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Review

The GMZ2 malaria vaccine: from concept to efficacy in humans

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Pages 907-917 | Received 03 Apr 2017, Accepted 11 Jul 2017, Published online: 21 Jul 2017

References

  • WHO. World Malaria Report 2015. (Ed.(Eds) (2015)
  • Sharma VP. Re-emergence of malaria in India. Indian J Med Res. 1996;103:26–45.
  • Moiroux N, Gomez MB, Pennetier C, et al. Changes in Anopheles funestus biting behavior following universal coverage of long-lasting insecticidal nets in Benin. J Infect Dis. 2012;206(10):1622–1629.
  • Molineaux L, Gramiccia G. The Gharki project: research on the epidemiology and control of malaria in Sudan Savanna of West Africa. Geneva: World Health Organization; 1980.
  • Morrison C. Landmark green light for Mosquirix malaria vaccine. Nat Biotechnol. 2015;33(10):1015–1016.
  • Rts SCTP. Efficacy and safety of RTS,S/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: final results of a phase 3, individually randomised, controlled trial. Lancet. 2015;386(9988):31–45.
  • Olotu A, Fegan G, Wambua J, et al. Seven-year efficacy of RTS,S/AS01 malaria vaccine among young African children. N Engl J Med. 2016;374(26):2519–2529.
  • Seder RA, Chang LJ, Enama ME, et al. Protection against malaria by intravenous immunization with a nonreplicating sporozoite vaccine. Science. 2013;341(6152):1359–1365.
  • Mordmuller B, Surat G, Lagler H, et al. Sterile protection against human malaria by chemoattenuated PfSPZ vaccine. Nature. 2017;542(7642):445–449.
  • Sissoko MS, Healy SA, Katile A, et al. Safety and efficacy of PfSPZ vaccine against Plasmodium falciparum via direct venous inoculation in healthy malaria-exposed adults in Mali: a randomised, double-blind phase 1 trial. Lancet Infect Dis. 2017;17(5):498–509.
  • Bijker EM, Bastiaens GJ, Teirlinck AC, et al. 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):7862–7867.
  • Coleman PG, Perry BD, Woolhouse ME. Endemic stability–a veterinary idea applied to human public health. Lancet. 2001;357(9264):1284–1286.
  • Schwartz L, Brown GV, Genton B, et al. A review of malaria vaccine clinical projects based on the WHO rainbow table. Malar J. 2012;11(11).
  • Salanti A, Dahlback M, Turner L, et al. Evidence for the involvement of VAR2CSA in pregnancy-associated malaria. J Exp Med. 2004;200(9):1197–1203.
  • Holder AA. The carboxy-terminus of merozoite surface protein 1: structure, specific antibodies and immunity to malaria. Parasitology. 2009;136(12):1445–1456.
  • Hodder AN, Crewther PE, Anders RF. Specificity of the protective antibody response to apical membrane antigen 1. Infect Immun. 2001;69(5):3286–3294.
  • Cohen S, McGregor A, Carrington S. Gamma globulin and aquired immunity to human malaria. Nature. 1961;192:733–737.
  • Lin CS, Uboldi AD, Epp C, et al. Multiple Plasmodium falciparum merozoite surface protein 1 complexes mediate merozoite binding to human erythrocytes. J Biol Chem. 2016;291(14):7703–7715.
  • Paul G, Deshmukh A, Kaur I, et al. A novel Pfs38 protein complex on the surface of Plasmodium falciparum blood-stage merozoites. Malar J. 2017;16(1):79.
  • Thomas AW, Deans JA, Mitchell GH, et al. The fab fragments of monoclonal IgG to a merozoite surface antigen inhibit Plasmodium knowlesi invasion of erythrocytes. Mol Biochem Parasitol. 1984;13(2):187–199.
  • Holder AA, Freeman RR. Immunization against blood-stage rodent malaria using purified parasite antigens. Nature. 1981;294(5839):361–364.
