CY, White, MT, Healer, J, Thompson, JK, Siba, PM, Mueller, I, Cowman, AF and Hansen, DS (2016) Different regions of Plasmodium falciparum erythrocyte-binding antigen 175 induce antibody responses to infection of varied efficacy. Journal of Infectious Diseases 214, 96–104.Google Scholar
Cohen, S and Butcher, GA (1970) Properties of protective malarial antibody. Nature 225, 732–734.Google Scholar
Cohen, S and Butcher, GA (1971) Serum antibody in acquired malarial immunity. Transactions of the Royal Society of Tropical Medicine and Hygeine 65, 125–135.Google Scholar
Cohen, S, McGregor, IA and Carrington, SC (1961) Gamma-globulin and acquired immunity to human malaria. Nature 192, 733–737.Google Scholar
Cohen, S, Butcher, GA and Crandall, RB (1969) Action of malarial antibody in vitro. Nature 223, 368–371.Google Scholar
Cole-Tobian, JL, Michon, P, Biasor, M, Richards, JS, Beeson, JG, Mueller, I and King, CL (2009) Strain-specific duffy binding protein antibodies correlate with protection against infection with homologous compared to heterologous Plasmodium vivax strains in Papua New Guinean children. Infection & Immunity 77, 4009–4017.Google Scholar
Cowman, AF and Crabb, BS (2006) Invasion of red blood cells by malaria parasites. Cell 124, 755–766.Google Scholar
Cowman, AF, Healer, J, Marapana, D and Marsh, K (2016) Malaria: biology and disease. Cell 167, 610–624.Google Scholar
Crompton, PD, Kayala, MA, Traore, B, Kayentao, K, Ongoiba, A, Weiss, GE, Molina, DM, Burk, CR, Waisberg, M, Jasinskas, A, Tan, X, Doumbo, S, Doumtabe, D, Kone, Y, Narum, DL, Liang, X, Doumbo, OK, Miller, LH, Doolan, DL, Baldi, P, Felgner, PL and Pierce, SK (2010 a). A prospective analysis of the Ab response to P lasmodium falciparum before and after a malaria season by protein microarray. Proceedings of the National Academy of Sciences USA 107, 6958–6963.Google Scholar
Crompton, PD, Miura, K, Traore, B, Kayentao, K, Ongoiba, A, Weiss, G, Doumbo, S, Doumtabe, D, Kone, Y, Huang, CY, Doumbo, OK, Miller, LH, Long, CA and Pierce, SK (2010 b). In vitro growth-inhibitory activity and malaria risk in a cohort study in Mali. Infection & Immunity 78, 737–745.CrossRefGoogle Scholar
Crosnier, C, Wanaguru, M, McDade, B, Osier, FH, Marsh, K, Rayner, JC and Wright, GJ (2013) A library of functional recombinant cell-surface and secreted P. falciparum merozoite proteins. Molecular and Cellular Proteomics 12, 3976–3986.Google Scholar
Davies, DH, Liang, X, Hernandez, JE, Randall, A, Hirst, S, Mu, Y, Romero, KM, Nguyen, TT, Kalantari-Dehaghi, M, Crotty, S, Baldi, P, Villarreal, LP and Felgner, PL (2005) Profiling the humoral immune response to infection by using proteome microarrays: high-throughput vaccine and diagnostic antigen discovery. Proceedings of the National Academy of Sciences USA 102, 547–552.Google Scholar
Davies, DH, Duffy, P, Bodmer, JL, Felgner, PL and Doolan, DL (2015) Large screen approaches to identify novel malaria vaccine candidates. Vaccine 33, 7496–7505.CrossRefGoogle ScholarPubMed
Dent, AE, Bergmann-Leitner, ES, Wilson, DW, Tisch, DJ, Kimmel, R, Vulule, J, Sumba, PO, Beeson, JG, Angov, E, Moormann, AM and Kazura, JW (2008) Antibody-mediated growth inhibition of Plasmodium falciparum: relationship to age and protection from parasitemia in Kenyan children and adults. PLoS ONE 3, e3557.CrossRefGoogle ScholarPubMed
