Skip to main content
PMC home page
Infection and Immunity logoLink to Infection and Immunity
. 1991 Oct;59(10):3498–3503. doi: 10.1128/iai.59.10.3498-3503.1991

Ability of recombinant or native proteins to protect monkeys against heterologous challenge with Plasmodium falciparum.

H M Etlinger 1, P Caspers 1, H Matile 1, H J Schoenfeld 1, D Stueber 1, B Takacs 1
PMCID: PMC258912  PMID: 1894356

Abstract

To circumvent problems associated with polymorphic vaccine candidates for Plasmodium falciparum malaria, we evaluated recombinant proteins representing sequences from relatively high conserved regions of the precursor to the major merozoite surface proteins, gp190, for their ability to protect Saimiri monkeys against malaria challenge. Recombinant proteins represented amino acid residues 147 to 321 (p190-1) or 147 to 321 and 1060 to 1195 (p190-3), and their efficacy was compared with that of native gp190 and its processed products. All antigens were derived from P. falciparum K1, a Thai isolate, while the challenge strain was Palo Alto (from Uganda, Africa), which contains, with the exception of the N-terminal 375 amino acids, which are almost identical to the K1 sequence, essentially the MAD-20 allelic form of gp190. By 12 days following challenge, each control monkey required drug treatment. Three monkeys injected with p190-3 required therapy, while one cleared the parasites without therapy. Two monkeys injected with p190-1 received therapy on day 14, while the remaining two cleared the parasites without therapy. Of four animals injected with native gp190, because of health reasons unrelated to malaria, one was not challenged with parasites and one was removed from the study 8 days after challenge when its parasitemia was 1.1% (parasitemias in control animals ranged from 4.3 to 9%); the remaining two cleared the parasites after maximum parasitemias of 0.45 and 0.53%. The highest levels of antiparasite antibody were produced by animals immunized with native gp190. There was a significant correlation between monkeys which did not require drug treatment and antiparasite antibody. These results may suggest that native gp190 and/or its processed products can provide excellent protection against heterologous challenge and that antibody is important for protection. The challenge for vaccine development is to identify the protective sequence(s).