  • Ogutu BR, Apollo OJ, McKinney D, et al. Blood stage malaria vaccine eliciting high antigen-specific antibody concentrations confers no protection to young children in western Kenya. PLoS One. 2009;4(3):e4708.
  • Sagara I, Dicko A, Ellis RD, et al. A randomized controlled phase 2 trial of the blood stage AMA1-C1/Alhydrogel malaria vaccine in children in Mali. Vaccine. 2009;27(23):3090–3098.
  • Genton B, Betuela I, Felger I, et al. 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. 2002;185(6):820–827.
  • Thera MA, Doumbo OK, Coulibaly D, et al. A field trial to assess a blood-stage malaria vaccine. N Engl J Med. 2011;365(11):1004–1013.
  • Srinivasan P, Ekanem E, Diouf A, et al. Immunization with a functional protein complex required for erythrocyte invasion protects against lethal malaria. Proc Natl Acad Sci U S A. 2014;111(28):10311–10316.
  • Sergent E. [Definition of immunity & premunition]. Annales De l’Institut Pasteur. 1950;79(5):786–797.
  • Oeuvray C, Bouharoun-Tayoun H, Gras-Masse H, et al. Merozoite surface protein−3: a malaria protein inducing antibodies that promote Plasmodium falciparum killing by cooperation with blood monocytes. Blood. 1994;84:1594–1602.
  • Theisen M, Soe S, Oeuvray C, et al. The glutamate-rich protein (GLURP) of Plasmodium falciparum is a target for antibody-dependent monocyte-mediated inhibition of parasite growth in vitro. Infect Immun. 1998;66(1):11–17.
  • Sabchareon A, Burnouf T, Ouattara D, et al. Parasitologic and clinical human response to immunoglobulin administration in falciparum malaria. Am J Trop Med Hyg. 1991;45:297–308.
  • McGregor IA, Carrington SP, Cohen S. Treatment of East African P. falciparum malaria with West African gammaglobulin. Trans R Soc Trop Med Hyg. 1963;57:170–175.
  • Dodoo D, Theander TG, Kurtzhals J, et al. Antibody levels to conserved parts of Plasmodium falciparum merozoite surface protein 1 (PfMSP1) Ghanaian children are not associated with protection from clinical malaria. Infect Immun. 1999;67:2131–2137.
  • Fowkes FJ, Richards JS, Simpson JA, et al. The relationship between anti-merozoite antibodies and incidence of Plasmodium falciparum malaria: a systematic review and meta-analysis. PLoS Med. 2010;7(1):e1000218.
  • Meraldi V, Nebie I, Tiono AB, et al. Natural antibody response to Plasmodium falciparum Exp−1, MSP−3 and GLURP long synthetic peptides and association with protection. Parasite Immunol. 2004;26(6−7):265–272.
  • Nebie I, Diarra A, Ouedraogo A, et al. Humoral responses to Plasmodium falciparum blood-stage antigens and association with incidence of clinical malaria in children living in an area of seasonal malaria transmission in Burkina Faso, West Africa. Infect Immun. 2008;76(2):759–766.
  • Nebie I, Tiono AB, Diallo DA, et al. Do antibody responses to malaria vaccine candidates influenced by the level of malaria transmission protect from malaria? Trop Med Int Health. 2008;13(2):229–237.
  • Diarra A, Nebie I, Tiono A, et al. Antibodies to malaria vaccine candidates are associated with chloroquine or sulphadoxine/pyrimethamine treatment efficacy in children in an endemic area of Burkina Faso. Malar J. 2012;11:79.
  • Kangoye DT, Nebie I, Yaro JB, et al. Plasmodium falciparum malaria in children aged 0−2 years: the role of foetal haemoglobin and maternal antibodies to two asexual malaria vaccine candidates (MSP3 and GLURP). PLoS One. 2014;9(9):e107965.
  • Guiyedi V, Becavin C, Herbert F, et al. Asymptomatic Plasmodium falciparum infection in children is associated with increased auto-antibody production, high IL−10 plasma levels and antibodies to merozoite surface protein 3. Malar J. 2015;14:162.