Dent, AE, Moormann, AM, Yohn, CT, Kimmel, RJ, Sumba, PO, Vulule, J, Long, CA, Narum, DL, Crabb, BS, Kazura, JW and Tisch, DJ (2012) Broadly reactive antibodies specific for Plasmodium falciparum MSP-1(19) are associated with the protection of naturally exposed children against infection. Malaria Journal 11, 287.Google Scholar
Dent, AE, Nakajima, R, Liang, L, Baum, E, Moormann, AM, Sumba, PO, Vulule, J, Babineau, D, Randall, A, Davies, DH, Felgner, PL and Kazura, JW (2015) Plasmodium falciparum protein microarray antibody profiles correlate with protection from symptomatic Malaria in Kenya. Journal of Infectious Diseases 212, 1429–1438.Google Scholar
Didierlaurent, AM, Laupeze, B, Di Pasquale, A, Hergli, N, Collignon, C and Garcon, N (2017) Adjuvant system AS01: helping to overcome the challenges of modern vaccines. Expert Review of Vaccines 16, 55–63.Google Scholar
Dluzewski, AR, Ling, IT, Hopkins, JM, Grainger, M, Margos, G, Mitchell, GH, Holder, AA and Bannister, LH (2008) Formation of the food vacuole in P lasmodium falciparum: a potential role for the 19 kDa fragment of merozoite surface protein 1 (MSP1(19)). PLoS ONE 3, e3085.Google Scholar
Doolan, DL, Mu, Y, Unal, B, Sundaresh, S, Hirst, S, Valdez, C, Randall, A, Molina, D, Liang, X, Freilich, DA, Oloo, JA, Blair, PL, Aguiar, JC, Baldi, P, Davies, DH and Felgner, PL (2008) Profiling humoral immune responses to P. falciparum infection with protein microarrays. Proteomics 8, 4680–4694.Google Scholar
Douglas, AD, Baldeviano, GC, Lucas, CM, Lugo-Roman, LA, Crosnier, C, Bartholdson, SJ, Diouf, A, Miura, K, Lambert, LE, Ventocilla, JA, Leiva, KP, Milne, KH, Illingworth, JJ, Spencer, AJ, Hjerrild, KA, Alanine, DG, Turner, AV, Moorhead, JT, Edgel, KA, Wu, Y, Long, CA, Wright, GJ, Lescano, AG and Draper, SJ (2015) A PfRH5-based vaccine is efficacious against heterologous strain blood-stage Plasmodium falciparum infection in Aotus monkeys. Cell Host & Microbe 17, 130–139.Google Scholar
Elshal, MF and McCoy, JP (2006) Multiplex bead array assays: performance evaluation and comparison of sensitivity to ELISA. Methods 38, 317–323.CrossRefGoogle ScholarPubMed
Favuzza, P, Guffart, E, Tamborrini, M, Scherer, B, Dreyer, AM, Rufer, AC, Erny, J, Hoernschemeyer, J, Thoma, R, Schmid, G, Gsell, B, Lamelas, A, Benz, J, Joseph, C, Matile, H, Pluschke, G and Rudolph, MG (2017) Structure of the malaria vaccine candidate antigen CyRPA and its complex with a parasite invasion inhibitory antibody. Elife 6.Google Scholar
Florens, L., Washburn, MP, Raine, JD, Anthony, RM, Grainger, M, Haynes, JD, Moch, JK, Muster, N, Sacci, JB, Tabb, DL, Witney, AA, Wolters, D, Wu, Y, Gardner, MJ, Holder, AA, Sinden, RE, Yates, JR and Carucci, DJ (2002) A proteomic view of the Plasmodium falciparum life cycle. Nature 419, 520–526.Google Scholar
Fowkes, FJ, Richards, JS, Simpson, JA and Beeson, JG (2010) The relationship between anti-merozoite antibodies and incidence of Plasmodium falciparum malaria: a systematic review and meta-analysis. PLoS Medicine 7, e1000218.Google Scholar
Fried, M, Nosten, F, Brockman, A, Brabin, BJ and Duffy, PE (1998) Maternal antibodies block malaria. Nature 395, 851–852.Google Scholar