Full text

PDF
3498

Images in this article

3499Image
on p.3499

Selected References

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

  1. Anders R. F. Multiple cross-reactivities amongst antigens of Plasmodium falciparum impair the development of protective immunity against malaria. Parasite Immunol. 1986 Nov;8(6):529–539. doi: 10.1111/j.1365-3024.1986.tb00867.x. [DOI] [PubMed] [Google Scholar]
  2. Burns J. M., Jr, Majarian W. R., Young J. F., Daly T. M., Long C. A. A protective monoclonal antibody recognizes an epitope in the carboxyl-terminal cysteine-rich domain in the precursor of the major merozoite surface antigen of the rodent malarial parasite, Plasmodium yoelii. J Immunol. 1989 Oct 15;143(8):2670–2676. [PubMed] [Google Scholar]
  3. Certa U., Rotmann D., Matile H., Reber-Liske R. A naturally occurring gene encoding the major surface antigen precursor p190 of Plasmodium falciparum lacks tripeptide repeats. EMBO J. 1987 Dec 20;6(13):4137–4142. doi: 10.1002/j.1460-2075.1987.tb02759.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chang S. P., Kramer K. J., Yamaga K. M., Kato A., Case S. E., Siddiqui W. A. Plasmodium falciparum: gene structure and hydropathy profile of the major merozoite surface antigen (gp195) of the Uganda-Palo Alto isolate. Exp Parasitol. 1988 Oct;67(1):1–11. doi: 10.1016/0014-4894(88)90002-1. [DOI] [PubMed] [Google Scholar]
  5. Etlinger H. M., Felix A. M., Gillessen D., Heimer E. P., Just M., Pink J. R., Sinigaglia F., Stürchler D., Takacs B., Trzeciak A. Assessment in humans of a synthetic peptide-based vaccine against the sporozoite stage of the human malaria parasite, Plasmodium falciparum. J Immunol. 1988 Jan 15;140(2):626–633. [PubMed] [Google Scholar]
  6. 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]
  7. Freeman R. R., Trejdosiewicz A. J., Cross G. A. Protective monoclonal antibodies recognising stage-specific merozoite antigens of a rodent malaria parasite. Nature. 1980 Mar 27;284(5754):366–368. doi: 10.1038/284366a0. [DOI] [PubMed] [Google Scholar]
  8. Gentz R., Certa U., Takacs B., Matile H., Döbeli H., Pink R., Mackay M., Bone N., Scaife J. G. Major surface antigen p190 of Plasmodium falciparum: detection of common epitopes present in a variety of plasmodia isolates. EMBO J. 1988 Jan;7(1):225–230. doi: 10.1002/j.1460-2075.1988.tb02803.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Goman M., Langsley G., Hyde J. E., Yankovsky N. K., Zolg J. W., Scaife J. G. The establishment of genomic DNA libraries for the human malaria parasite Plasmodium falciparum and identification of individual clones by hybridisation. Mol Biochem Parasitol. 1982 Jun;5(6):391–400. doi: 10.1016/0166-6851(82)90012-3. [DOI] [PubMed] [Google Scholar]
  10. Good M. F., Berzofsky J. A., Miller L. H. The T cell response to the malaria circumsporozoite protein: an immunological approach to vaccine development. Annu Rev Immunol. 1988;6:663–688. doi: 10.1146/annurev.iy.06.040188.003311. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. 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]
  13. Herrera S., Herrera M. A., Perlaza B. L., Burki Y., Caspers P., Döbeli H., Rotmann D., Certa U. Immunization of Aotus monkeys with Plasmodium falciparum blood-stage recombinant proteins. Proc Natl Acad Sci U S A. 1990 May;87(10):4017–4021. doi: 10.1073/pnas.87.10.4017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. Holder A. A., Freeman R. R., Nicholls S. C. Immunization against Plasmodium falciparum with recombinant polypeptides produced in Escherichia coli. Parasite Immunol. 1988 Nov;10(6):607–617. doi: 10.1111/j.1365-3024.1988.tb00248.x. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. 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]
  18. Howard R. F., Ardeshir F., Reese R. T. Conservation and antigenicity of N-terminal sequences of GP185 from different Plasmodium falciparum isolates. Gene. 1986;46(2-3):197–205. doi: 10.1016/0378-1119(86)90404-x. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. 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]
  21. Hui G. S., Siddiqui W. A. Serum from Pf195 protected Aotus monkeys inhibit Plasmodium falciparum growth in vitro. Exp Parasitol. 1987 Dec;64(3):519–522. doi: 10.1016/0014-4894(87)90068-3. [DOI] [PubMed] [Google Scholar]
  22. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Lyon J. A., Haynes J. D., Diggs C. L., Chulay J. D., Haidaris C. G., Pratt-Rossiter J. Monoclonal antibody characterization of the 195-kilodalton major surface glycoprotein of Plasmodium falciparum malaria schizonts and merozoites: identification of additional processed products and a serotype-restricted repetitive epitope. J Immunol. 1987 Feb 1;138(3):895–901. [PubMed] [Google Scholar]
  25. 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]
  26. 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]
  27. 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]
  28. 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]
  29. Siddiqui W. A., Tam L. Q., Kramer K. J., Hui G. S., Case S. E., Yamaga K. M., Chang S. P., Chan E. B., Kan S. C. Merozoite surface coat precursor protein completely protects Aotus monkeys against Plasmodium falciparum malaria. Proc Natl Acad Sci U S A. 1987 May;84(9):3014–3018. doi: 10.1073/pnas.84.9.3014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Takacs B., Staehli C. Activated macrophages and antibodies against the plant lectin, GSI-B4, recognize the same tumor-associated structure (TAS). J Immunol. 1987 Mar 15;138(6):1999–2007. [PubMed] [Google Scholar]
  31. Tanabe K., Mackay M., Goman M., Scaife J. G. Allelic dimorphism in a surface antigen gene of the malaria parasite Plasmodium falciparum. J Mol Biol. 1987 May 20;195(2):273–287. doi: 10.1016/0022-2836(87)90649-8. [DOI] [PubMed] [Google Scholar]
  32. 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]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES