1,369
Views
0
CrossRef citations to date
0
Altmetric
Review

Plasmodium falciparum merozoite surface protein 1 as asexual blood stage malaria vaccine candidate

ORCID Icon, , , &
Pages 160-173 | Received 25 Sep 2023, Accepted 12 Dec 2023, Published online: 27 Dec 2023

References

  • World Health Organization. Malaria vaccine: WHO position paper - January 2016. Weekly Epidemiol Rec. 2016;91:33–52.
  • Organization, W.H. World malaria report 2021. (2021).
  • Hemingway J, Ranson H, Magill A, et al. Averting a malaria disaster: will insecticide resistance derail malaria control? Lancet. 2016;387:1785–1788.
  • Organization, W.H. World malaria report 2019. (2019).
  • Achan J, Serwanga A, Wanzira H, et al. Current malaria infection, previous malaria exposure, and clinical profiles and outcomes of COVID-19 in a setting of high malaria transmission: an exploratory cohort study in Uganda. Lancet Microbe. 2022;3:e62–e71.
  • Cervellati M, Esposito E, Sunde U, et al. Malaria risk and civil violence. Munich, Germany: CESifo; 2017.
  • Penny MA, Camponovo F, Chitnis N, et al. Future use-cases of vaccines in malaria control and elimination. Parasite Epidemiol Control. 2020;10:e00145.
  • Nussenzweig RS, Vanderberg J, Most H, et al. Protective immunity produced by the injection of x-irradiated sporozoites of plasmodium berghei. Nature. 1967;216:160–162.
  • Keating C. The history of the RTS,S/AS01 malaria vaccine trial. Lancet. 2020;395:1336–1337.
  • Crompton PD, Moebius J, Portugal S, et al. Malaria immunity in man and mosquito: insights into unsolved mysteries of a deadly infectious disease. Annu Rev Immunol. 2014;32:157–187.
  • Beeson JG, Kurtovic L, Valim C, et al. The RTS,S malaria vaccine: current impact and foundation for the future. Sci Transl Med. 2022;14:eabo6646.
  • Adepoju P. RTS,S malaria vaccine pilots in three African countries. Lancet. 2019;393:1685.
  • World Health Organization. World malaria report 2018. Geneva: World Health Organization; 2018.
  • Datoo MS, Natama MH, Somé A, et al. Efficacy of a low-dose candidate malaria vaccine, R21 in adjuvant matrix-M, with seasonal administration to children in Burkina Faso: a randomised controlled trial. Lancet. 2021;397:1809–1818.
  • Datoo MS, Natama HM, Somé A, et al. Efficacy and immunogenicity of R21/Matrix-M vaccine against clinical malaria after 2 years’ follow-up in children in Burkina Faso: a phase 1/2b randomised controlled trial. Lancet Infect Dis. 2022;22. doi: 10.1016/S1473-3099(22)00442-X
  • Epstein JE, Paolino KM, Richie TL, et al. Protection against Plasmodium falciparum malaria by PfSPZ vaccine. JCI Insight. 2017;2:e89154.
  • Richie TL, Church LWP, Murshedkar T, et al. Sporozoite immunization: innovative translational science to support the fight against malaria. Expert Rev Vaccines. 2023;22:964–1007.
  • Thera MA, Doumbo OK, Coulibaly D, et al. A field trial to assess a blood-stage malaria vaccine. N Engl J Med. 2011;365:1004–1013.
  • Genton B, Reed ZH. Asexual blood-stage malaria vaccine development: facing the challenges. Curr Opin Infect Dis. 2007;20:467–475.
  • Duffy PE, Patrick Gorres J. Malaria vaccines since 2000: progress, priorities, products. NPJ Vaccines. 2020;5:48.
  • Cai J, Chen S, Zhu F, et al. Whole-killed blood-stage vaccine: is it worthwhile to further develop it to control malaria? Front Microbiol. 2021;12:670775.
  • Dunachie SJ, Berthoud T, Keating SM, et al. MIG and the regulatory cytokines IL-10 and TGF-β1 correlate with malaria vaccine immunogenicity and efficacy. PLoS One. 2010;5:e12557.
  • Holder AA, Freeman RR. Immunization against blood-stage rodent malaria using purified parasite antigens. Nature. 1981;294:361–364.
