Subunit Blood-Stage Malaria Vaccines
Abstract
The existence of asymptomatically parasitemic individuals in malaria-endemic areas has long been recognised to signify naturally acquired immunity to malaria disease, resulting from control of the parasite’s asexual blood-stage. This has for many years been viewed as a ‘proof-of-concept’ encouraging the development of blood-stage vaccines (BSVs). Results of clinical trials of candidate subunit BSVs have mostly, however, not lived up to early expectations and the field is currently experiencing a challenging period.
This chapter examines the current state of BSV development and prospects for developments in the near future. The various immunological mechanisms by which BSVs might conceivably induce protection are examined, along with the means of assaying these effectors in vitro. Pre-clinical and clinical in vivo models are discussed, particularly highlighting the potential value of the blood-stage controlled human malaria infection (CHMI) model. A summary of the results of clinical trials over the last 25 years is provided, along with an overview of trials currently under way. Consistent with their prominence in the field’s efforts, vaccines targeting the Plasmodium falciparum merozoite are the main focus, but vaccines against Plasmodium vivax and PfEMP1 (including pregnancy-associated malaria) are also discussed. Finally, a personal view of possible areas for future development is presented.
Keywords
Asexual blood-stage Malaria Plasmodium falciparum Plasmodium vivax Subunit vaccine Candidate prioritisation Review of clinical trials Pregnancy-associated malariaSupplementary material
References
- 1.Langhorne J, Ndungu FM, Sponaas AM, Marsh K (2008) Immunity to malaria: more questions than answers. Nat Immunol 9:725–732PubMedCrossRefGoogle Scholar
- 2.Riley EM, Stewart VA (2013) Immune mechanisms in malaria: new insights in vaccine development. Nat Med 19:168–178PubMedCrossRefGoogle Scholar
- 3.Cohen S, McGregor IA, Carrington S (1961) Gamma-globulin and acquired immunity to human malaria. Nature 192:733–737PubMedCrossRefGoogle Scholar
- 4.Sabchareon A, Burnouf T, Ouattara D, Attanath P, Bouharountayoun H, Chantavanich P, Foucault C, Chongsuphajaisiddhi T, Druilhe P (1991) Parasitological and clinical human response to immunoglobulin administration in falciparum malaria. Am J Trop Med Hyg 45:297–308PubMedGoogle Scholar
- 5.Bejon P, White MT, Olotu A, Bojang K, Lusingu JP, Salim N, Otsyula NN, Agnandji ST, Asante KP, Owusu-Agyei S et al (2013) Efficacy of RTS, S malaria vaccines: individual-participant pooled analysis of phase 2 data. Lancet Infect Dis 13:319–327PubMedPubMedCentralCrossRefGoogle Scholar
- 6.Pemberton-Ross P, Smith TA, Hodel EM, Kay K, Penny MA (2015) Age-shifting in malaria incidence as a result of induced immunological deficit: a simulation study. Malar J 14:287PubMedPubMedCentralCrossRefGoogle Scholar
- 7.Draper SJ, Angov E, Horii T, Miller LH, Srinivasan P, Theisen M, Biswas S (2015) Recent advances in recombinant protein-based malaria vaccines. Vaccine 33(52):7433–7443PubMedPubMedCentralCrossRefGoogle Scholar
- 8.Udomsangpetch R, Kaneko O, Chotivanich K, Sattabongkot J (2008) Cultivation of Plasmodium vivax. Trends Parasitol 24:85–88PubMedCrossRefGoogle Scholar
- 9.Bull PC, Abdi AI (2016) The role of PfEMP1 as targets of naturally acquired immunity to childhood malaria: prospects for a vaccine. Parasitology 143:171–186PubMedPubMedCentralCrossRefGoogle Scholar
- 10.Deans JA, Alderson T, Thomas AW, Mitchell GH, Lennox ES, Cohen S (1982) Rat monoclonal antibodies which inhibit the in vitro multiplication of Plasmodium knowlesi. Clin Exp Immunol 49:297–309PubMedPubMedCentralGoogle Scholar
- 11.Freeman RR, Trejdosiewicz AJ, Cross GA (1980) Protective monoclonal antibodies recognising stage-specific merozoite antigens of a rodent malaria parasite. Nature 284:366–368PubMedCrossRefGoogle Scholar
- 12.Holder AA, Freeman RR (1981) Immunization against blood-stage rodent malaria using purified parasite antigens. Nature 294:361–364PubMedCrossRefGoogle Scholar
- 13.Dvorak JA, Miller LH, Whitehouse WC, Shiroishi T (1975) Invasion of erythrocytes by malaria merozoites. Science 187:748–750PubMedCrossRefGoogle Scholar
