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. 1985 Nov 1;162(5):1460–1476. doi: 10.1084/jem.162.5.1460

Sequential expression of antigens on sexual stages of Plasmodium falciparum accessible to transmission-blocking antibodies in the mosquito

PMCID: PMC2187939  PMID: 2865324

Abstract

Plasmodium falciparum gametocytes contain specific antigens, some of which (Mr 230,000, 48,000, 45,000) are expressed on the surface of the newly emerged macrogamete. A different antigen (Mr 25,000) surrounds the surface of the ookinete and, although present to some extent in the developing gametocyte, is synthesized in high quantities by the macrogamete/zygote and expressed progressively on the transforming zygote surface. These antigens are targets of transmission blocking antibodies that are effective at two distinct points after gametogenesis: fertilization of the macrogamete and ookinete to oocyst development. The antigens involved in the fertilization blockade are the Mr 48 and 45 proteins, which are expressed on the macrogamete surface. The Mr 230 K coprecipitating protein probably plays no part in transmission block. mAb directed against the Mr 25 K ookinete surface protein blocked transmission without inhibiting ookinete formation, indicating that this protein has an important role in the transformation of ookinete into oocyst. A combination of mAb recognizing different epitopes on the same protein molecule acted synergistically in inhibiting oocyst formation. Using a mixture of two blocking mAb reacting against the Mr 48/45 and 25 K proteins, respectively, an additive blocking effect could be demonstrated.