Gardner, MJ, Hall, N, Fung, E, White, O, Berriman, M, Hyman, RW, Carlton, JM, Pain, A, Nelson, KE, Bowman, S, Paulsen, IT, James, K, Eisen, JA, Rutherford, K, Salzberg, SL, Craig, A, Kyes, S, Chan, MS, Nene, V, Shallom, SJ, Suh, B, Peterson, J, Angiuoli, S, Pertea, M, Allen, J, Selengut, J, Haft, D, Mather, MW, Vaidya, AB, Martin, DM, Fairlamb, AH, Fraunholz, MJ, Roos, DS, Ralph, SA, McFadden, GI, Cummings, LM, Subramanian, GM, Mungall, C, Venter, JC, Carucci, DJ, Hoffman, SL, Newbold, C, Davis, RW, Fraser, CM and Barrell, B (2002) Genome sequence of the human malaria parasite Plasmodium falciparum. Nature 419, 498–511.Google Scholar
Gilson, PR, Nebl, T, Vukcevic, D, Moritz, RL, Sargeant, T, Speed, TP, Schofield, L and Crabb, BS (2006) Identification and stoichiometry of glycosylphosphatidylinositol-anchored membrane proteins of the human malaria parasite Plasmodium falciparum. Molecular and Cellular Proteomics 5, 1286–1299.Google Scholar
Gilson, PR, O'Donnell, RA, Nebl, T, Sanders, PR, Wickham, ME, McElwain, TF, de Koning-Ward, TF and Crabb, BS (2008) MSP1(19) miniproteins can serve as targets for invasion inhibitory antibodies in Plasmodium falciparum provided they contain the correct domains for cell surface trafficking. Molecular Microbiology 68, 124–138.Google Scholar
Gomez-Escobar, N, Amambua-Ngwa, A, Walther, M, Okebe, J, Ebonyi, A and Conway, DJ (2010) Erythrocyte invasion and merozoite ligand gene expression in severe and mild Plasmodium falciparum malaria. Journal of Infectious Diseases 201, 444–452.Google Scholar
Green, TJ, Morhardt, M, Brackett, RG and Jacobs, RL (1981) Serum inhibition of merozoite dispersal from Plasmodium falciparum schizonts: indicator of immune status. Infection & Immunity 31, 1203–1208.Google Scholar
Gupta, S, Snow, RW, Donnelly, CA, Marsh, K and Newbold, C (1999) Immunity to non-cerebral severe malaria is acquired after one or two infections. Natural Medicines 5, 340–343.Google Scholar
Hammarlund, E, Lewis, MW, Hansen, SG, Strelow, LI, Nelson, JA, Sexton, GJ, Hanifin, JM and Slifka, MK (2003) Duration of antiviral immunity after smallpox vaccination. Natural Medicines 9, 1131–1137.Google Scholar
Hansen, DS, Obeng-Adjei, N, Ly, A, Ioannidis, LJ and Crompton, PD (2017) Emerging concepts in T follicular helper cell responses to malaria. International Journal for Parasitology 47, 105–110.Google Scholar
Hill, DL, Eriksson, EM, Carmagnac, AB, Wilson, DW, Cowman, AF, Hansen, DS and Schofield, L (2012) Efficient measurement of opsonising antibodies to Plasmodium falciparum merozoites. PLoS ONE 7, e51692.Google Scholar
Hill, DL, Eriksson, EM, Li Wai Suen, CS, Chiu, CY, Ryg-Cornejo, V, Robinson, LJ, Siba, PM, Mueller, I, Hansen, DS and Schofield, L (2013) Opsonising antibodies to P. falciparum merozoites associated with immunity to clinical malaria. PLoS ONE 8, e74627.Google Scholar
Hodder, AN, Crewther, PE and Anders, RF (2001) Specificity of the protective antibody response to apical membrane antigen 1. Infection & Immunity 69, 3286–3294.Google Scholar
Jensen, JB, Boland, MT and Akood, M (1982) Induction of crisis forms in cultured Plasmodium falciparum with human immune serum from Sudan. Science 216, 1230–1233.Google Scholar
Joergensen, LM, Salanti, A, Dobrilovic, T, Barfod, L, Hassenkam, T, Theander, TG, Hviid, L and Arnot, DE (2010) The kinetics of antibody binding to Plasmodium falciparum VAR2CSA PfEMP1 antigen and modelling of PfEMP1 antigen packing on the membrane knobs. Malaria Journal 9, 100.Google Scholar
