Abstract
The Plasmodium falciparum gene encoding erythrocyte binding antigen-175 (EBA-175), a putative receptor for red cell invasion (Camus, D., and T. J. Hadley. 1985. Science (Wash. DC). 230:553-556.), has been isolated and characterized. DNA sequencing demonstrated a single open reading frame encoding a translation product of 1,435 amino acid residues. Peptides corresponding to regions on the deduced amino acid sequence predicted to be B cell epitopes were assessed for immunogenicity. Immunization of mice and rabbits with EBA-peptide 4, a synthetic peptide encompassing amino acid residues 1,062-1,103, produced antibodies that recognized P. falciparum merozoites in an indirect fluorescent antibody assay. When compared to sera from rabbits immunized with the same adjuvant and carrier protein, sera from rabbits immunized with EBA-peptide 4 inhibited merozoite invasion of erythrocytes in vitro by 80% at a 1:5 dilution. Furthermore, these sera inhibited the binding of purified, authentic EBA-175 to erythrocytes, suggesting that their activity in inhibiting merozoite invasion of erythrocytes is mediated by blocking the binding of EBA-175 to erythrocytes. Since the nucleotide sequence of EBA-peptide 4 is conserved among seven strains of P. falciparum from throughout the world (Sim, B. K. L. 1990. Mol. Biochem. Parasitol. 41:293-296.), these data identify a region of the protein that should be a focus of vaccine development efforts.
Full Text
The Full Text of this article is available as a PDF (1.4 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Blake M. S., Johnston K. H., Russell-Jones G. J., Gotschlich E. C. A rapid, sensitive method for detection of alkaline phosphatase-conjugated anti-antibody on Western blots. Anal Biochem. 1984 Jan;136(1):175–179. doi: 10.1016/0003-2697(84)90320-8. [DOI] [PubMed] [Google Scholar]
- Camus D., Hadley T. J. A Plasmodium falciparum antigen that binds to host erythrocytes and merozoites. Science. 1985 Nov 1;230(4725):553–556. doi: 10.1126/science.3901257. [DOI] [PubMed] [Google Scholar]
- Chulay J. D., Haynes J. D., Diggs C. L. Inhibition of in vitro growth of Plasmodium falciparum by immune serum from monkeys. J Infect Dis. 1981 Sep;144(3):270–278. doi: 10.1093/infdis/144.3.270. [DOI] [PubMed] [Google Scholar]
- Devereux J., Haeberli P., Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. doi: 10.1093/nar/12.1part1.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hadley T. J., Klotz F. W., Pasvol G., Haynes J. D., McGinniss M. H., Okubo Y., Miller L. H. Falciparum malaria parasites invade erythrocytes that lack glycophorin A and B (MkMk). Strain differences indicate receptor heterogeneity and two pathways for invasion. J Clin Invest. 1987 Oct;80(4):1190–1193. doi: 10.1172/JCI113178. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hadley T. J., Miller L. H. Invasion of erythrocytes by malaria parasites: erythrocyte ligands and parasite receptors. Prog Allergy. 1988;41:49–71. [PubMed] [Google Scholar]
- Harn D. A., Mitsuyama M., David J. R. Schistosoma mansoni. Anti-egg monoclonal antibodies protect against cercarial challenge in vivo. J Exp Med. 1984 May 1;159(5):1371–1387. doi: 10.1084/jem.159.5.1371. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Haynes J. D., Dalton J. P., Klotz F. W., McGinniss M. H., Hadley T. J., Hudson D. E., Miller L. H. Receptor-like specificity of a Plasmodium knowlesi malarial protein that binds to Duffy antigen ligands on erythrocytes. J Exp Med. 1988 Jun 1;167(6):1873–1881. doi: 10.1084/jem.167.6.1873. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hopp T. P., Woods K. R. Prediction of protein antigenic determinants from amino acid sequences. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3824–3828. doi: 10.1073/pnas.78.6.3824. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jungery M., Boyle D., Patel T., Pasvol G., Weatherall D. J. Lectin-like polypeptides of P. falciparum bind to red cell sialoglycoproteins. Nature. 1983 Feb 24;301(5902):704–705. doi: 10.1038/301704a0. [DOI] [PubMed] [Google Scholar]