  • Holder AA, Lockyer MJ, Odink KG, et al. Primary structure of the precursor to the three major surface antigens of Plasmodium falciparum merozoites. Nature. 1985;317:270–273.
  • Holder AA. The precursor to major merozoite surface antigens: structure and role in immunity. Prog Allergy. 1988;41:72–97.
  • Holder AA, Blackman MJ, Burghaus PA, et al. A malaria merozoite surface protein (MSP1)-structure, processing and function. Mem Inst Oswaldo Cruz. 1992;87 Suppl 3:37–42.
  • Koussis K, Withers-Martinez C, Yeoh S, et al. A multifunctional serine protease primes the malaria parasite for red blood cell invasion. EMBO J. 2009;28:725–735.
  • Harris PK, Yeoh S, Dluzewski AR, et al. Molecular identification of a malaria merozoite surface sheddase. PLoS Pathog. 2005;1:241–251.
  • Blackman MJ, Holder AA. Secondary processing of the Plasmodium falciparum merozoite surface protein-1 (MSP1) by a calcium-dependent membrane-bound serine protease: shedding of MSP133 as a noncovalently associated complex with other fragments of the MSP1. Mol Biochem Parasitol. 1992;50:307–315.
  • Child MA, Epp C, Bujard H, et al. Regulated maturation of malaria merozoite surface protein-1 is essential for parasite growth. Mol Microbiol. 2010;78:187–202.
  • Dluzewski AR, Ling IT, Hopkins JM, et al. Formation of the food vacuole in Plasmodium falciparum: a potential role for the 19 kDa fragment of merozoite surface protein 1 (MSP1(19)). PLoS One. 2008;3:e3085.
  • Trucco C, Fernandez-Reyes D, Howell S, et al. The merozoite surface protein 6 gene codes for a 36 kDa protein associated with the Plasmodium falciparum merozoite surface protein-1 complex. Mol Biochem Parasitol. 2001;112:91–101.
  • Stafford WHL, Günder B, Harris A, et al. A 22 kDa protein associated with the Plasmodium falciparum merozoite surface protein-1 complex. Mol Biochem Parasitol. 1996;80:159–169.
  • Pachebat JA, Ling IT, Grainger M, et al. The 22 kDa component of the protein complex on the surface of Plasmodium falciparum merozoites is derived from a larger precursor, merozoite surface protein 7. Mol Biochem Parasitol. 2001;117:83–89.
  • Chiu CY, Hodder AN, Lin CS, et al. Antibodies to the Plasmodium falciparum proteins MSPDBL1 and MSPDBL2 opsonize merozoites, inhibit parasite growth, and predict protection from clinical malaria. J Infect Dis. 2015;212:406–415.
  • Babiker HA, Creasey AM, Fenton B, et al. Genetic diversity of Plasmodium falciparum in a village in eastern Sudan. 1. Diversity of enzymes, 2D-PAGE proteins and antigens. Trans R Soc Trop Med Hyg. 1991;85:572–577.
  • Tanabe K, Mackay M, Goman M, et al. Allelic dimorphism in a surface antigen gene of the malaria parasite Plasmodium falciparum. J Mol Biol. 1987;195:273–287.
  • Takala S, Branch O, Escalante AA, et al. Evidence for intragenic recombination in Plasmodium falciparum: identification of a novel allele family in block 2 of merozoite surface protein-1: Asembo Bay Area Cohort Project XIV. Mol Biochem Parasitol. 2002;125:163–171.
  • Tanabe K, Sakihama N, Walliker D, et al. Allelic dimorphism-associated restriction of recombination in Plasmodium falciparum msp1. Gene. 2007;397:153–160.
  • Kiwanuka GN. Genetic diversity in Plasmodium falciparum merozoite surface protein 1 and 2 coding genes and its implications in malaria epidemiology: a review of published studies from 1997-2007. J Vector Borne Dis. 2009;46:1–12.
  • Levinson G, Gutman GA. Slipped-strand mispairing: a major mechanism for DNA sequence evolution. Mol Biol Evol. 1987;4:203–221.
  • Ferreira MU, Ribeiro WL, Tonon AP, et al. Sequence diversity and evolution of the malaria vaccine candidate merozoite surface protein-1 (MSP-1) of Plasmodium falciparum. Gene. 2003;304:65–75.