Joos, C, Marrama, L, Polson, HE, Corre, S, Diatta, AM, Diouf, B, Trape, JF, Tall, A, Longacre, S and Perraut, R (2010) Clinical protection from falciparum malaria correlates with neutrophil respiratory bursts induced by merozoites opsonized with human serum antibodies. PLoS ONE 5, e9871.Google Scholar
Kapelski, S, Klockenbring, T, Fischer, R, Barth, S and Fendel, R (2014) Assessment of the neutrophilic antibody-dependent respiratory burst (ADRB) response to Plasmodium falciparum. Journal of Leukocyte Biology 96, 1131–1142.Google Scholar
Kauth, CW, Woehlbier, U, Kern, M, Mekonnen, Z, Lutz, R, Mucke, N, Langowski, J and Bujard, H (2006) Interactions between merozoite surface proteins 1, 6, and 7 of the malaria parasite Plasmodium falciparum. Journal of Biological Chemistry 281, 31517–31527.Google Scholar
Kennedy, AT, Schmidt, CQ, Thompson, JK, Weiss, GE, Taechalertpaisarn, T, Gilson, PR, Barlow, PN, Crabb, BS, Cowman, AF and Tham, WH (2016) Recruitment of factor H as a novel complement evasion strategy for blood-stage Plasmodium falciparum infection. The Journal of Immunology 196, 1239–1248.Google Scholar
Khusmith, S, Druilhe, P and Gentilini, M (1982) Enhanced Plasmodium falciparum merozoite phagocytosis by monocytes from immune individuals. Infection & Immunity 35, 874–879.Google Scholar
Kinyanjui, SM, Bull, P, Newbold, CI and Marsh, K (2003) Kinetics of antibody responses to Plasmodium falciparum-infected erythrocyte variant surface antigens. Journal of Infectious Diseases 187, 667–674.Google Scholar
Kinyanjui, SM, Conway, DJ, Lanar, DE and Marsh, K (2007) Igg antibody responses to Plasmodium falciparum merozoite antigens in Kenyan children have a short half-life. Malaria Journal 6, 82.Google Scholar
Le Roch, KG, Zhou, Y, Blair, PL, Grainger, M, Moch, JK, Haynes, JD, De La Vega, P, Holder, AA, Batalov, S, Carucci, DJ and Winzeler, EA (2003) Discovery of gene function by expression profiling of the malaria parasite life cycle. Science 301, 1503–1508.Google Scholar
Lin, CS, Uboldi, AD, Marapana, D, Czabotar, PE, Epp, C, Bujard, H, Taylor, NL, Perugini, MA, Hodder, AN and Cowman, AF (2014) The merozoite surface protein 1 complex is a platform for binding to human erythrocytes by Plasmodium falciparum. Journal of Biological Chemistry 289, 25655–25669.Google Scholar
Lin, CS, Uboldi, AD, Epp, C, Bujard, H, Tsuboi, T, Czabotar, PE and Cowman, AF (2016) Multiple Plasmodium falciparum merozoite surface protein 1 complexes mediate merozoite binding to human erythrocytes. Journal of Biological Chemistry 291, 7703–7715.Google Scholar
Lin, DH, Malpede, BM, Batchelor, JD and Tolia, NH (2012) Crystal and solution structures of Plasmodium falciparum erythrocyte-binding antigen 140 reveal determinants of receptor specificity during erythrocyte invasion. Journal of Biological Chemistry 287, 36830–36836.Google Scholar
Llewellyn, D, Miura, K, Fay, MP, Williams, AR, Murungi, LM, Shi, J, Hodgson, SH, Douglas, AD, Osier, FH, Fairhurst, RM, Diakite, M, Pleass, RJ, Long, CA and Draper, SJ (2015) Standardization of the antibody-dependent respiratory burst assay with human neutrophils and Plasmodium falciparum malaria. Scientific Reports 5, 14081.Google Scholar
Lyon, JA, Thomas, AW, Hall, T and Chulay, JD (1989) Specificities of antibodies that inhibit merozoite dispersal from malaria-infected erythrocytes. Molecular and Biochemical Parasitology 36, 77–86.Google Scholar
Maple, PA, Jones, CS, Wall, EC, Vyseb, A, Edmunds, WJ, Andrews, NJ and Miller, E (2000) Immunity to diphtheria and tetanus in England and Wales. Vaccine 19, 167–173.Google Scholar
