ANTIGENICITY, IMMUNOGENICITY, AND PROTECTIVE EFFICACY OF PLASMODIUM VIVAX MSP1 PV200L: A POTENTIAL MALARIA VACCINE SUBUNIT

AUGUSTO VALDERRAMA-AGUIRRE Instituto de Inmunología and Fundacion Centro de Primates, Universidad del Valle, Cali, Colombia; Malaria Vaccine and Drug Development Center, Cali, Colombia

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GUSTAVO QUINTERO Instituto de Inmunología and Fundacion Centro de Primates, Universidad del Valle, Cali, Colombia; Malaria Vaccine and Drug Development Center, Cali, Colombia

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ANDRÉS GÓMEZ Instituto de Inmunología and Fundacion Centro de Primates, Universidad del Valle, Cali, Colombia; Malaria Vaccine and Drug Development Center, Cali, Colombia

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ALEJANDRO CASTELLANOS Instituto de Inmunología and Fundacion Centro de Primates, Universidad del Valle, Cali, Colombia; Malaria Vaccine and Drug Development Center, Cali, Colombia

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YOBANA PÉREZ Instituto de Inmunología and Fundacion Centro de Primates, Universidad del Valle, Cali, Colombia; Malaria Vaccine and Drug Development Center, Cali, Colombia

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FABIÁN MÉNDEZ Instituto de Inmunología and Fundacion Centro de Primates, Universidad del Valle, Cali, Colombia; Malaria Vaccine and Drug Development Center, Cali, Colombia

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MYRIAM ARÉVALO-HERRERA Instituto de Inmunología and Fundacion Centro de Primates, Universidad del Valle, Cali, Colombia; Malaria Vaccine and Drug Development Center, Cali, Colombia

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SÓCRATES HERRERA Instituto de Inmunología and Fundacion Centro de Primates, Universidad del Valle, Cali, Colombia; Malaria Vaccine and Drug Development Center, Cali, Colombia

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The merozoite surface protein 1 (MSP-1) is expressed in all Plasmodium species and is considered a major malaria vaccine candidate. We found that MSP-1 from Plasmodium vivax (PvMSP-1) contains a region of significant sequence homology with the 190L subunit vaccine derived from the P. falciparum MSP-1. The fragment, termed Pv200L, was expressed as a recombinant protein in Escherichia coli (rPv200L) and used to asses its immunologic relevance as a vaccine target. A cross-sectional, seroepidemiologic study conducted in Buenaventura, Colombia showed that 52.2% (95% confidence interval [CI] = 39.8–64.3) of individuals previously exposed to P. vivax and 72.8% (95% CI = 61.8–82.1) of P. vivax–infected patients had IgG antibodies to rPv200L. Immunization of BALB/c mice and Aotus monkeys induced IgG antibodies (titer > 106) that cross-reacted with P. vivax parasites. Immunized monkeys displayed partial protection against a challenge with P. vivax blood stages. Our results suggest that Pv200L is a new malaria vaccine subunit and deserves further testing.

Author Notes

Reprint requests: Sócrates Herrera, Malaria Vaccine and Drug Development Center, Carrera 35 # 4A-53, AA 26020, Cali, Colombia.
  • 1

    Mendis K, Sina BJ, Marchesini P, Carter R, 2001. The neglected burden of Plasmodium vivax malaria. Am J Trop Med Hyg 64 :97–106.

  • 2

    Arévalo-Herrera M, Herrera S, 2001. Plasmodium vivax malaria vaccine development. Mol Immunol 38 :443–455.

  • 3

    Freeman RR, Holder AA, 1983. Surface antigens of malaria merozoites. A high molecular weight precursor is processed to an 83,000 mol wt form expressed on the surface of Plasmodium falciparum merozoites. J Exp Med 158 :1647–1653.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Holder AA, Blackman MJ, Burghaus PA, Chappel JA, Ling IT, McCallum-Deighton N, Shai S, 1992. A malaria merozoite surface protein (MSP1)-structure, processing and function. Mem Inst Oswaldo Cruz 87 :37–42.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Blackman MJ, Scott-Finnigan TJ, Shai S, Holder AA, 1994. Antibodies inhibit the protease-mediated processing of a malaria merozoite surface protein. J Exp Med 180 :389–393.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Chappel JA, Holder AA, 1993. Monoclonal antibodies that inhibit Plasmodium falciparum invasion in vitro recognise the first growth factor-like domain of merozoite surface protein-1. Mol Biochem Parasitol 60 :303–311.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Uthaipibull C, Aufiero B, Syed SE, Hansen B, Guevara Patino JA, Angov E, Ling IT, Fegeding K, Morgan WD, Ockenhouse C, Birdsall B, Feeney J, Lyon JA, Holder AA, 2001. Inhibitory and blocking monoclonal antibody epitopes on merozoite surface protein 1 of the malaria parasite Plasmodium falciparum. J Mol Biol 307 :1381–1394.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Etlinger HM, Caspers P, Matile H, Schoenfeld HJ, Stueber D, Takacs B, 1991. Ability of recombinant or native proteins to protect monkeys against heterologous challenge with Plasmodium falciparum. Infect Immun 59 :3498–3503.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9