- 14.Gilson PR, Crabb BS (2009) Morphology and kinetics of the three distinct phases of red blood cell invasion by Plasmodium falciparum merozoites. Int J Parasitol 39:91–96PubMedCrossRefGoogle Scholar
- 15.Saul A (1987) Kinetic constraints on the development of a malaria vaccine. Parasite Immunol 9:1–9PubMedCrossRefGoogle Scholar
- 16.Douglas AD, Williams AR, Knuepfer E, Illingworth JJ, Furze JM, Crosnier C, Choudhary P, Bustamante LY, Zakutansky SE, Awuah DK et al (2014) Neutralization of Plasmodium falciparum merozoites by antibodies against PfRH5. J Immunol 192:245–258PubMedCrossRefGoogle Scholar
- 17.Dutta S, Dlugosz LS, Drew DR, Ge X, Ababacar D, Rovira YI, Moch JK, Shi M, Long CA, Foley M et al (2013) Overcoming antigenic diversity by enhancing the immunogenicity of conserved epitopes on the malaria vaccine candidate apical membrane antigen-1. PLoS Pathog 9, e1003840PubMedPubMedCentralCrossRefGoogle Scholar
- 18.Miura K, Zhou H, Diouf A, Moretz SE, Fay MP, Miller LH, Martin LB, Pierce MA, Ellis RD, Mullen GE et al (2009) Anti-apical-membrane-antigen-1 antibody is more effective than anti-42-kilodalton-merozoite-surface-protein-1 antibody in inhibiting Plasmodium falciparum growth, as determined by the in vitro growth inhibition assay. Clin Vaccine Immunol 16:963–968PubMedPubMedCentralCrossRefGoogle Scholar
- 19.Williams AR, Douglas AD, Miura K, Illingworth JJ, Choudhary P, Murungi LM, Furze JM, Diouf A, Miotto O, Crosnier C et al (2012) Enhancing blockade of Plasmodium falciparum erythrocyte invasion: assessing combinations of antibodies against PfRH5 and other merozoite antigens. PLoS Pathog 8, e1002991PubMedPubMedCentralCrossRefGoogle Scholar
- 20.Douglas AD, Baldeviano GC, Lucas CM, Lugo-Roman LA, Crosnier C, Bartholdson SJ, Diouf A, Miura K, Lambert LE, Ventocilla JA et al (2015) A PfRH5-based vaccine is efficacious against heterologous strain blood-stage Plasmodium falciparum infection in Aotus monkeys. Cell Host Microbe 17:130–139PubMedPubMedCentralCrossRefGoogle Scholar
- 21.Payne RO, Milne KH, Elias SC, Edwards NJ, Douglas AD, Brown RE, Silk SE, Biswas S, Miura K, Roberts R et al (2016) Demonstration of the blood-stage controlled human malaria infection model to assess efficacy of the Plasmodium falciparum AMA1 vaccine FMP2.1/AS01. J Infect Dis 213(11):1743–1751PubMedCrossRefGoogle Scholar
- 22.Graves P, Gelband H (2006) Vaccines for preventing malaria (SPf66). Cochrane Database Syst Rev CD005966Google Scholar
- 23.Genton B, Betuela I, Felger I, Al-Yaman F, Anders RF, Saul A, Rare L, Baisor M, Lorry K, Brown GV et al (2002) A recombinant blood-stage malaria vaccine reduces Plasmodium falciparum density and exerts selective pressure on parasite populations in a phase 1-2b trial in Papua New Guinea. J Infect Dis 185:820–827PubMedCrossRefGoogle Scholar
- 24.Thera MA, Doumbo OK, Coulibaly D, Laurens MB, Ouattara A, Kone AK, Guindo AB, Traore K, Traore I, Kouriba B et al (2011) A field trial to assess a blood-stage malaria vaccine. N Engl J Med 365:1004–1013PubMedPubMedCentralCrossRefGoogle Scholar
- 25.Spring MD, Cummings JF, Ockenhouse CF, Dutta S, Reidler R, Angov E, Bergmann-Leitner E, Stewart VA, Bittner S, Juompan L et al (2009) Phase 1/2a study of the malaria vaccine candidate apical membrane antigen-1 (AMA-1) administered in adjuvant system AS01B or AS02A. PLoS One 4, e5254PubMedPubMedCentralCrossRefGoogle Scholar
- 26.Sirima SB, Cousens S, Druilhe P (2011) Protection against malaria by MSP3 candidate vaccine. N Engl J Med 365:1062–1064PubMedCrossRefGoogle Scholar
- 27.Palacpac NM, Ntege E, Yeka A, Balikagala B, Suzuki N, Shirai H, Yagi M, Ito K, Fukushima W, Hirota Y et al (2013) Phase 1b randomized trial and follow-up study in Uganda of the blood-stage malaria vaccine candidate BK-SE36. PLoS One 8, e64073PubMedPubMedCentralCrossRefGoogle Scholar
- 28.Sheehy SH, Duncan CJ, Elias SC, Collins KA, Ewer KJ, Spencer AJ, Williams AR, Halstead FD, Moretz SE, Miura K et al (2011) Phase Ia clinical evaluation of the Plasmodium falciparum blood-stage antigen MSP1 in ChAd63 and MVA vaccine vectors. Mol Ther 19:2269–2276PubMedPubMedCentralCrossRefGoogle Scholar