Marsh, K and Kinyanjui, S (2006) Immune effector mechanisms in malaria. Parasite Immunology 28, 51–60.Google Scholar
McCarra, MB, Ayodo, G, Sumba, PO, Kazura, JW, Moormann, AM, Narum, DL and John, CC (2011) Antibodies to Plasmodium falciparum erythrocyte-binding antigen-175 are associated with protection from clinical malaria. Pediatric Infectious Disease Journal 30, 1037–1042.Google Scholar
McGregor, IA (1964) The passive transfer of human malarial immunity. American Journal of Tropical Medicine and Hygeine 13, 237–239.Google Scholar
Miura, K, Zhou, H, Moretz, SE, Diouf, A, Thera, MA, Dolo, A, Doumbo, O, Malkin, E, Diemert, D, Miller, LH, Mullen, GE and Long, CA (2008) Comparison of biological activity of human anti-apical membrane antigen-1 antibodies induced by natural infection and vaccination. The Journal of Immunology 181, 8776–8783.Google Scholar
Mugyenyi, CK, Elliott, SR, McCallum, FJ, Anders, RF, Marsh, K and Beeson, JG (2013) Antibodies to polymorphic invasion-inhibitory and non-inhibitory epitopes of Plasmodium falciparum apical membrane antigen 1 in human malaria. PLoS ONE 8, e68304.Google Scholar
Murungi, LM, Sonden, K, Llewellyn, D, Rono, J, Guleid, F, Williams, AR, Ogada, E, Thairu, A, Farnert, A, Marsh, K, Draper, SJ and Osier, FH (2016) Targets and mechanisms associated with protection from severe Plasmodium falciparum Malaria in Kenyan children. Infection & Immunity 84, 950–963.Google Scholar
Newman, SL and Mikus, LK (1985) Deposition of C3b and iC3b onto particulate activators of the human complement system. Quantitation with monoclonal antibodies to human C3. Journal of Biological Chemistry 161, 1414–1431.Google Scholar
Obeng-Adjei, N, Portugal, S, Tran, TM, Yazew, TB, Skinner, J, Li, S, Jain, A, Felgner, PL, Doumbo, OK, Kayentao, K, Ongoiba, A, Traore, B and Crompton, PD (2015) Circulating Th1-cell-type Tfh cells that exhibit impaired B cell help are preferentially activated during acute malaria in children. Cell Reports 13, 425–439.Google Scholar
Ogutu, BR, Apollo, OJ, McKinney, D, Okoth, W, Siangla, J, Dubovsky, F, Tucker, K, Waitumbi, JN, Diggs, C, Wittes, J, Malkin, E, Leach, A, Soisson, LA, Milman, JB, Otieno, L, Holland, CA, Polhemus, M, Remich, SA, Ockenhouse, CF, Cohen, J, Ballou, WR, Martin, SK, Angov, E, Stewart, VA, Lyon, JA, Heppner, DG and Withers, MR (2009) Blood stage malaria vaccine eliciting high antigen-specific antibody concentrations confers no protection to young children in Western Kenya. PLoS ONE 4, e4708.Google Scholar
Okell, LC, Ghani, AC, Lyons, E and Drakeley, CJ (2009) Submicroscopic infection in Plasmodium falciparum-endemic populations: a systematic review and meta-analysis. Journal of Infectious Diseases 200, 1509–1517.Google Scholar
Osier, FH, Feng, G, Boyle, MJ, Langer, C, Zhou, J, Richards, JS, McCallum, FJ, Reiling, L, Jaworowski, A, Anders, RF, Marsh, K and Beeson, JG (2014 a). Opsonic phagocytosis of Plasmodium falciparum merozoites: mechanism in human immunity and a correlate of protection against malaria. BMC Medicine 12, 108.Google Scholar
Osier, FH, Mackinnon, MJ, Crosnier, C, Fegan, G, Kamuyu, G, Wanaguru, M, Ogada, E, McDade, B, Rayner, JC, Wright, GJ and Marsh, K (2014 b). New antigens for a multicomponent blood-stage malaria vaccine. Science Translation Medicine 6, 247ra102.Google Scholar