  • Dodoo D, Theisen M, Kurtzhals JA, et al. Naturally acquired antibodies to the glutamate-rich protein are associated with protection against Plasmodium falciparum malaria. J Infect Dis. 2000;181(3):1202–1205.
  • Dodoo D, Aikins A, Kusi KA, et al. Cohort study of the association of antibody levels to AMA1, MSP119, MSP3 and GLURP with protection from clinical malaria in Ghanaian children. Malar J. 2008;7:142.
  • Dodoo D, Atuguba F, Bosomprah S, et al. Antibody levels to multiple malaria vaccine candidate antigens in relation to clinical malaria episodes in children in the Kasena-Nankana district of northern Ghana. Malar J. 2011;10(108).
  • Theisen M, Dodoo D, Balde AT, et al. Selection of long GLURP synthetic peptides for vaccine development: antigenicity, relationship with clinical protection and immunogenicity. Infect Immun. 2001;69:5223–5229.
  • Osier FH, Fegan G, Polley SD, et al. Breadth and magnitude of antibody responses to multiple Plasmodium falciparum merozoite antigens are associated with protection from clinical malaria. Infect Immun. 2008;76(5):2240–2248.
  • Osier FH, Polley SD, Mwangi T, et al. Naturally acquired antibodies to polymorphic and conserved epitopes of Plasmodium falciparum merozoite surface protein 3. Parasite Immunol. 2007;29(8):387–394.
  • Soe S, Theisen M, Roussilhon C, et al. Association between protection against clinical malaria and antibodies to merozoite surface antigens in an area of hyperendemicity in Myanmar: complementarity between responses to merozoite surface protein 3 and the 220-kilodalton glutamate-rich protein. Infect Immun. 2004;72(1):247–252.
  • Oeuvray C, Theisen M, Rogier C, et al. Cytophilic immunoglobulin responses to Plasmodium falciparum glutamate-rich protein are correlated with protection against clinical malaria in Dielmo, Senegal. Infect Immun. 2000;68(5):2617–2620.
  • Courtin D, Oesterholt M, Huismans H, et al. The quantity and quality of African children’s IgG responses to merozoite surface antigens reflect protection against Plasmodium falciparum malaria. PLoS One. 2009;4(10):e7590.
  • Roussilhon C, Oeuvray C, Muller-Graf C, et al. Long-term clinical protection from falciparum malaria is strongly associated with IgG3 antibodies to merozoite surface protein 3. PLoS Med. 2007;4(11):e320.
  • Roussilhon C, Brasseur P, Agnamey P, et al. Understanding human-Plasmodium falciparum immune interactions uncovers the immunological role of worms. PLoS One. 2010;5(2):e9309.
  • Iriemenam NC, Khirelsied AH, Nasr A, et al. Antibody responses to a panel of Plasmodium falciparum malaria blood-stage antigens in relation to clinical disease outcome in Sudan. Vaccine. 2009;27(1):62–71.
  • Lusingu JP, Vestergaard LS, Alifrangis M, et al. Cytophilic antibodies to Plasmodium falciparum glutamate rich protein are associated with malaria protection in an area of holoendemic transmission. Malar J. 2005;4:48.
  • Dziegiel M, Rowe P, Bennett S, et al. Immunoglobulin M and G antibody responses to Plasmodium falciparum glutamate-rich protein: correlation with clinical immunity in Gambian children. Infect Immun. 1993;61(1):103–108.
  • Polley SD, Tetteh KK, Lloyd JM, et al. Plasmodium falciparum merozoite surface protein 3 is a target of allele-specific immunity and alleles are maintained by natural selection. J Infect Dis. 2007;195(2):279–287.
  • Greenhouse B, Ho B, Hubbard A, et al. Antibodies to Plasmodium falciparum antigens predict a higher risk of malaria but protection from symptoms once parasitemic. J Infect Dis. 2011;204(1):19–26.
