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. 1987 May;84(9):3014–3018. doi: 10.1073/pnas.84.9.3014

Merozoite surface coat precursor protein completely protects Aotus monkeys against Plasmodium falciparum malaria.

W A Siddiqui, L Q Tam, K J Kramer, G S Hui, S E Case, K M Yamaga, S P Chang, E B Chan, S C Kan
PMCID: PMC304791  PMID: 3554251

Abstract

Groups of Aotus (owl) monkeys were immunized with either the Plasmodium falciparum merozoite surface-coat precursor protein and its processing fragments or a complex of high molecular mass rhoptry proteins and challenged with a lethal infection of the homologous P. falciparum Uganda Palo Alto (FUP) strain. No patent parasitemia could be detected on thick blood films of monkeys immunized with the merozoite surface antigens; however, only one of three monkeys immunized with the rhoptry proteins was partially protected, while two required drug therapy. The experiment clearly demonstrates that the merozoite surface-coat precursor protein can completely protect Aotus monkeys against a lethal infection of the human malaria parasite.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aikawa M., Miller L. H., Johnson J., Rabbege J. Erythrocyte entry by malarial parasites. A moving junction between erythrocyte and parasite. J Cell Biol. 1978 Apr;77(1):72–82. doi: 10.1083/jcb.77.1.72. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Aikawa M., Miller L. H., Rabbege J. R., Epstein N. Freeze-fracture study on the erythrocyte membrane during malarial parasite invasion. J Cell Biol. 1981 Oct;91(1):55–62. doi: 10.1083/jcb.91.1.55. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brown G. V., Culvenor J. G., Crewther P. E., Bianco A. E., Coppel R. L., Saint R. B., Stahl H. D., Kemp D. J., Anders R. F. Localization of the ring-infected erythrocyte surface antigen (RESA) of Plasmodium falciparum in merozoites and ring-infected erythrocytes. J Exp Med. 1985 Aug 1;162(2):774–779. doi: 10.1084/jem.162.2.774. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Campbell G. H., Miller L. H., Hudson D., Franco E. L., Andrysiak P. M. Monoclonal antibody characterization of Plasmodium falciparum antigens. Am J Trop Med Hyg. 1984 Nov;33(6):1051–1054. doi: 10.4269/ajtmh.1984.33.1051. [DOI] [PubMed] [Google Scholar]
  5. Cheung A., Shaw A. R., Leban J., Perrin L. H. Cloning and expression in Escherichia coli of a surface antigen of Plasmodium falciparum merozoites. EMBO J. 1985 Apr;4(4):1007–1011. doi: 10.1002/j.1460-2075.1985.tb03731.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Collins W. E., Anders R. F., Pappaioanou M., Campbell G. H., Brown G. V., Kemp D. J., Coppel R. L., Skinner J. C., Andrysiak P. M., Favaloro J. M. Immunization of Aotus monkeys with recombinant proteins of an erythrocyte surface antigen of Plasmodium falciparum. Nature. 1986 Sep 18;323(6085):259–262. doi: 10.1038/323259a0. [DOI] [PubMed] [Google Scholar]
  7. Coppel R. L., Cowman A. F., Anders R. F., Bianco A. E., Saint R. B., Lingelbach K. R., Kemp D. J., Brown G. V. Immune sera recognize on erythrocytes Plasmodium falciparum antigen composed of repeated amino acid sequences. 1984 Aug 30-Sep 5Nature. 310(5980):789–792. doi: 10.1038/310789a0. [DOI] [PubMed] [Google Scholar]
  8. Freeman R. R., Holder A. A. 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. 1983 Nov 1;158(5):1647–1653. doi: 10.1084/jem.158.5.1647. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hall R., Hyde J. E., Goman M., Simmons D. L., Hope I. A., Mackay M., Scaife J., Merkli B., Richle R., Stocker J. Major surface antigen gene of a human malaria parasite cloned and expressed in bacteria. 1984 Sep 27-Oct 3Nature. 311(5984):379–382. doi: 10.1038/311379a0. [DOI] [PubMed] [Google Scholar]