Pang, XL, Mitamura, T and Horii, T (1999) Antibodies reactive with the N-terminal domain of Plasmodium falciparum serine repeat antigen inhibit cell proliferation by agglutinating merozoites and schizonts. Infection & Immunity 67, 1821–1827.Google Scholar
Persson, KE, Lee, CT, Marsh, K and Beeson, JG (2006) Development and optimization of high-throughput methods to measure Plasmodium falciparum-specific growth inhibitory antibodies. Journal of Clinical Microbiology 44, 1665–1673.Google Scholar
Pizarro, JC, Vulliez-Le Normand, B, Chesne-Seck, ML, Collins, CR, Withers-Martinez, C, Hackett, F, Blackman, MJ, Faber, BW, Remarque, EJ, Kocken, CH, Thomas, AW and Bentley, GA (2005) Crystal structure of the malaria vaccine candidate apical membrane antigen 1. Science 308, 408–411.Google Scholar
Pouvelle, B and Gysin, J (1997) Presence of the parasitophorous duct in Plasmodium falciparum and P. vivax parasitized Saimiri monkey red blood cells. Parasitology Today 13, 357–361.Google Scholar
Raj, DK, Nixon, CP, Nixon, CE, Dvorin, JD, DiPetrillo, CG, Pond-Tor, S, Wu, HW, Jolly, G, Pischel, L, Lu, A, Michelow, IC, Cheng, L, Conteh, S, McDonald, EA, Absalon, S, Holte, SE, Friedman, JF, Fried, M, Duffy, PE and Kurtis, JD (2014) Antibodies to PfSEA-1 block parasite egress from RBCs and protect against malaria infection. Science 344, 871–877.Google Scholar
Ramasamy, R, Yasawardena, S, Kanagaratnam, R, Buratti, E, Baralle, FE and Ramasamy, MS (1999) Antibodies to a merozoite surface protein promote multiple invasion of red blood cells by malaria parasites. Parasite Immunology 21, 397–407.Google Scholar
Reddy, KS, Amlabu, E, Pandey, AK, Mitra, P, Chauhan, VS and Gaur, D (2015) Multiprotein complex between the GPI-anchored CyRPA with PfRH5 and PfRipr is crucial for Plasmodium falciparum erythrocyte invasion. Proceedings of the National Academy of Sciences USA 112, 1179–1184.Google Scholar
Reiling, L, Richards, JS, Fowkes, FJ, Barry, AE, Triglia, T, Chokejindachai, W, Michon, P, Tavul, L, Siba, PM, Cowman, AF, Mueller, I and Beeson, JG (2010) Evidence that the erythrocyte invasion ligand PfRh2 is a target of protective immunity against Plasmodium falciparum malaria. The Journal of Immunology 185, 6157–6167.Google Scholar
Reiling, L, Richards, JS, Fowkes, FJ, Wilson, DW, Chokejindachai, W, Barry, AE, Tham, WH, Stubbs, J, Langer, C, Donelson, J, Michon, P, Tavul, L, Crabb, BS, Siba, PM, Cowman, AF, Mueller, I and Beeson, JG (2012) The Plasmodium falciparum erythrocyte invasion ligand Pfrh4 as a target of functional and protective human antibodies against malaria. PLoS ONE 7, e45253.Google Scholar
Richards, JS, Stanisic, DI, Fowkes, FJ, Tavul, L, Dabod, E, Thompson, JK, Kumar, S, Chitnis, CE, Narum, DL, Michon, P, Siba, PM, Cowman, AF, Mueller, I and Beeson, JG (2010) Association between naturally acquired antibodies to erythrocyte-binding antigens of Plasmodium falciparum and protection from malaria and high-density parasitemia. Clinical Infectious Diseases 51, e50–e60.Google Scholar
Richards, JS, Arumugam, TU, Reiling, L, Healer, J, Hodder, AN, Fowkes, FJ, Cross, N, Langer, C, Takeo, S, Uboldi, AD, Thompson, JK, Gilson, PR, Coppel, RL, Siba, PM, King, CL, Torii, M, Chitnis, CE, Narum, DL, Mueller, I, Crabb, BS, Cowman, AF, Tsuboi, T and Beeson, JG (2013) Identification and prioritization of merozoite antigens as targets of protective human immunity to Plasmodium falciparum malaria for vaccine and biomarker development. The Journal of Immunology 191, 795–809.Google Scholar