  • Gentz R, Certa U, Takacs B, et al. Major surface antigen p190 of Plasmodium falciparum: detection of common epitopes present in a variety of plasmodia isolates. Embo J. 1988;7:225–230.
  • Jongwutiwes S, Tanabe K, Nakazawa S, et al. Sequence variation in the tripeptide repeats and T cell epitopes in P190 (MSA-1) of Plasmodium falciparum from field isolates. Mol Biochem Parasitol. 1992;51:81–89.
  • Agonhossou R, Akoton R, Lagnika H, et al. P. falciparum msp1 and msp2 genetic diversity in P. falciparum single and mixed infection with P. malariae among the asymptomatic population in Southern Benin. Parasitol Int. 2022;89:102590.
  • Mwingira F, Nkwengulila G, Schoepflin S, et al. Plasmodium falciparum msp1, msp2 and glurp allele frequency and diversity in sub-Saharan Africa. Malar J. 2011;10:79.
  • Chen J-T, Li J, Zha G-C, et al. Genetic diversity and allele frequencies of Plasmodium falciparum msp1 and msp2 in parasite isolates from Bioko Island, Equatorial Guinea. Malar J. 2018;17:458.
  • Apinjoh TO, Tata RB, Anchang-Kimbi JK, et al. Plasmodium falciparum merozoite surface protein 1 block 2 gene polymorphism in field isolates along the slope of mount Cameroon: a cross – sectional study. BMC Infect Dis. 2015;15:309.
  • Somé AF, Bazié T, Zongo I, et al. Plasmodium falciparum msp1 and msp2 genetic diversity and allele frequencies in parasites isolated from symptomatic malaria patients in Bobo-Dioulasso, Burkina Faso. Parasit Vectors. 2018;11:323.
  • Miller LH, Roberts T, Shahabuddin M, et al. Analysis of sequence diversity in the Plasmodium falciparum merozoite surface protein-1 (MSP-1). Mol Biochem Parasitol. 1993;59:1–14.
  • Snounou G, Beck HP. The use of PCR genotyping in the assessment of recrudescence or reinfection after antimalarial drug treatment. Parasitol Today. 1998;14:462–467.
  • Cattamanchi A, Kyabayinze D, Hubbard A, et al. Distinguishing recrudescence from reinfection in a longitudinal antimalarial drug efficacy study: comparison of results based on genotyping of msp-1, msp-2, and glurp. Am J Trop Med Hyg. 2003;68:133–139.
  • Mohammed H, Mindaye T, Belayneh M, et al. Genetic diversity of Plasmodium falciparum isolates based on MSP-1 and MSP-2 genes from Kolla-Shele area, Arbaminch Zuria District, southwest Ethiopia. Malar J. 2015;14:73.
  • Otto TD, Böhme U, Sanders MJ, et al. Long read assemblies of geographically dispersed Plasmodium falciparum isolates reveal highly structured subtelomeres. Wellcome Open Res. 2018;3(52). doi: 10.12688/wellcomeopenres.14571.1
  • Moser KA, Dwivedi A, Stucke EM, et al. New Plasmodium falciparum genome assemblies from diverse endemic regions enables the comprehensive genomic and genetic characterization of clinical isolates. Am J Trop Med Hyg. 2017;97:511–511. AMER SOC TROP MED & HYGIENE 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
  • Tanabe K, Zollner G, Vaughan JA, et al. Plasmodium falciparum: genetic diversity and complexity of infections in an isolated village in western thailand. Parasitol Int. 2015;64:260–266.
  • Tanabe K, Mita T, Palacpac NMQ, et al. Within-population genetic diversity of Plasmodium falciparum vaccine candidate antigens reveals geographic distance from a Central sub-Saharan African origin. Vaccine. 2013;31:1334–1339.
  • White WL. Erratum to: why I hate the index finger. Hand (N Y). 2011;6:233.
  • Tanabe K, Sakihama N, Kaneko A. Stable SNPs in malaria antigen genes in isolated populations. Science. 2004;303:493.
  • Takala SL, Escalante AA, Branch OH, et al. Genetic diversity in the Block 2 region of the merozoite surface protein 1 (MSP-1) of Plasmodium falciparum: additional complexity and selection and convergence in fragment size polymorphism. Infect Genet Evol. 2006;6:417–424.