  10. Hall R., Osland A., Hyde J. E., Simmons D. L., Hope I. A., Scaife J. G. Processing, polymorphism, and biological significance of P190, a major surface antigen of the erythrocytic forms of Plasmodium falciparum. Mol Biochem Parasitol. 1984 Apr;11:61–80. doi: 10.1016/0166-6851(84)90055-0. [DOI] [PubMed] [Google Scholar]
  11. Holder A. A., Freeman R. R. Biosynthesis and processing of a Plasmodium falciparum schizont antigen recognized by immune serum and a monoclonal antibody. J Exp Med. 1982 Nov 1;156(5):1528–1538. doi: 10.1084/jem.156.5.1528. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Holder A. A., Freeman R. R. Immunization against blood-stage rodent malaria using purified parasite antigens. Nature. 1981 Nov 26;294(5839):361–364. doi: 10.1038/294361a0. [DOI] [PubMed] [Google Scholar]
  13. Holder A. A., Freeman R. R. The three major antigens on the surface of Plasmodium falciparum merozoites are derived from a single high molecular weight precursor. J Exp Med. 1984 Aug 1;160(2):624–629. doi: 10.1084/jem.160.2.624. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Holder A. A., Freeman R. R., Uni S., Aikawa M. Isolation of a Plasmodium falciparum rhoptry protein. Mol Biochem Parasitol. 1985 Mar;14(3):293–303. doi: 10.1016/0166-6851(85)90057-x. [DOI] [PubMed] [Google Scholar]
  15. Holder A. A., Lockyer M. J., Odink K. G., Sandhu J. S., Riveros-Moreno V., Nicholls S. C., Hillman Y., Davey L. S., Tizard M. L., Schwarz R. T. Primary structure of the precursor to the three major surface antigens of Plasmodium falciparum merozoites. Nature. 1985 Sep 19;317(6034):270–273. doi: 10.1038/317270a0. [DOI] [PubMed] [Google Scholar]
  16. Howard R. F., Stanley H. A., Campbell G. H., Reese R. T. Proteins responsible for a punctate fluorescence pattern in Plasmodium falciparum merozoites. Am J Trop Med Hyg. 1984 Nov;33(6):1055–1059. doi: 10.4269/ajtmh.1984.33.1055. [DOI] [PubMed] [Google Scholar]
  17. Howard R. J., Lyon J. A., Diggs C. L., Haynes J. D., Leech J. H., Barnwell J. W., Aley S. B., Aikawa M., Miller L. H. Localization of the major Plasmodium falciparum glycoprotein on the surface of mature intraerythrocytic trophozoites and schizonts. Mol Biochem Parasitol. 1984 Apr;11:349–362. doi: 10.1016/0166-6851(84)90078-1. [DOI] [PubMed] [Google Scholar]
  18. Howard R. J., McBride J. S., Aley S. B., Marsh K. Antigenic diversity and size diversity of P. falciparum antigens in isolates from Gambian patients. II. the schizont surface glycoprotein of molecular weight approximately 200 000. Parasite Immunol. 1986 Jan;8(1):57–68. doi: 10.1111/j.1365-3024.1986.tb00833.x. [DOI] [PubMed] [Google Scholar]
  19. Lyon J. A., Geller R. H., Haynes J. D., Chulay J. D., Weber J. L. Epitope map and processing scheme for the 195,000-dalton surface glycoprotein of Plasmodium falciparum merozoites deduced from cloned overlapping segments of the gene. Proc Natl Acad Sci U S A. 1986 May;83(9):2989–2993. doi: 10.1073/pnas.83.9.2989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lyon J. A., Haynes J. D. Plasmodium falciparum antigens synthesized by schizonts and stabilized at the merozoite surface when schizonts mature in the presence of protease inhibitors. J Immunol. 1986 Mar 15;136(6):2245–2251. [PubMed] [Google Scholar]