  • Keh CE, Jha AR, Nzarubara B, et al. Associations between antibodies to a panel of Plasmodium falciparum specific antigens and response to sub-optimal antimalarial therapy in Kampala, Uganda. PLoS One. 2012;7(12):e52571.
  • Adu B, Jepsen MP, Gerds TA, et al. Fc gamma receptor 3B (FCGR3B-c.233C>A-rs5030738) polymorphism modifies the protective effect of malaria specific antibodies in Ghanaian children. J Infect Dis. 2014;209(2):285–289.
  • Adu B, Cherif MK, Bosomprah S, et al. Antibody levels against GLURP R2, MSP1 block 2 hybrid and AS202.11 and the risk of malaria in children living in hyperendemic (Burkina Faso) and hypo-endemic (Ghana) areas. Malar J. 2016;15:123.
  • Borre MB, Dziegiel M, Hogh B, et al. Primary structure and localization of a conserved immunogenic Plasmodium falciparum glutamate rich protein (GLURP) expressed in both the preerythrocytic and erythrocytic stages of the vertebrate life cycle. Mol Biochem Parasitol. 1991;49(1):119–131.
  • McColl DJ, Silva A, Foley M, et al. Molecular variation in a novel polymorphic antigen associated with Plasmodium falciparum merozoites. Mol Biochem Parasitol. 1994;68(1):53–67.
  • Holder AA, Blackman MJ, Borre M, et al. Malaria parasites and erythrocyte invasion. Biochem Soc Trans. 1994;22(2):291–295.
  • Osier FH, Feng G, Boyle MJ, et al. Opsonic phagocytosis of Plasmodium falciparum merozoites: mechanism in human immunity and a correlate of protection against malaria. BMC Med. 2014;12:108.
  • Kana IH, Adu B, Tiendrebeogo RW, et al. Naturally acquired antibodies target the glutamate-rich protein on intact merozoites and predict protection against febrile malaria. J Infect Dis. 2017;215:623–630.
  • Tiendrebeogo RW, Adu B, Singh SK, et al. Antibody-dependent cellular inhibition is associated with reduced risk against febrile malaria in a longitudinal cohort study involving Ghanaian children. Open Forum Infect Dis. 2015;2(2).
  • Bouharoun-Tayoun H, Oeuvray C, Lunel F, et al. Mechanisms underlying the monocyte-mediated antibody-dependent killing of Plasmodium falciparum asexual blood stages. J Exp Med. 1995;182:409–418.
  • Jafarshad A, Dziegiel MH, Lundquist R, et al. A novel antibody-dependent cellular cytotoxicity mechanism involved in defense against malaria requires costimulation of monocytes FcgammaRII and FcgammaRIII. J Immunol. 2007;178(5):3099–3106.
  • Bouharoun-Tayoun H, Attanath P, Sabchareon A, et al. 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. 1990;172:1633–1641.
  • Khusmith S, Druilhe P. Antibody-dependent ingestion of P. falciparum merozoites by human blood monocytes. Parasite Immunol. 1983;5:357–368.
  • Stricker K, Vuust J, Jepsen S, et al. Conservation and heterogeneity of the Glutamate-rich protein (GLURP) among field isolates and laboratory lines of Plasmodium falciparum. Mol Biochem Parasitol. 2000;111:123–130.
  • Theisen M, Soe S, Brunstedt K, et al. A Plasmodium falciparum GLURP-MSP3 chimeric protein; expression in Lactococcus lactis, immunogenicity and induction of biologically active antibodies. Vaccine. 2004;22(9−10):1188–1198.
  • Theisen M, Vuust J, Gottschau A, et al. Antigenicity and immunogenicity of recombinant glutamate-rich protein of Plasmodium falciparum expressed in Escherichia coli. Clin Diagn Lab Immunol. 1995;2(1):30–34.
  • Gardner MJ, Hall N, Fung E, et al. Genome sequence of the human malaria parasite Plasmodium falciparum. Nature. 2002;419(6906):498–511.