  • Rich SM, Ayala FJ. Population structure and recent evolution of Plasmodium falciparum. Proc Natl Acad Sci U S A. 2000;97:6994–7001.
  • Aponte JJ, Menendez C, Schellenberg D, et al. Age interactions in the development of naturally acquired immunity to Plasmodium falciparum and its clinical presentation. PLoS Med. 2007;4:e242.
  • Ellis RD, Wu Y, Martin LB, et al. Phase 1 study in malaria naïve adults of BSAM2/Alhydrogel®+CPG 7909, a blood stage vaccine against P. falciparum malaria. PLoS One. 2012;7:e46094.
  • Cohen S, Mc GI, Carrington S. Gamma-globulin and acquired immunity to human malaria. Nature. 1961;192:733–737.
  • Hviid L, Lopez-Perez M, Larsen MD, et al. No sweet deal: the antibody-mediated immune response to malaria. Trends Parasitol. 2022;38:428–434.
  • al-Yaman F, Genton B, Kramer KJ, et al. Assessment of the role of naturally acquired antibody levels to Plasmodium falciparum merozoite surface protein-1 in protecting Papua New Guinean children from malaria morbidity. Am J Trop Med Hyg. 1996;54:443–448.
  • Egan AF, Morris J, Barnish G, et al. Clinical immunity to Plasmodium falciparum malaria is associated with serum antibodies to the 19-kDa C-terminal fragment of the merozoite surface antigen, PfMSP-1. J Infect Dis. 1996;173:765–769.
  • Dodoo D, Theander TG, Kurtzhals JAL, et al. Levels of antibody to conserved parts of Plasmodium falciparum merozoite surface protein 1 in Ghanaian children are not associated with protection from clinical malaria. Infect Immun. 1999;67:2131–2137.
  • 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;76:759–766.
  • 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;76:2240–2248.
  • Bowman NM, Moormann AM, Bowman NM, et al. Longevity of genotype-specific immune responses to Plasmodium falciparum merozoite surface protein 1 in Kenyan children from regions of different malaria transmission intensity. Am J Trop Med Hyg. 2016;95:580–587.
  • Früh K, Doumbo O, Müller HM, et al. Human antibody response to the major merozoite surface antigen of Plasmodium falciparum is strain specific and short-lived. Infect Immun. 1991;59:1319–1324.
  • Muller HM, Früh K, von Brunn A, et al. Development of the human immune response against the major surface protein (gp190) of Plasmodium falciparum. Infect Immun. 1989;57:3765–3769.
  • Tolle R, Früh K, Doumbo O, et al. A prospective study of the association between the human humoral immune response to Plasmodium falciparum blood stage antigen gp190 and control of malarial infections. Infect Immun. 1993;61:40–47.
  • 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:e1000218.
  • Conway DJ, Cavanagh DR, Tanabe K, et al. A principal target of human immunity to malaria identified by molecular population genetic and immunological analyses. Nat Med. 2000;6:689–692.
  • Noranate N, Prugnolle F, Jouin H, et al. Population diversity and antibody selective pressure to Plasmodium falciparum MSP1 block2 locus in an African malaria-endemic setting. BMC Microbiol. 2009;9:219.
  • Cavanagh DR, Dodoo D, Hviid L, et al. Antibodies to the N-terminal block 2 of Plasmodium falciparum merozoite surface protein 1 are associated with protection against clinical malaria. Infect Immun. 2004;72:6492–6502.
  • Jaschke A, Coulibaly B, Remarque EJ, et al. Merozoite surface protein 1 from Plasmodium falciparum is a major target of opsonizing antibodies in individuals with acquired immunity against malaria. Clin Vaccine Immunol. 2017;24. DOI:10.1128/CVI.00155-17
  • Saul A, Lawrence G, Smillie A, et al. Human phase I vaccine trials of 3 recombinant asexual stage malaria antigens with Montanide ISA720 adjuvant. Vaccine. 1999;17:3145–3159.
  • 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;185:820–827.
  • Lawrence G, Cheng Q, Reed C, et al. Effect of vaccination with 3 recombinant asexual-stage malaria antigens on initial growth rates of Plasmodium falciparum in non-immune volunteers. Vaccine. 2000;18:1925–1931.
  • 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;18:2504–2511.