Roberts, DJ, Craig, AG, Berendt, AR, Pinches, R, Nash, G, Marsh, G and Newbold, CI (1992) Rapid switching to multiple antigenic and adhesive phenotypes in malaria. Nature 357, 689–692.Google Scholar
Ryg-Cornejo, V, Ioannidis, LJ, Ly, A, Chiu, CY, Tellier, J, Hill, DL, Preston, SP, Pellegrini, M, Yu, D, Nutt, SL, Kallies, A and Hansen, DS (2016 a). Severe Malaria infections impair germinal center responses by inhibiting T follicular helper cell differentiation. Cell Reports 14, 68–81.Google Scholar
Ryg-Cornejo, V, Ly, A and Hansen, DS (2016 b). Immunological processes underlying the slow acquisition of humoral immunity to malaria. Parasitology 143, 199–207.Google Scholar
Salanti, A, Dahlback, M, Turner, L, Nielsen, MA, Barfod, L, Magistrado, P, Jensen, AT, Lavstsen, T, Ofori, MF, Marsh, K, Hviid, L and Theander, TG (2004) Evidence for the involvement of VAR2CSA in pregnancy-associated malaria. Journal of Experimental Medicine 200, 1197–1203.Google Scholar
Scherf, A, Lopez-Rubio, JJ and Riviere, L (2008) Antigenic variation in Plasmodium falciparum. Annual Reviews of Microbiology 62, 445–470.Google Scholar
Schofield, L and Grau, GE (2005) Immunological processes in malaria pathogenesis. Nature Reviews Immunology 5, 722–735.Google Scholar
Schofield, L and Mueller, I (2006) Clinical immunity to malaria. Current Molecular Medicine 6, 205–221.Google Scholar
Silver, KL, Higgins, SJ, McDonald, CR and Kain, KC (2010) Complement driven innate immune response to malaria: fuelling severe malarial diseases. Cellular Microbiology 12, 1036–1045.Google Scholar
Simon, N, Lasonder, E, Scheuermayer, M, Kuehn, A, Tews, S, Fischer, R, Zipfel, PF, Skerka, C and Pradel, G (2013) Malaria parasites co-opt human factor H to prevent complement-mediated lysis in the mosquito midgut. Cell Host & Microbe 13, 29–41.Google Scholar
Srinivasan, P, Beatty, WL, Diouf, A, Herrera, R, Ambroggio, X, Moch, JK, Tyler, JS, Narum, DL, Pierce, SK, Boothroyd, JC, Haynes, JD and Miller, LH (2011) Binding of Plasmodium merozoite proteins RON2 and AMA1 triggers commitment to invasion. Proceedings of the National Academy of Sciences USA 108, 13275–13280.Google Scholar
Stanisic, DI and Good, MF (2016) Examining cellular immune responses to inform development of a blood-stage malaria vaccine. Parasitology 143, 208–223.Google Scholar
Stanisic, DI, Richards, JS, McCallum, FJ, Michon, P, King, CL, Schoepflin, S, Gilson, PR, Murphy, VJ, Anders, RF, Mueller, I and Beeson, JG (2009) Immunoglobulin G subclass-specific responses against Plasmodium falciparum merozoite antigens are associated with control of parasitemia and protection from symptomatic illness. Infection & Immunity 77, 1165–1174.Google Scholar
Sun, T and Chakrabarti, C (1985) Schizonts, merozoites, and phagocytosis in falciparum malaria. Annals of Clinical and Laboratory Science 15, 465–469.Google Scholar
Tham, WH, Healer, J and Cowman, AF (2012) Erythrocyte and reticulocyte binding-like proteins of Plasmodium falciparum. Trends in Parasitology 28, 23–30.Google Scholar
Tiendrebeogo, RW, Adu, B, Singh, SK, Dziegiel, MH, Nebie, I, Sirima, SB, Christiansen, M, Dodoo, D and Theisen, M (2015) Antibody-dependent cellular inhibition is associated with reduced risk against febrile Malaria in a longitudinal cohort study involving Ghanaian children. Open Forum Infectious Diseases 2, ofv044.Google Scholar