    Herrera MA, Rosero F, Herrera S, Caspers P, Rotmann D, Sinigaglia F, Certa U, 1992. Protection against malaria in Aotus monkeys immunized with a recombinant blood-stage antigen fused to a universal T-cell epitope: correlation of serum gamma interferon levels with protection. Infect Immun 60 :154–158.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Egan AF, Blackman MJ, Kaslow DC, 2000. Vaccine efficacy of recombinant Plasmodium falciparum merozoite surface protein 1 in malaria-naive, -exposed, and/or -rechallenged Aotus vociferans monkeys. Infect Immun 68 :1418–1427.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Yang C, Collins WE, Sullivan JS, Kaslow DC, Xiao L, Lal AA, 1999. Partial protection against Plasmodium vivax blood-stage infection in Saimiri monkeys by immunization with a recombinant C-terminal fragment of merozoite surface protein 1 in block copolymer adjuvant. Infect Immun 67 :342–349.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Sierra AY, Barrero CA, Rodriguez R, Silva Y, Moncada C, Vanegas M, Patarroyo MA, 2003. Splenectomised and spleen intact Aotus monkeys’ immune response to Plasmodium vivax MSP-1 protein fragments and their high activity binding peptides. Vaccine 21 :4133–4144.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Perera KL, Handunnetti SM, Holm I, Longacre S, Mendis K, 1998. Baculovirus merozoite surface protein 1 C-terminal recombinant antigens are highly protective in a natural primate model for human Plasmodium vivax malaria. Infect Immun 66 :1500–1506.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Dutta S, Ware LA, Barbosa A, Ockenhouse CF, Lanar DE, 2001. Purification, characterization, and immunogenicity of a disulfide cross-linked Plasmodium vivax vaccine candidate antigen, merozoite surface protein 1, expressed in Escherichia coli. Infect Immun 69 :5464–5470.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Collins WE, Kaslow DC, Sullivan JS, Morris CL, Galland GG, Yang C, Saekhou AM, Xiao L, Lal AA, 1999. Testing the efficacy of a recombinant merozoite surface protein (MSP-1(19) of Plasmodium vivax in Saimiri boliviensis monkeys. Am J Trop Med Hyg 60 :350–356.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Genton B, Betuela I, Felger I, Al-Yaman F, Anders RF, Saul A, Rare L, Baisor M, Lorry K, Brown GV, Pye D, Irving DO, Smith TA, Beck HP, Alpers MP, 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 :820–827.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    Genton B, Al-Yaman F, Anders R, Saul A, Brown G, Pye D, Irving DO, Briggs WR, Mai A, Ginny M, Adiguma T, Rare L, Giddy A, Reber-Liske R, Stuerchler D, Alpers MP, 2000. Safety and immunogenicity of a three-component blood-stage malaria vaccine in adults living in an endemic area of Papua New Guinea. Vaccine 18 :2504–2511.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Altschul SF, Madden TL, Schaffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ, 1997. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25 :3389–3402.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    Thompson JD, Gibson TJ, Plewniak F, Jeanmougin F, Higgins DG, 1997. The CLUSTAL_X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Res 25 :4876–4882.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    Qiagen, 2001. The QIAexpressionist. A Handbook for High-Level Expression and Purification of 6xHis-Tagged Proteins. Fifth Edition. Valencia, CA: Qiagen.

    • PubMed
    • Export Citation
  • 21

    Berzofsky RN, 1995. Endotoxin detection in pharmaceuticals and medical devices with Kinetic-QCL, a kinetic-quantitative chromogenic Limulus amebocyte lysate assay. Altex 12 :93–97.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22

    Gonzalez JM, Olano V, Vergara J, Arevalo-Herrera M, Carrasquilla G, Herrera S, Lopez JA, 1997. Unstable, low-level transmission of malaria on the Colombian Pacific coast. Ann Trop Med Parasitol 91 :349–358.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    PET, 2001. Informe Comportamiento Epidemiológico de Malaria. Buenaventura (V): Programa de Enfermedades Tropicales, Buena Ventura, Valle, Columbia.