- Klotz F. W., Hadley T. J., Aikawa M., Leech J., Howard R. J., Miller L. H. A 60-kDa Plasmodium falciparum protein at the moving junction formed between merozoite and erythrocyte during invasion. Mol Biochem Parasitol. 1989 Sep;36(2):177–185. doi: 10.1016/0166-6851(89)90190-4. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Miller L. H., Haynes J. D., McAuliffe F. M., Shiroishi T., Durocher J. R., McGinniss M. H. Evidence for differences in erythrocyte surface receptors for the malarial parasites, Plasmodium falciparum and Plasmodium knowlesi. J Exp Med. 1977 Jul 1;146(1):277–281. doi: 10.1084/jem.146.1.277. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Miller L. H., Howard R. J., Carter R., Good M. F., Nussenzweig V., Nussenzweig R. S. Research toward malaria vaccines. Science. 1986 Dec 12;234(4782):1349–1356. doi: 10.1126/science.2431481. [DOI] [PubMed] [Google Scholar]
- Okoye V. C., Bennett V. Plasmodium falciparum malaria: band 3 as a possible receptor during invasion of human erythrocytes. Science. 1985 Jan 11;227(4683):169–171. doi: 10.1126/science.3880920. [DOI] [PubMed] [Google Scholar]
- Orlandi P. A., Sim B. K., Chulay J. D., Haynes J. D. Characterization of the 175-kilodalton erythrocyte binding antigen of Plasmodium falciparum. Mol Biochem Parasitol. 1990 May;40(2):285–294. doi: 10.1016/0166-6851(90)90050-v. [DOI] [PubMed] [Google Scholar]
- Pasvol G., Jungery M. Glycophorins and red cell invasion by Plasmodium falciparum. Ciba Found Symp. 1983;94:174–195. doi: 10.1002/9780470715444.ch11. [DOI] [PubMed] [Google Scholar]
- Pasvol G., Wainscoat J. S., Weatherall D. J. Erythrocytes deficiency in glycophorin resist invasion by the malarial parasite Plasmodium falciparum. Nature. 1982 May 6;297(5861):64–66. doi: 10.1038/297064a0. [DOI] [PubMed] [Google Scholar]
- Pearson W. R., Lipman D. J. Improved tools for biological sequence comparison. Proc Natl Acad Sci U S A. 1988 Apr;85(8):2444–2448. doi: 10.1073/pnas.85.8.2444. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Perkins M. E., Rocco L. J. Sialic acid-dependent binding of Plasmodium falciparum merozoite surface antigen, Pf200, to human erythrocytes. J Immunol. 1988 Nov 1;141(9):3190–3196. [PubMed] [Google Scholar]
- Perkins M. E. Surface proteins of Plasmodium falciparum merozoites binding to the erythrocyte receptor, glycophorin. J Exp Med. 1984 Sep 1;160(3):788–798. doi: 10.1084/jem.160.3.788. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
- Sam-Yellowe T. Y., Perkins M. E. Binding of Plasmodium falciparum rhoptry proteins to mouse erythrocytes and their possible role in invasion. Mol Biochem Parasitol. 1990 Feb;39(1):91–100. doi: 10.1016/0166-6851(90)90011-a. [DOI] [PubMed] [Google Scholar]
- Sim B. K. Sequence conservation of a functional domain of erythrocyte binding antigen 175 in Plasmodium falciparum. Mol Biochem Parasitol. 1990 Jun;41(2):293–295. doi: 10.1016/0166-6851(90)90193-p. [DOI] [PubMed] [Google Scholar]
- Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
- Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Vernes A., Haynes J. D., Tapchaisri P., Williams J. L., Dutoit E., Diggs C. L. Plasmodium falciparum strain-specific human antibody inhibits merozoite invasion of erythrocytes. Am J Trop Med Hyg. 1984 Mar;33(2):197–203. doi: 10.4269/ajtmh.1984.33.197. [DOI] [PubMed] [Google Scholar]
- Weis W., Brown J. H., Cusack S., Paulson J. C., Skehel J. J., Wiley D. C. Structure of the influenza virus haemagglutinin complexed with its receptor, sialic acid. Nature. 1988 Jun 2;333(6172):426–431. doi: 10.1038/333426a0. [DOI] [PubMed] [Google Scholar]
- Wirtz R. A., Burkot T. R., Graves P. M., Andre R. G. Field evaluation of enzyme-linked immunosorbent assays for Plasmodium falciparum and Plasmodium vivax sporozoites in mosquitoes (Diptera: Culicidae) from Papua New Guinea. J Med Entomol. 1987 Jul;24(4):433–437. doi: 10.1093/jmedent/24.4.433. [DOI] [PubMed] [Google Scholar]
- Wirtz R. A., Zavala F., Charoenvit Y., Campbell G. H., Burkot T. R., Schneider I., Esser K. M., Beaudoin R. L., Andre R. G. Comparative testing of monoclonal antibodies against Plasmodium falciparum sporozoites for ELISA development. Bull World Health Organ. 1987;65(1):39–45. [PMC free article] [PubMed] [Google Scholar]
- Young R. A., Davis R. W. Yeast RNA polymerase II genes: isolation with antibody probes. Science. 1983 Nov 18;222(4625):778–782. doi: 10.1126/science.6356359. [DOI] [PubMed] [Google Scholar]