- 29.Rogerson SJ, Hviid L, Duffy PE, Leke RF, Taylor DW (2007) Malaria in pregnancy: pathogenesis and immunity. Lancet Infect Dis 7:105–117PubMedCrossRefGoogle Scholar
- 30.Hviid L (2010) The role of Plasmodium falciparum variant surface antigens in protective immunity and vaccine development. Hum Vaccin 6:84–89PubMedCrossRefGoogle Scholar
- 31.Duncan CJ, Hill AV, Ellis RD (2012) Can growth inhibition assays (GIA) predict blood-stage malaria vaccine efficacy? Hum Vaccin Immunother 8:706–714PubMedPubMedCentralCrossRefGoogle Scholar
- 32.Miura K (2016) Progress and prospects for blood-stage malaria vaccines. Expert Rev Vaccines 15(6):765–781PubMedPubMedCentralCrossRefGoogle Scholar
- 33.Crompton PD, Miura K, Traore B, Kayentao K, Ongoiba A, Weiss G, Doumbo S, Doumtabe D, Kone Y, Huang CY et al (2009) In vitro growth inhibitory activity and malaria risk in a cohort study in mali. Infect Immun 78(2):737–745PubMedPubMedCentralCrossRefGoogle Scholar
- 34.Dutta S, Sullivan JS, Grady KK, Haynes JD, Komisar J, Batchelor AH, Soisson L, Diggs CL, Heppner DG, Lanar DE et al (2009) High antibody titer against apical membrane antigen-1 is required to protect against malaria in the Aotus model. PLoS One 4, e8138PubMedPubMedCentralCrossRefGoogle Scholar
- 35.Douglas AD, Williams AR, Illingworth JJ, Kamuyu G, Biswas S, Goodman AL, Wyllie DH, Crosnier C, Miura K, Wright GJ et al (2011) The blood-stage malaria antigen PfRH5 is susceptible to vaccine-inducible cross-strain neutralizing antibody. Nat Commun 2:601PubMedPubMedCentralCrossRefGoogle Scholar
- 36.Singh S, Miura K, Zhou H, Muratova O, Keegan B, Miles A, Martin LB, Saul AJ, Miller LH, Long CA (2006) Immunity to recombinant Plasmodium falciparum merozoite surface protein 1 (MSP1): protection in Aotus nancymai monkeys strongly correlates with anti-MSP1 antibody titer and in vitro parasite-inhibitory activity. Infect Immun 74:4573–4580PubMedPubMedCentralCrossRefGoogle Scholar
- 37.Plotkin SA (2008) Vaccines: correlates of vaccine-induced immunity. Clin Infect Dis 47:401–409PubMedCrossRefGoogle Scholar
- 38.Bouharoun-Tayoun H, Attanath P, Sabchareon A, Chongsuphajaisiddhi T, Druilhe P (1990) Antibodies that protect humans against Plasmodium falciparum blood stages do not on their own inhibit parasite growth and invasion in vitro, but act in cooperation with monocytes. J Exp Med 172:1633–1641PubMedCrossRefGoogle Scholar
- 39.Bouharoun-Tayoun H, Oeuvray C, Lunel F, Druilhe P (1995) Mechanisms underlying the monocyte-mediated antibody-dependent killing of Plasmodium falciparum asexual blood stages. J Exp Med 182:409–418PubMedCrossRefGoogle Scholar
- 40.Joos C, Marrama L, Polson HE, Corre S, Diatta AM, Diouf B, Trape JF, Tall A, Longacre S, Perraut R (2010) Clinical protection from falciparum malaria correlates with neutrophil respiratory bursts induced by merozoites opsonized with human serum antibodies. PLoS One 5, e9871PubMedPubMedCentralCrossRefGoogle Scholar
- 41.Hill DL, Eriksson EM, Carmagnac AB, Wilson DW, Cowman AF, Hansen DS, Schofield L (2012) Efficient measurement of opsonising antibodies to Plasmodium falciparum merozoites. PLoS One 7, e51692PubMedPubMedCentralCrossRefGoogle Scholar
- 42.Osier FH, Feng G, Boyle MJ, Langer C, Zhou J, Richards JS, McCallum FJ, Reiling L, Jaworowski A, Anders RF et al (2014) Opsonic phagocytosis of Plasmodium falciparum merozoites: mechanism in human immunity and a correlate of protection against malaria. BMC Med 12:108PubMedPubMedCentralCrossRefGoogle Scholar
- 43.Hill DL, Eriksson EM, Li Wai Suen CS, Chiu CY, Ryg-Cornejo V, Robinson LJ, Siba PM, Mueller I, Hansen DS, Schofield L (2013) Opsonising antibodies to P. falciparum merozoites associated with immunity to clinical malaria. PLoS One 8, e74627PubMedPubMedCentralCrossRefGoogle Scholar
- 44.Boyle MJ, Reiling L, Feng G, Langer C, Osier FH, Aspeling-Jones H, Cheng YS, Stubbs J, Tetteh KK, Conway DJ et al (2015) Human antibodies fix complement to inhibit Plasmodium falciparum invasion of erythrocytes and are associated with protection against malaria. Immunity 42:580–590PubMedPubMedCentralCrossRefGoogle Scholar