Tolia, NH, Enemark, EJ, Sim, BK and Joshua-Tor, L (2005) Structural basis for the EBA-175 erythrocyte invasion pathway of the malaria parasite Plasmodium falciparum. Cell 122, 183–193.Google Scholar
Tran, TM, Ongoiba, A, Coursen, J, Crosnier, C, Diouf, A, Huang, CY, Li, S, Doumbo, S, Doumtabe, D, Kone, Y, Bathily, A, Dia, S, Niangaly, M, Dara, C, Sangala, J, Miller, LH, Doumbo, OK, Kayentao, K, Long, CA, Miura, K, Wright, GJ, Traore, B and Crompton, PD (2014) Naturally acquired antibodies specific for Plasmodium falciparum reticulocyte-binding protein homologue 5 inhibit parasite growth and predict protection from malaria. Journal of Infectious Diseases 209, 789–798.Google Scholar
Tsuboi, T, Takeo, S, Arumugam, TU, Otsuki, H and Torii, M (2010) The wheat germ cell-free protein synthesis system: a key tool for novel malaria vaccine candidate discovery. Acta Tropica 114, 171–176.Google Scholar
Turrini, F, Ginsburg, H, Bussolino, F, Pescarmona, GP, Serra, MV and Arese, P (1992) Phagocytosis of Plasmodium falciparum-infected human red blood cells by human monocytes: involvement of immune and nonimmune determinants and dependence on parasite developmental stage. Blood 80, 801–808.Google Scholar
Volz, JC, Yap, A, Sisquella, X, Thompson, JK, Lim, NT, Whitehead, LW, Chen, L, Lampe, M, Tham, WH, Wilson, D, Nebl, T, Marapana, D, Triglia, T, Wong, W, Rogers, KL and Cowman, AF (2016) Essential role of the PfRh5/PfRipr/CyRPA complex during Plasmodium falciparum invasion of erythrocytes. Cell Host & Microbe 20, 60–71.Google Scholar
Weiss, GE, Traore, B, Kayentao, K, Ongoiba, A, Doumbo, S, Doumtabe, D, Kone, Y, Dia, S, Guindo, A, Traore, A, Huang, CY, Miura, K, Mircetic, M, Li, S, Baughman, A, Narum, DL, Miller, LH, Doumbo, OK, Pierce, SK and Crompton, PD (2010) The Plasmodium falciparum-specific human memory B cell compartment expands gradually with repeated malaria infections. PLoS Pathogens 6, e1000912.Google Scholar
Weiss, GE, Crabb, BS and Gilson, PR (2016) Overlaying molecular and temporal aspects of malaria parasite invasion. Trends in Parasitology 32, 284–295.Google Scholar
Wilson, DW, Fowkes, FJ, Gilson, PR, Elliott, SR, Tavul, L, Michon, P, Dabod, E, Siba, PM, Mueller, I, Crabb, BS and Beeson, JG (2011) Quantifying the importance of MSP1-19 as a target of growth-inhibitory and protective antibodies against Plasmodium falciparum in humans. PLoS ONE 6, e27705.Google Scholar
Wipasa, J, Suphavilai, C, Okell, LC, Cook, J, Corran, PH, Thaikla, K, Liewsaree, W, Riley, EM and Hafalla, JC (2010) Long-lived antibody and B cell memory responses to the human malaria parasites, Plasmodium falciparum and Plasmodium vivax. PLoS Pathogens 6, e1000770.Google Scholar
Witko-Sarsat, V, Rieu, P, Descamps-Latscha, B, Lesavre, P and Halbwachs-Mecarelli, L (2000) Neutrophils: molecules, functions and pathophysiological aspects. Laboratory Investigation 80, 617–653.Google Scholar
World Health Organization (2016) World Malaria report 2016.Google Scholar
Wright, KE, Hjerrild, KA, Bartlett, J, Douglas, AD, Jin, J, Brown, RE, Illingworth, JJ, Ashfield, R, Clemmensen, SB, de Jongh, WA, Draper, SJ and Higgins, MK (2014) Structure of malaria invasion protein RH5 with erythrocyte basigin and blocking antibodies. Nature 515, 427–430.Google Scholar