    • PubMed
    • Export Citation
  • 24

    Shute PG, Maryon M, 1963. An improved technique for staining malaria parasites with Giemsa stain. Arch Roum Pathol Exp Microbiol 22 :887–894.

  • 25

    Perlaza BL, Zapata C, Valencia AZ, Hurtado S, Quintero G, Sauzet JP, Brahimi K, Blanc C, Arevalo-Herrera M, Druilhe P, Herrera S, 2003. Immunogenicity and protective efficacy of Plasmodium falciparum liver-stage Ag-3 in Aotus lemurinus griseimembra monkeys. Eur J Immunol 33 :1321–1327.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26

    Perraut R, Guillotte M, Drame I, Diouf B, Molez JF, Tall A, Trape JF, Mercereau-Puijalon O, Spiegel A, Garraud O, 2002. Evaluation of anti-Plasmodium falciparum antibodies in Senegalese adults using different types of crude extracts from various strains of parasite. Microbes Infect 4 :31–35.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27

    Epp C, Kauth CW, Bujard H, Lutz R, 2003. Expression and purification of Plasmodium falciparum MSP-1(42): A malaria vaccine candidate. J Chromatogr B Analyt Technol Biomed Life Sci 786 :61–72.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28

    Golenda CF, Li J, Rosenberg R, 1997. Continuous in vitro propagation of the malaria parasite Plasmodium vivax. Proc Natl Acad Sci USA 94 :6786–6791.

  • 29

    Rodriguez LE, Urquiza M, Ocampo M, Curtidor H, Suarez J, Garcia J, Vera R, Puentes A, Lopez R, Pinto M, Rivera Z, Patarroyo ME, 2002. Plasmodium vivax MSP-1 peptides have high specific binding activity to human reticulocytes. Vaccine 20 :1331–1339.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30

    Putaporntip C, Jongwutiwes S, Sakihama N, Ferreira MU, Kho WG, Kaneko A, Kanbara H, Hattori T, Tanabe K, 2002. Mosaic organization and heterogeneity in frequency of allelic recombination of the Plasmodium vivax merozoite surface protein-1 locus. Proc Natl Acad Sci USA 99 :16348–16353.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31

    Soares IS, Levitus G, Souza JM, Del Portillo HA, Rodrigues MM, 1997. Acquired immune responses to the N- and C-terminal regions of Plasmodium vivax merozoite surface protein 1 in individuals exposed to malaria. Infect Immun 65 :1606–1614.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32

    Soares IS, Oliveira SG, Souza JM, Rodrigues MM, 1999. Antibody response to the N and C-terminal regions of the Plasmodium vivax merozoite surface protein 1 in individuals living in an area of exclusive transmission of P. vivax malaria in the north of Brazil. Acta Trop 72 :13–24.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33

    Urban BC, Mwangi T, Ross A, Kinyanjui S, Mosobo M, Kai O, Lowe B, Marsh K, Roberts DJ, 2001. Peripheral blood dendritic cells in children with acute Plasmodium falciparum malaria. Blood 98 :2859–2861.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34

    Urban BC, Ferguson DJ, Pain A, Willcox N, Plebanski M, Austyn JM, Roberts DJ, 1999. Plasmodium falciparum-infected erythrocytes modulate the maturation of dendritic cells. Nature 400 :73–77.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35

    Wipasa J, Xu H, Stowers A, Good MF, 2001. Apoptotic deletion of Th cells specific for the 19-kDa carboxyl-terminal fragment of merozoite surface protein 1 during malaria infection. J Immunol 167 :3903–3909.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36

    Herrera MA, Rosero F, Herrera S, Caspers P, Rotmann D, Sinigaglia F, Certa U, 1991. Protection against malaria in Aotus monkeys immunized with a recombinant blood stage antigen fused to a “universal” T-cell epitope: correlation of γ-IFN serum levels with protection. Infect Immun 60 :154–158.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 37

    Herrera S, Rudin W, Herrera M, Clavijo P, Mancilla L, de Plata C, Matile H, Certa U, 1993. A conserved region of the MSP-1 surface protein of Plasmodium falciparum contains a recognition sequence for erythrocyte spectrin. EMBO J 12 :1607–1614.

    • PubMed
    • Search Google Scholar
    • Export Citation
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