- 45.Bull PC, Lowe BS, Kortok M, Molyneux CS, Newbold CI, Marsh K (1998) Parasite antigens on the infected red cell surface are targets for naturally acquired immunity to malaria. Nat Med 4:358–360PubMedPubMedCentralCrossRefGoogle Scholar
- 46.Marsh K, Howard RJ (1986) Antigens induced on erythrocytes by Plasmodium falciparum: expression of diverse and conserved determinants. Science 231:150–153PubMedCrossRefGoogle Scholar
- 47.Duffy PE, Fried M (2003) Antibodies that inhibit Plasmodium falciparum adhesion to chondroitin sulfate A are associated with increased birth weight and the gestational age of newborns. Infect Immun 71:6620–6623PubMedPubMedCentralCrossRefGoogle Scholar
- 48.Saveria T, Duffy PE, Fried M (2015) Evaluation of pregnancy malaria vaccine candidates: the binding inhibition assay. Methods Mol Biol 1325:231–239PubMedCrossRefGoogle Scholar
- 49.Ghumra A, Khunrae P, Ataide R, Raza A, Rogerson SJ, Higgins MK, Rowe JA (2011) Immunisation with recombinant PfEMP1 domains elicits functional rosette-inhibiting and phagocytosis-inducing antibodies to Plasmodium falciparum. PLoS One 6, e16414PubMedPubMedCentralCrossRefGoogle Scholar
- 50.Silvie O, Franetich JF, Charrin S, Mueller MS, Siau A, Bodescot M, Rubinstein E, Hannoun L, Charoenvit Y, Kocken CH et al (2004) A role for apical membrane antigen 1 during invasion of hepatocytes by Plasmodium falciparum sporozoites. J Biol Chem 279:9490–9496PubMedCrossRefGoogle Scholar
- 51.Draper SJ, Goodman AL, Biswas S, Forbes EK, Moore AC, Gilbert SC, Hill AV (2009) Recombinant viral vaccines expressing merozoite surface protein-1 induce antibody- and T cell-mediated multistage protection against malaria. Cell Host Microbe 5:95–105PubMedPubMedCentralCrossRefGoogle Scholar
- 52.Pombo DJ, Lawrence G, Hirunpetcharat C, Rzepczyk C, Bryden M, Cloonan N, Anderson K, Mahakunkijcharoen Y, Martin LB, Wilson D et al (2002) Immunity to malaria after administration of ultra-low doses of red cells infected with Plasmodium falciparum. Lancet 360:610–617PubMedCrossRefGoogle Scholar
- 53.Edstein MD, Kotecka BM, Anderson KL, Pombo DJ, Kyle DE, Rieckmann KH, Good MF (2005) Lengthy antimalarial activity of atovaquone in human plasma following atovaquone-proguanil administration. Antimicrob Agents Chemother 49:4421–4422PubMedPubMedCentralCrossRefGoogle Scholar
- 54.Suss G, Eichmann K, Kury E, Linke A, Langhorne J (1988) Roles of CD4- and CD8-bearing T lymphocytes in the immune response to the erythrocytic stages of Plasmodium chabaudi. Infect Immun 56:3081–3088PubMedPubMedCentralGoogle Scholar
- 55.Mastelic B, do Rosario AP, Veldhoen M, Renauld JC, Jarra W, Sponaas AM, Roetynck S, Stockinger B, Langhorne J (2012) IL-22 protects against liver pathology and lethality of an experimental blood-stage malaria infection. Front Immunol 3:85PubMedPubMedCentralCrossRefGoogle Scholar
- 56.Freitas do Rosario AP, Lamb T, Spence P, Stephens R, Lang A, Roers A, Muller W, O’Garra A, Langhorne J (2012) IL-27 promotes IL-10 production by effector Th1 CD4+ T cells: a critical mechanism for protection from severe immunopathology during malaria infection. J Immunol 188:1178–1190PubMedCrossRefGoogle Scholar
- 57.Imai T, Ishida H, Suzue K, Taniguchi T, Okada H, Shimokawa C, Hisaeda H (2015) Cytotoxic activities of CD8+ T cells collaborate with macrophages to protect against blood-stage murine malaria. Elife 4, e04232PubMedCentralCrossRefGoogle Scholar
- 58.Biswas S, Spencer AJ, Forbes EK, Gilbert SC, Holder AA, Hill AV, Draper SJ (2012) Recombinant viral-vectored vaccines expressing Plasmodium chabaudi AS apical membrane antigen 1: mechanisms of vaccine-induced blood-stage protection. J Immunol 188:5041–5053PubMedPubMedCentralCrossRefGoogle Scholar
- 59.Sheehy SH, Duncan CJ, Elias SC, Choudhary P, Biswas S, Halstead FD, Collins KA, Edwards NJ, Douglas AD, Anagnostou NA et al (2012) ChAd63-MVA-vectored blood-stage malaria vaccines targeting MSP1 and AMA1: assessment of efficacy against mosquito bite challenge in humans. Mol Ther 20:2355–2368PubMedPubMedCentralCrossRefGoogle Scholar
- 60.Chuang I, Sedegah M, Cicatelli S, Spring M, Polhemus M, Tamminga C, Patterson N, Guerrero M, Bennett JW, McGrath S et al (2013) DNA prime/adenovirus boost malaria vaccine encoding P. falciparum CSP and AMA1 induces sterile protection associated with cell-mediated immunity. PLoS One 8, e55571PubMedPubMedCentralCrossRefGoogle Scholar