  • Burgess BR, Schuck P, Garboczi DN. Dissection of merozoite surface protein 3, a representative of a family of Plasmodium falciparum surface proteins, reveals an oligomeric and highly elongated molecule. J Biol Chem. 2005;280(44):37236–37245.
  • Imam M, Singh S, Kaushik NK, et al. Plasmodium falciparum merozoite surface protein 3: oligomerization, self-assembly, and heme complex formation. J Biol Chem. 2014;289(7):3856–3868.
  • Frech C, Chen N. Genome comparison of human and non-human malaria parasites reveals species subset-specific genes potentially linked to human disease. PLoS Comput Biol. 2011;7(12):e1002320.
  • Bredius RG, De Vries CE, Troelstra A, et al. Phagocytosis of Staphylococcus aureus and Haemophilus influenzae type B opsonized with polyclonal human IgG1 and IgG2 antibodies. Functional hFc gamma RIIa polymorphism to IgG2. J Immunol. 1993;151(3):1463–1472.
  • Adu B, Dodoo D, Adukpo S, et al. Fc gamma receptor IIIB (FcgammaRIIIB) polymorphisms are associated with clinical malaria in Ghanaian children. PLoS One. 2012;7(9):e46197.
  • Audran R, Cachat M, Lurati F, et al. Phase I malaria vaccine trial with a long synthetic peptide derived from the merozoite surface protein 3 antigen. Infect Immun. 2005;73(12):8017–8026.
  • Hermsen CC, Verhage DF, Telgt DS, et al. Glutamate-rich protein (GLURP) induces antibodies that inhibit in vitro growth of Plasmodium falciparum in a phase 1 malaria vaccine trial. Vaccine. 2007;25(15):2930–2940.
  • Mamo H, Esen M, Ajua A, et al. Humoral immune response to Plasmodium falciparum vaccine candidate GMZ2 and its components in populations naturally exposed to seasonal malaria in Ethiopia. Malar J. 2013;12:51.
  • Lubeck MD, Steplewski Z, Baglia F, et al. The interaction of murine IgG subclass proteins with human monocyte Fc receptors. J Immunol. 1985;135(2):1299–1304.
  • Singh S, Soe S, Mejia JP, et al. Identification of a conserved region of Plasmodium falciparum MSP3 targeted by biologically active antibodies to improve vaccine design. J Infect Dis. 2004;190(5):1010–1018.
  • Bang G, Prieur E, Roussilhon C, et al. Pre-clinical assessment of novel multivalent MSP3 malaria vaccine constructs. PLoS One. 2011;6(12):e28165.
  • Theisen M, Roeffen W, Singh SK, et al. A multi-stage malaria vaccine candidate targeting both transmission and asexual parasite life-cycle stages. Vaccine. 2014;32(22):2623–2630.
  • Hisaeda H, Saul A, Reece JJ, et al. Merozoite surface protein 3 and protection against malaria in Aotus nancymai monkeys. J Infect Diseases. 2002;185:657–664.
  • Carvalho LJ, Oliveira SG, Theisen M, et al. Immunization of Saimiri sciureus monkeys with Plasmodium falciparum merozoite surface protein−3 and glutamate-rich protein suggests that protection is related to antibody levels. Scand J Immunol. 2004;59(4):363–372.
  • Carvalho LJ, Alves FA, Bianco C Jr, et al. Immunization of Saimiri sciureus monkeys with a recombinant hybrid protein derived from the Plasmodium falciparum antigen glutamate-rich protein and merozoite surface protein 3 can induce partial protection with Freund and Montanide ISA720 adjuvants. Clin Diagn Lab Immunol. 2005;12(2):242–248.
  • Esen M, Kremsner PG, Schleucher R, et al. Safety and immunogenicity of GMZ2 - a MSP3-GLURP fusion protein malaria vaccine candidate. Vaccine. 2009;27(49):6862–6868.