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Selected References

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  1. Bray R. S., McCrae A. W., Smalley M. E. Lack of a circadian rhythm in the ability of the gametocytes of Plasmodium falciparum to infect Anopheles gambiae. Int J Parasitol. 1976 Oct;6(5):399–401. doi: 10.1016/0020-7519(76)90025-4. [DOI] [PubMed] [Google Scholar]
  2. Burnette W. N. "Western blotting": electrophoretic transfer of proteins from sodium dodecyl sulfate--polyacrylamide gels to unmodified nitrocellulose and radiographic detection with antibody and radioiodinated protein A. Anal Biochem. 1981 Apr;112(2):195–203. doi: 10.1016/0003-2697(81)90281-5. [DOI] [PubMed] [Google Scholar]
  3. Carter R., Gwadz R. W., Green I. Plasmodium gallinaceum: Transmission-blocking immunity in chickens. II. The effect of antigamete antibodies in vitro and in vivo and their elaboration during infection. Exp Parasitol. 1979 Apr;47(2):194–208. doi: 10.1016/0014-4894(79)90073-0. [DOI] [PubMed] [Google Scholar]
  4. Carter R., Gwadz R. W., McAuliffe F. M. Plasmodium gallinaceum: transmission-blocking immunity in chickens. I. Comparative immunogenicity of gametocyte- and gamete-containing preparations. Exp Parasitol. 1979 Apr;47(2):185–193. doi: 10.1016/0014-4894(79)90072-9. [DOI] [PubMed] [Google Scholar]
  5. Carter R., Kaushal D. C. Characterization of antigens on mosquito midgut stages of Plasmodium gallinaceum. III. Changes in zygote surface proteins during transformation to mature ookinete. Mol Biochem Parasitol. 1984 Oct;13(2):235–241. doi: 10.1016/0166-6851(84)90116-6. [DOI] [PubMed] [Google Scholar]
  6. Chamberlain J. P. Fluorographic detection of radioactivity in polyacrylamide gels with the water-soluble fluor, sodium salicylate. Anal Biochem. 1979 Sep 15;98(1):132–135. doi: 10.1016/0003-2697(79)90716-4. [DOI] [PubMed] [Google Scholar]
  7. De Leij L., Poppema S., The T. H. Cryopreservation of newly formed hybridomas. J Immunol Methods. 1983 Aug 12;62(1):69–72. doi: 10.1016/0022-1759(83)90111-4. [DOI] [PubMed] [Google Scholar]
  8. Gwadz R. W., Green I. Malaria immunization in Rhesus monkeys. A vaccine effective against both the sexual and asexual stages of Plasmodium knowlesi. J Exp Med. 1978 Nov 1;148(5):1311–1323. doi: 10.1084/jem.148.5.1311. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gwadz R. W. Successful immunization against the sexual stages of Plasmodium gallinaceum. Science. 1976 Sep 17;193(4258):1150–1151. doi: 10.1126/science.959832. [DOI] [PubMed] [Google Scholar]
  10. Hancock K., Tsang V. C. India ink staining of proteins on nitrocellulose paper. Anal Biochem. 1983 Aug;133(1):157–162. doi: 10.1016/0003-2697(83)90237-3. [DOI] [PubMed] [Google Scholar]
  11. Hubbard A. L., Cohn Z. A. The enzymatic iodination of the red cell membrane. J Cell Biol. 1972 Nov;55(2):390–405. doi: 10.1083/jcb.55.2.390. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. James G. T. Inactivation of the protease inhibitor phenylmethylsulfonyl fluoride in buffers. Anal Biochem. 1978 Jun 1;86(2):574–579. doi: 10.1016/0003-2697(78)90784-4. [DOI] [PubMed] [Google Scholar]
  13. Kaushal D. C., Carter R. Characterization of antigens on mosquito midgut stages of Plasmodium gallinaceum. II. Comparison of surface antigens of male and female gametes and zygotes. Mol Biochem Parasitol. 1984 Apr;11:145–156. doi: 10.1016/0166-6851(84)90061-6. [DOI] [PubMed] [Google Scholar]
  14. Kaushal D. C., Carter R., Howard R. J., McAuliffe F. M. Characterization of antigens on mosquito midgut stages of Plasmodium gallinaceum. I. Zygote surface antigens. Mol Biochem Parasitol. 1983 May;8(1):53–69. doi: 10.1016/0166-6851(83)90034-8. [DOI] [PubMed] [Google Scholar]
  15. Kaushal D. C., Carter R., Rener J., Grotendorst C. A., Miller L. H., Howard R. J. Monoclonal antibodies against surface determinants on gametes of Plasmodium gallinaceum block transmission of malaria parasites to mosquitoes. J Immunol. 1983 Nov;131(5):2557–2562. [PubMed] [Google Scholar]
  16. Kearney J. F., Radbruch A., Liesegang B., Rajewsky K. A new mouse myeloma cell line that has lost immunoglobulin expression but permits the construction of antibody-secreting hybrid cell lines. J Immunol. 1979 Oct;123(4):1548–1550. [PubMed] [Google Scholar]
  17. Kumar N., Carter R. Biosynthesis of the target antigens of antibodies blocking transmission of Plasmodium falciparum. Mol Biochem Parasitol. 1984 Nov;13(3):333–342. doi: 10.1016/0166-6851(84)90124-5. [DOI] [PubMed] [Google Scholar]
  18. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  19. 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]
  20. Luben R. A., Brazeau P., Böhlen P., Guillemin R. Monoclonal antibodies to hypothalamic growth hormone-releasing factor with picomoles of antigen. Science. 1982 Nov 26;218(4575):887–889. doi: 10.1126/science.6813967. [DOI] [PubMed] [Google Scholar]
  21. McCutchan T. F., Dame J. B., Miller L. H., Barnwell J. Evolutionary relatedness of Plasmodium species as determined by the structure of DNA. Science. 1984 Aug 24;225(4664):808–811. doi: 10.1126/science.6382604. [DOI] [PubMed] [Google Scholar]
  22. Mendis K. N., Targett G. A. Immunisation against gametes and asexual erythrocytic stages of a rodent malaria parasite. Nature. 1979 Feb 1;277(5695):389–391. doi: 10.1038/277389a0. [DOI] [PubMed] [Google Scholar]
  23. Ponnudurai T., Lensen A. H., Leeuwenberg A. D., Meuwissen J. H. Cultivation of fertile Plasmodium falciparum gametocytes in semi-automated systems. 1. Static cultures. Trans R Soc Trop Med Hyg. 1982;76(6):812–818. doi: 10.1016/0035-9203(82)90116-x. [DOI] [PubMed] [Google Scholar]
  24. Ponnudurai T., Lensen A. H., Meuwissen J. H. An automated large-scale culture system of Plasmodium falciparum using tangential flow filtration for medium change. Parasitology. 1983 Dec;87(Pt 3):439–445. doi: 10.1017/s0031182000082962. [DOI] [PubMed] [Google Scholar]
  25. Ponnudurai T., Meuwissen J. H., Leeuwenberg A. D., Verhave J. P., Lensen A. H. The production of mature gametocytes of Plasmodium falciparum in continuous cultures of different isolates infective to mosquitoes. Trans R Soc Trop Med Hyg. 1982;76(2):242–250. doi: 10.1016/0035-9203(82)90289-9. [DOI] [PubMed] [Google Scholar]
  26. Rener J., Carter R., Rosenberg Y., Miller L. H. Anti-gamete monoclonal antibodies synergistically block transmission of malaria by preventing fertilization in the mosquito. Proc Natl Acad Sci U S A. 1980 Nov;77(11):6797–6799. doi: 10.1073/pnas.77.11.6797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Rener J., Graves P. M., Carter R., Williams J. L., Burkot T. R. Target antigens of transmission-blocking immunity on gametes of plasmodium falciparum. J Exp Med. 1983 Sep 1;158(3):976–981. doi: 10.1084/jem.158.3.976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Sinden R. E., Canning E. U., Bray R. S., Smalley M. E. Gametocyte and gamete development in Plasmodium falciparum. Proc R Soc Lond B Biol Sci. 1978 Jun 5;201(1145):375–399. doi: 10.1098/rspb.1978.0051. [DOI] [PubMed] [Google Scholar]
  29. Tamura G. S., Dailey M. O., Gallatin W. M., McGrath M. S., Weissman I. L., Pillemer E. A. Isolation of molecules recognized by monoclonal antibodies and antisera: the solid phase immunoisolation technique. Anal Biochem. 1984 Feb;136(2):458–464. doi: 10.1016/0003-2697(84)90244-6. [DOI] [PubMed] [Google Scholar]
  30. 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]
  31. 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]
  32. Vermeulen A. N., Ponnudurai T., Lensen A. H., Roeffen W. F., Meuwissen J. E. The purification of Plasmodium falciparum macrogametes and/or zygotes prepared from in vitro cultures. Trans R Soc Trop Med Hyg. 1983;77(6):753–755. doi: 10.1016/0035-9203(83)90280-8. [DOI] [PubMed] [Google Scholar]
  33. Vermeulen A. N., Roeffen W. F., Van Munster J. C., Meuwissen J. H. Isolation and characterization of membrane proteins of Plasmodium berghei sporozoites. Mol Biochem Parasitol. 1983 Mar;7(3):197–207. doi: 10.1016/0166-6851(83)90021-x. [DOI] [PubMed] [Google Scholar]
  34. Zavala F., Cochrane A. H., Nardin E. H., Nussenzweig R. S., Nussenzweig V. Circumsporozoite proteins of malaria parasites contain a single immunodominant region with two or more identical epitopes. J Exp Med. 1983 Jun 1;157(6):1947–1957. doi: 10.1084/jem.157.6.1947. [DOI] [PMC free article] [PubMed] [Google Scholar]

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