- 61.Perkins SL, Sarkar IN, Carter R (2007) The phylogeny of rodent malaria parasites: simultaneous analysis across three genomes. Infect Genet Evol 7:74–83PubMedCrossRefGoogle Scholar
- 62.Beaute-Lafitte A, Altemayer-Caillard V, Gonnet-Gonzalez F, Ramiaramanana L, Chabaud AG, Landau I (1994) The chemosensitivity of the rodent malarias—relationships with the biology of merozoites. Int J Parasitol 24:981–986PubMedCrossRefGoogle Scholar
- 63.Goodman AL, Forbes EK, Williams AR, Douglas AD, de Cassan SC, Bauza K, Biswas S, Dicks MD, Llewellyn D, Moore AC et al (2013) The utility of Plasmodium berghei as a rodent model for anti-merozoite malaria vaccine assessment. Sci Rep 3:1706PubMedPubMedCentralCrossRefGoogle Scholar
- 64.Siu E, Ploss A (2015) Modeling malaria in humanized mice: opportunities and challenges. Ann N Y Acad Sci 1342:29–36PubMedCrossRefGoogle Scholar
- 65.Collins WE, Galland GG, Sullivan JS, Morris CL (1994) Selection of different strains of Plasmodium falciparum for testing blood-stage vaccines in Aotus nancymai monkeys. Am J Trop Med Hyg 51:224–232PubMedGoogle Scholar
- 66.Collins WE (2002) Nonhuman primate models. II. Infection of Saimiri and Aotus monkeys with Plasmodium vivax. Methods Mol Med 72:85–92PubMedGoogle Scholar
- 67.Heppner DG, Cummings JF, Ockenhouse C, Kester KE, Lyon JA, Gordon DM (2001) New World monkey efficacy trials for malaria vaccine development: critical path or detour? Trends Parasitol 17:419–425PubMedCrossRefGoogle Scholar
- 68.Stowers AW, Miller LH (2001) Are trials in New World monkeys on the critical path for blood-stage malaria vaccine development? Trends Parasitol 17:415–419PubMedCrossRefGoogle Scholar
- 69.Epstein JE, Rao S, Williams F, Freilich D, Luke T, Sedegah M, de la Vega P, Sacci J, Richie TL, Hoffman SL (2007) Safety and clinical outcome of experimental challenge of human volunteers with Plasmodium falciparum-infected mosquitoes: an update. J Infect Dis 196:145–154PubMedCrossRefGoogle Scholar
- 70.Roestenberg M, O’Hara GA, Duncan CJ, Epstein JE, Edwards NJ, Scholzen A, van der Ven AJ, Hermsen CC, Hill AV, Sauerwein RW (2012) Comparison of clinical and parasitological data from controlled human malaria infection trials. PLoS One 7, e38434PubMedPubMedCentralCrossRefGoogle Scholar
- 71.Druilhe P, Perignon JL (1997) A hypothesis about the chronicity of malaria infection. Parasitol Today 13:353–357PubMedCrossRefGoogle Scholar
- 72.Douglas AD, Andrews L, Draper SJ, Bojang K, Milligan P, Gilbert SC, Imoukhuede EB, Hill AV (2011) Substantially reduced pre-patent parasite multiplication rates are associated with naturally acquired immunity to Plasmodium falciparum. J Infect Dis 203:1337–1340PubMedPubMedCentralCrossRefGoogle Scholar
- 73.Douglas AD, Edwards NJ, Duncan CJ, Thompson FM, Sheehy SH, O’Hara GA, Anagnostou N, Walther M, Webster DP, Dunachie SJ et al (2013) Comparison of modeling methods to determine liver-to-blood inocula and parasite multiplication rates during controlled human malaria infection. J Infect Dis 208:340–345PubMedPubMedCentralCrossRefGoogle Scholar
- 74.Cheng Q, Lawrence G, Reed C, Stowers A, Ranford-Cartwright L, Creasey A, Carter R, Saul A (1997) Measurement of Plasmodium falciparum growth rates in vivo: a test of malaria vaccines. Am J Trop Med Hyg 57:495–500PubMedGoogle Scholar
- 75.Sanderson F, Andrews L, Douglas AD, Hunt-Cooke A, Bejon P, Hill AV (2008) Blood-stage challenge for malaria vaccine efficacy trials: a pilot study with discussion of safety and potential value. Am J Trop Med Hyg 78:878–883PubMedGoogle Scholar
- 76.Remarque EJ, Faber BW, Kocken CH, Thomas AW (2008) Apical membrane antigen 1: a malaria vaccine candidate in review. Trends Parasitol 24:74–84PubMedCrossRefGoogle Scholar
- 77.Stowers AW, Kennedy MC, Keegan BP, Saul A, Long CA, Miller LH (2002) Vaccination of monkeys with recombinant Plasmodium falciparum apical membrane antigen 1 confers protection against blood-stage malaria. Infect Immun 70:6961–6967PubMedPubMedCentralCrossRefGoogle Scholar