  • Blank A, Fürle K, Jäschke A, et al. Immunization with full-length Plasmodium falciparum merozoite surface protein 1 is safe and elicits functional cytophilic antibodies in a randomized first-in-human trial. NPJ Vaccines. 2020;5:10.
  • Nziza N, Tran TM, DeRiso EA, et al. Accumulation of neutrophil phagocytic antibody features tracks with naturally acquired immunity against malaria in children. J Infect Dis. 2023;228:759–768.
  • Perrin LH, Merkli B, Loche M, et al. Antimalarial immunity in Saimiri monkeys. Immunization with surface components of asexual blood stages. J Exp Med. 1984;160:441–451.
  • Siddiqui WA, Tam LQ, Kramer KJ, et al. Merozoite surface coat precursor protein completely protects Aotus monkeys against Plasmodium falciparum malaria. Proc Natl Acad Sci U S A. 1987;84:3014–3018.
  • Herrera S, Herrera MA, Perlaza BL, et al. Immunization of Aotus monkeys with Plasmodium falciparum blood-stage recombinant proteins. Proc Natl Acad Sci U S A. 1990;87:4017–4021.
  • Etlinger HM, Caspers P, Matile H, et al. Ability of recombinant or native proteins to protect monkeys against heterologous challenge with Plasmodium falciparum. Infect Immun. 1991;59:3498–3503.
  • Patarroyo ME, Romero P, Torres ML, et al. Induction of protective immunity against experimental infection with malaria using synthetic peptides. Nature. 1987;328:629–632.
  • Rodriguez R, Moreno A, Guzman F, et al. Studies in owl monkeys leading to the development of a synthetic vaccine against the asexual blood stages of Plasmodium falciparum. Am J Trop Med Hyg. 1990;43:339–354.
  • Moreno A, Patarroyo ME. Development of an asexual blood stage malaria vaccine. Blood. 1989;74:537–546.
  • Ruebush TKN, Campbell GH, Moreno A, et al. Immunization of owl monkeys with a combination of Plasmodium falciparum asexual blood-stage synthetic peptide antigens. Am J Trop Med Hyg. 1990;43:355–366.
  • Herrera S, Guerrero R, Clavijo C, et al. Failure of a synthetic vaccine to protect Aotus lemurinus against asexual blood stages of Plasmodium falciparum. Am J Trop Med Hyg. 1992;47:682–690.
  • Amador R, Moreno A, Murillo LA, et al. Safety and immunogenicity of the synthetic malaria vaccine SPf66 in a large field trial. J Infect Dis. 1992;166:139–144.
  • Amador R, Moreno A, Valero V, et al. The first field trials of the chemically synthesized malaria vaccine SPf66: safety, immunogenicity and protectivity. Vaccine. 1992;10:179–184.
  • Valero MV, Amador LR, Galindo C, et al. Vaccination with SPf66, a chemically synthesised vaccine, against Plasmodium falciparum malaria in Colombia. Lancet. 1993;341:705–710.
  • Sempértegui F, Estrella B, Moscoso J, et al. Safety, immunogenicity and protective effect of the SPf66 malaria synthetic vaccine against Plasmodium falciparum infection in a randomized double-blind placebo-controlled field trial in an endemic area of Ecuador. Vaccine. 1994;12:337–342.
  • Noya O, Berti YG, Noya BAD, et al. A population-based clinical trial with the SPf66 synthetic Plasmodium falciparum malaria vaccine in Venezuela. J Infect Dis. 1994;170:396–402.
  • Teuscher T, Armstrong Schellenberg JRM, Bastos de Azevedo I, et al. SPf66, a chemically synthesized subunit malaria vaccine, is safe and immunogenic in Tanzanians exposed to intense malaria transmission. Vaccine. 1994;12:328–336.
  • Alonso P, Smith T, Armstrong Schellenberg JRM, et al. Randomised trial of efficacy of SPf66 vaccine against Plasmodium falciparum malaria in children in southern Tanzania. Lancet. 1994;344:1175–1181.
  • Acosta C, Galindo CM, Schellenberg D, et al. Evaluation of the SPf66 vaccine for malaria control when delivered through the EPI scheme in Tanzania. Trop Med Int Health. 1999;4:368–376.
  • D’alessandro U, Leach A, Olaleye BO, et al. Efficacy trial of malaria vaccine SPf66 in Gambian infants. Lancet. 1995;346:462–467.