  21. Mackay M., Goman M., Bone N., Hyde J. E., Scaife J., Certa U., Stunnenberg H., Bujard H. Polymorphism of the precursor for the major surface antigens of Plasmodium falciparum merozoites: studies at the genetic level. EMBO J. 1985 Dec 30;4(13B):3823–3829. doi: 10.1002/j.1460-2075.1985.tb04154.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. McBride J. S., Newbold C. I., Anand R. Polymorphism of a high molecular weight schizont antigen of the human malaria parasite Plasmodium falciparum. J Exp Med. 1985 Jan 1;161(1):160–180. doi: 10.1084/jem.161.1.160. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Perlmann H., Berzins K., Wahlgren M., Carlsson J., Björkman A., Patarroyo M. E., Perlmann P. Antibodies in malarial sera to parasite antigens in the membrane of erythrocytes infected with early asexual stages of Plasmodium falciparum. J Exp Med. 1984 Jun 1;159(6):1686–1704. doi: 10.1084/jem.159.6.1686. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Perrin L. H., Merkli B., Gabra M. S., Stocker J. W., Chizzolini C., Richle R. Immunization with a Plasmodium falciparum merozoite surface antigen induces a partial immunity in monkeys. J Clin Invest. 1985 May;75(5):1718–1721. doi: 10.1172/JCI111881. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Perrin L. H., Merkli B., Loche M., Chizzolini C., Smart J., Richle R. Antimalarial immunity in Saimiri monkeys. Immunization with surface components of asexual blood stages. J Exp Med. 1984 Aug 1;160(2):441–451. doi: 10.1084/jem.160.2.441. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Pirson P. J., Perkins M. E. Characterization with monoclonal antibodies of a surface antigen of Plasmodium falciparum merozoites. J Immunol. 1985 Mar;134(3):1946–1951. [PubMed] [Google Scholar]
  27. Schofield L., Bushell G. R., Cooper J. A., Saul A. J., Upcroft J. A., Kidson C. A rhoptry antigen of Plasmodium falciparum contains conserved and variable epitopes recognized by inhibitory monoclonal antibodies. Mol Biochem Parasitol. 1986 Feb;18(2):183–195. doi: 10.1016/0166-6851(86)90037-x. [DOI] [PubMed] [Google Scholar]
  28. Schwarz R. T., Riveros-Moreno V., Lockyer M. J., Nicholls S. C., Davey L. S., Hillman Y., Sandhu J. S., Freeman R. R., Holder A. A. Structural diversity of the major surface antigen of Plasmodium falciparum merozoites. Mol Cell Biol. 1986 Mar;6(3):964–968. doi: 10.1128/mcb.6.3.964. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Siddiqui W. A. An effective immunization of experimental monkeys against a human malaria parasite, Plasmodium falciparum. Science. 1977 Jul 22;197(4301):388–389. doi: 10.1126/science.406671. [DOI] [PubMed] [Google Scholar]
  30. Siddiqui W. A., Kan S. C., Kramer K., Case S., Palmer K., Niblack J. F. Use of a synthetic adjuvant in an effective vaccination of monkeys against malaria. Nature. 1981 Jan 1;289(5793):64–66. doi: 10.1038/289064a0. [DOI] [PubMed] [Google Scholar]
  31. Siddiqui W. A., Tam L. Q., Kan S. C., Kramer K. J., Case S. E., Palmer K. L., Yamaga K. M., Hui G. S. Induction of protective immunity to monoclonal-antibody-defined Plasmodium falciparum antigens requires strong adjuvant in Aotus monkeys. Infect Immun. 1986 Apr;52(1):314–318. doi: 10.1128/iai.52.1.314-318.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Siddiqui W. A., Taylor D. W., Kan S. C., Kramer K., Richmond-Crum S. M., Kotani S., Shiba T., Kusumoto S. Vaccination of experimental monkeys against Plasmodium falciparum: a possible safe adjuvant. Science. 1978 Sep 29;201(4362):1237–1239. doi: 10.1126/science.99814. [DOI] [PubMed] [Google Scholar]
  33. Trager W., Jensen J. B. Human malaria parasites in continuous culture. Science. 1976 Aug 20;193(4254):673–675. doi: 10.1126/science.781840. [DOI] [PubMed] [Google Scholar]
  34. Weber J. L., Leininger W. M., Lyon J. A. Variation in the gene encoding a major merozoite surface antigen of the human malaria parasite Plasmodium falciparum. Nucleic Acids Res. 1986 Apr 25;14(8):3311–3323. doi: 10.1093/nar/14.8.3311. [DOI] [PMC free article] [PubMed] [Google Scholar]

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