- 78.Dutta S, Lalitha PV, Ware LA, Barbosa A, Moch JK, Vassell MA, Fileta BB, Kitov S, Kolodny N, Heppner DG et al (2002) Purification, characterization, and immunogenicity of the refolded ectodomain of the Plasmodium falciparum apical membrane antigen 1 expressed in Escherichia coli. Infect Immun 70:3101–3110PubMedPubMedCentralCrossRefGoogle Scholar
- 79.Srinivasan P, Ekanem E, Diouf A, Tonkin ML, Miura K, Boulanger MJ, Long CA, Narum DL, Miller LH (2014) Immunization with a functional protein complex required for erythrocyte invasion protects against lethal malaria. Proc Natl Acad Sci U S A 111:10311–10316PubMedPubMedCentralCrossRefGoogle Scholar
- 80.Harris KS, Adda CG, Khore M, Drew DR, Valentini-Gatt A, Fowkes FJ, Beeson JG, Dutta S, Anders RF, Foley M (2014) Use of immunodampening to overcome diversity in the malarial vaccine candidate apical membrane antigen 1. Infect Immun 82:4707–4717PubMedPubMedCentralCrossRefGoogle Scholar
- 81.Remarque EJ, Faber BW, Kocken CH, Thomas AW (2008) A diversity-covering approach to immunization with Plasmodium falciparum apical membrane antigen 1 induces broader allelic recognition and growth inhibition responses in rabbits. Infect Immun 76:2660–2670PubMedPubMedCentralCrossRefGoogle Scholar
- 82.Lyon JA, Angov E, Fay MP, Sullivan JS, Girourd AS, Robinson SJ, Bergmann-Leitner ES, Duncan EH, Darko CA, Collins WE et al (2008) Protection induced by Plasmodium falciparum MSP1(42) is strain-specific, antigen and adjuvant dependent, and correlates with antibody responses. PLoS One 3, e2830PubMedPubMedCentralCrossRefGoogle Scholar
- 83.Ogutu BR, Apollo OJ, McKinney D, Okoth W, Siangla J, Dubovsky F, Tucker K, Waitumbi JN, Diggs C, Wittes J et al (2009) Blood stage malaria vaccine eliciting high antigen-specific antibody concentrations confers no protection to young children in Western Kenya. PLoS One 4, e4708PubMedPubMedCentralCrossRefGoogle Scholar
- 84.Zong S, Kron MW, Epp C, Engler T, Bujard H, Kochanek S, Kreppel F (2011) DeltaE1 and high-capacity adenoviral vectors expressing full-length codon-optimized merozoite surface protein 1 for vaccination against Plasmodium falciparum. J Gene Med 13:670–679PubMedCrossRefGoogle Scholar
- 85.Crosnier C, Wanaguru M, McDade B, Osier FH, Marsh K, Rayner JC, Wright GJA (2013) A library of functional recombinant cell-surface and secreted P. falciparum merozoite proteins. Mol Cell Proteomics 12:3976–3986PubMedPubMedCentralCrossRefGoogle Scholar
- 86.Oeuvray C, Bouharoun-Tayoun H, Gras-Masse H, Bottius E, Kaidoh T, Aikawa M, Filgueira MC, Tartar A, Druilhe P (1994) Merozoite surface protein-3: a malaria protein inducing antibodies that promote Plasmodium falciparum killing by cooperation with blood monocytes. Blood 84:1594–1602PubMedGoogle Scholar
- 87.Badell E, Oeuvray C, Moreno A, Soe S, van Rooijen N, Bouzidi A, Druilhe P (2000) Human malaria in immunocompromised mice: an in vivo model to study defense mechanisms against Plasmodium falciparum. J Exp Med 192:1653–1660PubMedPubMedCentralCrossRefGoogle Scholar
- 88.Hisaeda H, Saul A, Reece JJ, Kennedy MC, Long CA, Miller LH, Stowers AW (2002) Merozoite surface protein 3 and protection against malaria in Aotus nancymai monkeys. J Infect Dis 185:657–664PubMedCrossRefGoogle Scholar
- 89.Tsai CW, Duggan PF, Jin AJ, Macdonald NJ, Kotova S, Lebowitz J, Hurt DE, Shimp RL Jr, Lambert L, Miller LH et al (2009) Characterization of a protective Escherichia coli-expressed Plasmodium falciparum merozoite surface protein 3 indicates a non-linear, multi-domain structure. Mol Biochem Parasitol 164:45–56PubMedCrossRefGoogle Scholar
- 90.Horii T, Shirai H, Jie L, Ishii KJ, Palacpac NQ, Tougan T, Hato M, Ohta N, Bobogare A, Arakaki N et al (2010) Evidences of protection against blood-stage infection of Plasmodium falciparum by the novel protein vaccine SE36. Parasitol Int 59:380–386PubMedCrossRefGoogle Scholar
- 91.Stallmach R, Kavishwar M, Withers-Martinez C, Hackett F, Collins CR, Howell SA, Yeoh S, Knuepfer E, Atid AJ, Holder AA et al (2015) Plasmodium falciparum SERA5 plays a non-enzymatic role in the malarial asexual blood-stage lifecycle. Mol Microbiol 96:368–387PubMedPubMedCentralCrossRefGoogle Scholar