  • Nosten F, Luxemburger C, Kyle DE, et al. Randomised double-blind placebo-controlled trial of SPf66 malaria vaccine in children in northwestern Thailand. Lancet. 1996;348:701–707.
  • Urdaneta M, Struchiner CJ, Boulos M, et al. Evaluation of SPf66 malaria vaccine efficacy in Brazil. The American Journal of Tropical Medicine and Hygiene. 1998;58:378–385.
  • Kumar S, Yadava A, Keister DB, et al. Immunogenicity and in vivo efficacy of recombinant Plasmodium falciparum merozoite surface protein-1 in Aotus monkeys. Mol Med. 1995;1:325–332.
  • Darko CA, Angov E, Collins WE, et al. The clinical-grade 42-kilodalton fragment of merozoite surface protein 1 of Plasmodium falciparum strain FVO expressed in Escherichia coli protects Aotus nancymai against challenge with homologous erythrocytic-stage parasites. Infect Immun. 2005;73:287–297.
  • Singh S, Miura K, Zhou H, et al. 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. 2006;74:4573–4580.
  • Alaro JR, Partridge A, Miura K, et al. A chimeric Plasmodium falciparum merozoite surface protein vaccine induces high titers of parasite growth inhibitory antibodies. Infect Immun. 2013;81:3843–3854.
  • Burns JM Jr, Miura K, Sullivan J, et al. Immunogenicity of a chimeric Plasmodium falciparum merozoite surface protein vaccine in Aotus monkeys. Malar J. 2016;15:159.
  • Shi Q, Lynch MM, Romero M, et al. Enhanced protection against malaria by a chimeric merozoite surface protein vaccine. Infect Immun. 2007;75:1349–1358.
  • Alaro JR, Lynch MM, Burns JM Jr. Protective immune responses elicited by immunization with a chimeric blood-stage malaria vaccine persist but are not boosted by Plasmodium yoelii challenge infection. Vaccine. 2010;28:6876–6884.
  • Cowan GJ, Creasey AM, Dhansarnsombut K, et al. A malaria vaccine based on the polymorphic block 2 region of MSP-1 that elicits a broad serotype-spanning immune response. PLoS One. 2011;6:e26616.
  • Cavanagh DR, Kocken CHM, White JH, et al. Antibody responses to a novel Plasmodium falciparum merozoite surface protein vaccine correlate with protection against experimental malaria infection in Aotus monkeys. PLoS One. 2014;9:e83704.
  • Graves P, Gelband H. Vaccines for preventing malaria (SPf66). Cochrane Database Syst Rev. 2006;2006:Cd005966.
  • Daubenberger CA, Nickel B, Ciatto C, et al. Amino acid dimorphism and parasite immune evasion: cellular immune responses to a promiscuous epitope of Plasmodium falciparum merozoite surface protein 1 displaying dimorphic amino acid polymorphism are highly constrained. Eur J Immunol. 2002;32:3667–3677.
  • Pöltl-Frank F, Zurbriggen R, Helg A, et al. Use of reconstituted influenza virus virosomes as an immunopotentiating delivery system for a peptide-based vaccine. Clin Exp Immunol. 1999;117:496–503.
  • Keitel WA, Kester KE, Atmar RL, et al. Phase I trial of two recombinant vaccines containing the 19kd carboxy terminal fragment of Plasmodium falciparum merozoite surface protein 1 (msp-1(19)) and T helper epitopes of tetanus toxoid. Vaccine. 1999;18:531–539.
  • Stoute JA, Gombe J, Withers MR, et al. Phase 1 randomized double-blind safety and immunogenicity trial of Plasmodium falciparum malaria merozoite surface protein FMP1 vaccine, adjuvanted with AS02A, in adults in western Kenya. Vaccine. 2007;25:176–184.
  • Ockenhouse CF, Angov E, Kester KE, et al. Phase I safety and immunogenicity trial of FMP1/AS02A, a Plasmodium falciparum MSP-1 asexual blood stage vaccine. Vaccine. 2006;24:3009–3017.
  • Withers MR, McKinney D, Ogutu BR, et al. Safety and reactogenicity of an MSP-1 malaria vaccine candidate: a randomized phase Ib dose-escalation trial in Kenyan children. PLoS Clin Trials. 2006;1:e32.