  • Mordmuller B, Szywon K, Greutelaers B, et al. Safety and immunogenicity of the malaria vaccine candidate GMZ2 in malaria-exposed, adult individuals from Lambarene, Gabon. Vaccine. 2010;28(41):6698–6703.
  • Belard S, Issifou S, Hounkpatin AB, et al. A randomized controlled phase Ib trial of the malaria vaccine candidate GMZ2 in African children. PLoS One. 2011;6(7):e22525.
  • Jepsen MP, Jogdand PS, Singh SK, et al. The malaria vaccine candidate GMZ2 elicits functional antibodies in individuals from malaria endemic and non-endemic areas. J Infect Dis. 2013;208(3):479–488.
  • Sirima SB, Mordmuller B, Milligan P, et al. A phase 2b randomized, controlled trial of the efficacy of the GMZ2 malaria vaccine in African children. Vaccine. 2016;34(38):4536–4542.
  • Reed SG, Orr MT, Fox CB. Key roles of adjuvants in modern vaccines. Nat Med. 2013;19(12):1597–1608.
  • Garcon N, Chomez P, Van Mechelen M. GlaxoSmithKline Adjuvant Systems in vaccines: concepts, achievements and perspectives. Expert Rev Vaccines. 2007;6(5):723–739.
  • Gordon DM, McGovern TW, Krzych U, et al. Safety, immunogenicity, and efficacy of a recombinantly produced Plasmodium falciparum circumsporozoite protein-hepatitis B surface antigen subunit vaccine. J Infect Dis. 1995;171(6):1576–1585.
  • White MT, Bejon P, Olotu A, et al. A combined analysis of immunogenicity, antibody kinetics and vaccine efficacy from phase 2 trials of the RTS,S malaria vaccine. BMC Med. 2014;12:117.
  • Jepsen MP, Jogdand PS, Singh SK, et al. The malaria vaccine candidate GMZ2 elicits functional antibodies in individuals from malaria endemic and non-endemic areas. J Infect Dis. 2013.
  • Genton B, Al Yaman F, Anders R, et al. Safety and immunogenicity of a three-component blood-stage malaria vaccine in adults living in an endemic area of Papua New Guinea. Vaccine. 2000;18(23):2504–2511.
  • Lousada-Dietrich S, Jogdand PS, Jepsen S, et al. A synthetic TLR4 agonist formulated in an emulsion enhances humoral and Type 1 cellular immune responses against GMZ2–a GLURP-MSP3 fusion protein malaria vaccine candidate. Vaccine. 2011;29(17):3284–3292.
  • Agger EM, Rosenkrands I, Hansen J, et al. Cationic liposomes formulated with synthetic mycobacterial cordfactor (CAF01): a versatile adjuvant for vaccines with different immunological requirements. PLoS One. 2008;3(9):e3116.
  • Sheehy SH, Douglas AD, Draper SJ. Challenges of assessing the clinical efficacy of asexual blood-stage Plasmodium falciparum malaria vaccines. Hum Vaccin Immunother. 2013;9(9):1831–1840.
  • Viebig NK, D’Alessio F, Draper SJ, et al. Workshop report: malaria vaccine development in Europe–preparing for the future. Vaccine. 2015;33(46):6137–6144.
  • Tamborrini M, Stoffel SA, Westerfeld N, et al. Immunogenicity of a virosomally-formulated Plasmodium falciparum GLURP-MSP3 chimeric protein-based malaria vaccine candidate in comparison to adjuvanted formulations. Malar J. 2011;10:359.
  • Baldwin SL, Roeffen W, Singh SK, et al. Synthetic TLR4 agonists enhance functional antibodies and CD4+ T-cell responses against the Plasmodium falciparum GMZ2.6C multi-stage vaccine antigen. Vaccine. 2016;34(19):2207–2215.
  • Singh SK, Roeffen W, Andersen G, et al. A Plasmodium falciparum 48/45 single epitope R0.6C subunit protein elicits high levels of transmission blocking antibodies. Vaccine. 2015;33(16):1981–1986.

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