- 92.Tanabe K, Arisue N, Palacpac NM, Yagi M, Tougan T, Honma H, Ferreira MU, Farnert A, Bjorkman A, Kaneko A et al (2012) Geographic differentiation of polymorphism in the Plasmodium falciparum malaria vaccine candidate gene SERA5. Vaccine 30:1583–1593PubMedCrossRefGoogle Scholar
- 93.Tham WH, Healer J, Cowman AF (2012) Erythrocyte and reticulocyte binding-like proteins of Plasmodium falciparum. Trends Parasitol 28:23–30PubMedCrossRefGoogle Scholar
- 94.Wright GJ, Rayner JC (2014) Plasmodium falciparum erythrocyte invasion: combining function with immune evasion. PLoS Pathog 10, e1003943PubMedPubMedCentralCrossRefGoogle Scholar
- 95.Jones TR, Stroncek DF, Gozalo AS, Obaldia N 3rd, Andersen EM, Lucas C, Narum DL, Magill AJ, Sim BK, Hoffman SL (2002) Anemia in parasite- and recombinant protein-immunized aotus monkeys infected with Plasmodium falciparum. Am J Trop Med Hyg 66:672–679PubMedGoogle Scholar
- 96.El Sahly HM, Patel SM, Atmar RL, Lanford TA, Dube T, Thompson D, Sim BK, Long C, Keitel WA (2010) Safety and immunogenicity of a recombinant nonglycosylated erythrocyte binding antigen 175 Region II malaria vaccine in healthy adults living in an area where malaria is not endemic. Clin Vaccine Immunol 17:1552–1559PubMedPubMedCentralCrossRefGoogle Scholar
- 97.Stubbs J, Simpson KM, Triglia T, Plouffe D, Tonkin CJ, Duraisingh MT, Maier AG, Winzeler EA, Cowman AF (2005) Molecular mechanism for switching of P. falciparum invasion pathways into human erythrocytes. Science 309:1384–1387PubMedCrossRefGoogle Scholar
- 98.Baum J, Chen L, Healer J, Lopaticki S, Boyle M, Triglia T, Ehlgen F, Ralph SA, Beeson JG, Cowman AF (2009) Reticulocyte-binding protein homologue 5—an essential adhesin involved in invasion of human erythrocytes by Plasmodium falciparum. Int J Parasitol 39:371–380PubMedCrossRefGoogle Scholar
- 99.Crosnier C, Bustamante LY, Bartholdson SJ, Bei AK, Theron M, Uchikawa M, Mboup S, Ndir O, Kwiatkowski DP, Duraisingh MT et al (2011) Basigin is a receptor essential for erythrocyte invasion by Plasmodium falciparum. Nature 480:534–537PubMedPubMedCentralGoogle Scholar
- 100.Villard V, Agak GW, Frank G, Jafarshad A, Servis C, Nebie I, Sirima SB, Felger I, Arevalo-Herrera M, Herrera S et al (2007) Rapid identification of malaria vaccine candidates based on alpha-helical coiled coil protein motif. PLoS One 2, e645PubMedPubMedCentralCrossRefGoogle Scholar
- 101.Olugbile S, Kulangara C, Bang G, Bertholet S, Suzarte E, Villard V, Frank G, Audran R, Razaname A, Nebie I et al (2009) Vaccine potentials of an intrinsically unstructured fragment derived from the blood stage-associated Plasmodium falciparum protein PFF0165c. Infect Immun 77:5701–5709PubMedPubMedCentralCrossRefGoogle Scholar
- 102.Mueller I, Shakri AR, Chitnis CE (2015) Development of vaccines for Plasmodium vivax malaria. Vaccine 33:7489–7495PubMedCrossRefGoogle Scholar
- 103.Russell B, Suwanarusk R, Borlon C, Costa FT, Chu CS, Rijken MJ, Sriprawat K, Warter L, Koh EG, Malleret B et al (2011) A reliable ex vivo invasion assay of human reticulocytes by Plasmodium vivax. Blood 118:e74–e81PubMedPubMedCentralCrossRefGoogle Scholar
- 104.Collins WE, Sullivan JS, Strobert E, Galland GG, Williams A, Nace D, Williams T, Barnwell JW (2009) Studies on the Salvador I strain of Plasmodium vivax in non-human primates and anopheline mosquitoes. Am J Trop Med Hyg 80:228–235PubMedGoogle Scholar
- 105.Dutta S, Kaushal DC, Ware LA, Puri SK, Kaushal NA, Narula A, Upadhyaya DS, Lanar DE (2005) Merozoite surface protein 1 of Plasmodium vivax induces a protective response against Plasmodium cynomolgi challenge in rhesus monkeys. Infect Immun 73:5936–5944PubMedPubMedCentralCrossRefGoogle Scholar
- 106.Bennett JW, Pybus BS, Yadava A, Tosh D, Sousa JC, McCarthy WF, Deye G, Melendez V, Ockenhouse CF (2013) Primaquine failure and cytochrome P-450 2D6 in Plasmodium vivax malaria. N Engl J Med 369:1381–1382PubMedCrossRefGoogle Scholar
- 107.Arevalo-Herrera M, Forero-Pena DA, Rubiano K, Gomez-Hincapie J, Martinez NL, Lopez-Perez M, Castellanos A, Cespedes N, Palacios R, Onate JM et al (2014) Plasmodium vivax sporozoite challenge in malaria-naive and semi-immune Colombian volunteers. PLoS One 9, e99754PubMedPubMedCentralCrossRefGoogle Scholar