  • Thera MA, Doumbo OK, Coulibaly D, et al. Safety and allele-specific immunogenicity of a malaria vaccine in Malian adults: results of a phase I randomized trial. PLoS Clin Trials. 2006;1:e34.
  • 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:e4708.
  • Malkin E, Long CA, Stowers AW, et al. Phase 1 study of two merozoite surface protein 1 (MSP1(42)) vaccines for Plasmodium falciparum malaria. PLoS Clin Trials. 2007;2:e12.
  • Ellis RD, Martin LB, Shaffer D, et al. Phase 1 trial of the Plasmodium falciparum blood stage vaccine MSP1(42)-C1/Alhydrogel with and without CPG 7909 in malaria naive adults. PLoS One. 2010;5:e8787.
  • Sheehy SH, Duncan CJ, Elias SC, et al. Phase Ia clinical evaluation of the Plasmodium falciparum blood-stage antigen MSP1 in ChAd63 and MVA vaccine vectors. Mol Ther. 2011;19:2269–2276.
  • Malkin E, Hu J, Li Z, et al. A phase 1 trial of PfCP2.9: an AMA1/MSP1 chimeric recombinant protein vaccine for Plasmodium falciparum malaria. Vaccine. 2008;26:6864–6873.
  • Sheehy SH, Duncan CJ, Elias SC, et al. ChAd63-MVA-vectored blood-stage malaria vaccines targeting MSP1 and AMA1: assessment of efficacy against mosquito bite challenge in humans. Mol Ther. 2012;20:2355–2368.
  • Biswas S, Choudhary P, Elias SC, et al. Assessment of humoral immune responses to blood-stage malaria antigens following ChAd63-MVA immunization, controlled human malaria infection and natural exposure. PLoS One. 2014;9:e107903.
  • Chitnis CE, Mukherjee P, Mehta S, et al. Phase I clinical trial of a recombinant blood stage vaccine candidate for Plasmodium falciparum malaria based on MSP1 and EBA175. PLoS One. 2015;10:e0117820.
  • Hall R, Hyde JE, Goman M, et al. Major surface antigen gene of a human malaria parasite cloned and expressed in bacteria. Nature. 1984;311:379–382.
  • Epp C, Kauth CW, Bujard H, et al. Expression and purification of Plasmodium falciparum MSP-1(42): a malaria vaccine candidate. J Chromatogr B Analyt Technol Biomed Life Sci. 2003;786:61–72.
  • Dijkman PM, Marzluf T, Zhang Y, et al. Structure of the merozoite surface protein 1 from Plasmodium falciparum. Sci Adv. 2021;7. doi: 10.1126/sciadv.abg0465
  • Kauth CW, Epp C, Bujard H, et al. The merozoite surface protein 1 complex of human malaria parasite Plasmodium falciparum: interactions and arrangements of subunits. J Biol Chem. 2003;278:22257–22264.
  • Joos C, Marrama L, Polson HEJ, et al. Clinical protection from falciparum malaria correlates with neutrophil respiratory bursts induced by merozoites opsonized with human serum antibodies. PLoS One. 2010;5:e9871.
  • Boyle MJ, Reiling L, Feng G, et al. Human antibodies fix complement to inhibit Plasmodium falciparum invasion of erythrocytes and are associated with protection against malaria. Immunity. 2015;42:580–590.
  • Reiling L, Boyle MJ, White MT, et al. Targets of complement-fixing antibodies in protective immunity against malaria in children. Nat Commun. 2019;10:610.
  • Hill DL, Eriksson EM, Li Wai Suen CSN, et al. Opsonising antibodies to P. falciparum merozoites associated with immunity to clinical malaria. PLoS One. 2013;8:e74627.
  • 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, Garcia-Senosiain A, Singh SK, et al. Cytophilic antibodies against key Plasmodium falciparum blood stage antigens contribute to protection against clinical malaria in a high transmission region of Eastern India. J Infect Dis. 2018;218:956–965.
  • Odera DO, Tuju J, Mwai K, et al. Antibodies targeting merozoites induce natural killer cell degranulation and interferon gamma secretion and are associated with immunity against malaria. Sci Transl Med. 2023;151:eabn5993. doi: 10.1126/scitranslmed.abn5993.