- 108.Miller LH, Mason SJ, Clyde DF, McGinniss MH (1976) The resistance factor to Plasmodium vivax in blacks. The Duffy-blood-group genotype, FyFy. N Engl J Med 295:302–304PubMedCrossRefGoogle Scholar
- 109.Grimberg BT, Udomsangpetch R, Xainli J, McHenry A, Panichakul T, Sattabongkot J, Cui L, Bockarie M, Chitnis C, Adams J et al (2007) Plasmodium vivax invasion of human erythrocytes inhibited by antibodies directed against the Duffy binding protein. PLoS Med 4, e337PubMedPubMedCentralCrossRefGoogle Scholar
- 110.Arevalo-Herrera M, Castellanos A, Yazdani SS, Shakri AR, Chitnis CE, Dominik R, Herrera S (2005) Immunogenicity and protective efficacy of recombinant vaccine based on the receptor-binding domain of the Plasmodium vivax Duffy binding protein in Aotus monkeys. Am J Trop Med Hyg 73:25–31PubMedGoogle Scholar
- 111.de Cassan SC, Shakri AR, Llewellyn D, Elias SC, Cho JS, Goodman AL, Jin J, Douglas AD, Suwanarusk R, Nosten FH et al (2015) Preclinical assessment of viral vectored and protein vaccines targeting the duffy-binding protein region II of Plasmodium vivax. Front Immunol 6:348PubMedPubMedCentralCrossRefGoogle Scholar
- 112.White MT, Bejon P, Olotu A, Griffin JT, Bojang K, Lusingu J, Salim N, Abdulla S, Otsyula N, Agnandji ST et al (2014) A combined analysis of immunogenicity, antibody kinetics and vaccine efficacy from phase 2 trials of the RTS, S malaria vaccine. BMC Med 12:117PubMedPubMedCentralCrossRefGoogle Scholar
- 113.Tsuboi T, Takeo S, Iriko H, Jin L, Tsuchimochi M, Matsuda S, Han ET, Otsuki H, Kaneko O, Sattabongkot J et al (2008) Wheat germ cell-free system-based production of malaria proteins for discovery of novel vaccine candidates. Infect Immun 76:1702–1708PubMedPubMedCentralCrossRefGoogle Scholar
- 114.Lau CK, Turner L, Jespersen JS, Lowe ED, Petersen B, Wang CW, Petersen JE, Lusingu J, Theander TG, Lavstsen T et al (2015) Structural conservation despite huge sequence diversity allows EPCR binding by the PfEMP1 family implicated in severe childhood malaria. Cell Host Microbe 17:118–129PubMedPubMedCentralCrossRefGoogle Scholar
- 115.Ghumra A, Semblat JP, Ataide R, Kifude C, Adams Y, Claessens A, Anong DN, Bull PC, Fennell C, Arman M et al (2012) Induction of strain-transcending antibodies against Group A PfEMP1 surface antigens from virulent malaria parasites. PLoS Pathog 8, e1002665PubMedPubMedCentralCrossRefGoogle Scholar
- 116.Baruch DI, Gamain B, Barnwell JW, Sullivan JS, Stowers A, Galland GG, Miller LH, Collins WE (2002) Immunization of Aotus monkeys with a functional domain of the Plasmodium falciparum variant antigen induces protection against a lethal parasite line. Proc Natl Acad Sci U S A 99:3860–3865PubMedPubMedCentralCrossRefGoogle Scholar
- 117.Sampath S, Carrico C, Janes J, Gurumoorthy S, Gibson C, Melcher M, Chitnis CE, Wang R, Schief WR, Smith JD (2013) Glycan masking of Plasmodium vivax Duffy Binding Protein for probing protein binding function and vaccine development. PLoS Pathog 9, e1003420PubMedPubMedCentralCrossRefGoogle Scholar
- 118.Fried M, Duffy PE (2015) Designing a VAR2CSA-based vaccine to prevent placental malaria. Vaccine 33:7483–7488PubMedPubMedCentralCrossRefGoogle Scholar
- 119.Barfod L, Dobrilovic T, Magistrado P, Khunrae P, Viwami F, Bruun J, Dahlback M, Bernasconi NL, Fried M, John D et al (2010) Chondroitin sulfate A-adhering Plasmodium falciparum-infected erythrocytes express functionally important antibody epitopes shared by multiple variants. J Immunol 185:7553–7561PubMedPubMedCentralCrossRefGoogle Scholar
- 120.Brune KD, Leneghan DB, Brian IJ, Ishizuka AS, Bachmann MF, Draper SJ, Biswas S, Howarth M (2016) Plug-and-Display: decoration of Virus-Like Particles via isopeptide bonds for modular immunization. Sci Rep 6:19234PubMedPubMedCentralCrossRefGoogle Scholar
- 121.Moon JJ, Suh H, Li AV, Ockenhouse CF, Yadava A, Irvine DJ (2012) Enhancing humoral responses to a malaria antigen with nanoparticle vaccines that expand Tfh cells and promote germinal center induction. Proc Natl Acad Sci U S A 109:1080–1085PubMedPubMedCentralCrossRefGoogle Scholar
- 122.Balazs AB, Chen J, Hong CM, Rao DS, Yang L, Baltimore D (2012) Antibody-based protection against HIV infection by vectored immunoprophylaxis. Nature 481:81–84CrossRefGoogle Scholar