  • Feng G, Boyle MJ, Cross N, et al. Human immunization with a polymorphic malaria vaccine candidate induced antibodies to conserved epitopes that promote functional antibodies to multiple parasite strains. J Infect Dis. 2018;218:35–43.
  • Garcia-Senosiain A, Kana IH, Singh S, et al. Neutrophils dominate in opsonic phagocytosis of P. falciparum blood-stage merozoites and protect against febrile malaria. Commun Biol. 2021;4:984.
  • Nkumama IN, Odera D, Musasia F, et al. Breadth of Fc-mediated effector function delineates grades of clinical immunity following human malaria challenge. bioRxiv. 2022;2022:2010.2011.511755.
  • Rosenkranz M, Nkumama IN, Kraker S, et al. Full-length merozoite surface protein 1 of Plasmodium falciparum is a major target of protective immunity following controlled human malaria infections. medRxiv. 2022;2022.2010.2012.22280947.
  • Rosenkranz M, Fürle K, Hibbert J, et al. Multifunctional IgG/IgM antibodies and cellular cytotoxicity are elicited by the full-length MSP1 SumayaVac-1 malaria vaccine. NPJ Vaccines. 2023;8:112.
  • Marsh K, Kinyanjui S. Immune effector mechanisms in malaria. Parasite Immunol. 2006;28:51–60.
  • Conway DJ, Greenwood BM, McBride JS. Longitudinal study of Plasmodium falciparum polymorphic antigens in a malaria-endemic population. Infect Immun. 1992;60:1122–1127.
  • Riley EM, ALLEN SJ, Wheeler JG, et al. Naturally acquired cellular and humoral immune responses to the major merozoite surface antigen (Pf MSP1) of Plasmodium falciparum are associated with reduced malaria morbidity. Parasite Immunol. 1992;14:321–337.
  • Volz JC, Yap A, Sisquella X, et al. Essential role of the PfRh5/PfRipr/CyRPA complex during Plasmodium falciparum invasion of erythrocytes. Cell Host Microbe. 2016;20:60–71.
  • Douglas AD, Baldeviano G, Lucas C, et al. A PfRH5-based vaccine is efficacious against heterologous strain blood-stage Plasmodium falciparum infection in Aotus monkeys. Cell Host Microbe. 2015;17:130–139.
  • Payne RO, Silk SE, Elias SC, et al. Human vaccination against RH5 induces neutralizing antimalarial antibodies that inhibit RH5 invasion complex interactions. JCI Insight. 2017;2. doi: 10.1172/jci.insight.96381
  • Douglas AD, Baldeviano GC, Jin J, et al. A defined mechanistic correlate of protection against Plasmodium falciparum malaria in non-human primates. Nat Commun. 2019;10:1953.
  • Minassian AM, Silk SE, Barrett JR, et al. Reduced blood-stage malaria growth and immune correlates in humans following RH5 vaccination. Med (N Y). 2021;2:701–719.e719.
  • Tan J, Sack BK, Oyen D, et al. A public antibody lineage that potently inhibits malaria infection through dual binding to the circumsporozoite protein. Nat Med. 2018;24:401–407.
  • Kayentao K, Ongoiba A, Preston AC, et al. Safety and efficacy of a monoclonal antibody against malaria in Mali. N Engl J Med. 2022;387:1833–1842.
  • Chappel JA, Holder AA. Monoclonal antibodies that inhibit Plasmodium falciparum invasion in vitro recognise the first growth factor-like domain of merozoite surface protein-1. Mol Biochem Parasitol. 1993;60:303–311.
  • Uthaipibull C, Aufiero B, Syed SEH, et al. Inhibitory and blocking monoclonal antibody epitopes on merozoite surface protein 1 of the malaria parasite Plasmodium falciparum11Edited by J. A. Wells. J Mol Biol. 2001;307:1381–1394.
  • Locher CP, Tam LQ, Chang SP, et al. Plasmodium falciparum: gp195 tripeptide repeat-specific monoclonal antibody inhibits parasite growth in vitro. Exp Parasitol. 1996;84:74–83.
  • Patel PN, Dickey TH, Hopp CS, et al. Neutralizing and interfering human antibodies define the structural and mechanistic basis for antigenic diversion. Nat Commun. 2022;13:5888.
  • 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;291:7703–7715.