Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1993 Feb 1;177(2):273–281. doi: 10.1084/jem.177.2.273

Pfs2400 can mediate antibody-dependent malaria transmission inhibition and may be the Plasmodium falciparum 11.1 gene product

PMCID: PMC2190917  PMID: 8426106

Abstract

Monoclonal antibodies (mAb) have been raised against Plasmodium falciparum gametocyte stage protein extracts, in an effort to identify novel parasite antigens that might mediate malaria transmission- blocking immunity. mAb 1A1 identified Pfs2400, a sexual stage-specific antigen of greater than 2 megadaltons, that is associated with the outer leaflet of the parasitophorous vacuole membrane in mature circulating gametocyte-infected red blood cells. Upon induction of gametogenesis, Pfs2400 partitions between the gamete plasmalemma and the degenerating erythrocyte membrane. The antigen is no longer detectable in the fully emerged gamete. mAb 1A1 dramatically reduces the number of oocysts formed in P. falciparum gametocyte-fed mosquitoes. The cognate antigen is probably the product of the Pf11.1 gene (Scherf et al. 1988. EMBO [Eur. Mol. Biol. Organ.]J. 7:1129) on the basis that a peptide composed of two copies of the degenerate nine amino acid repeat sequence in the Pf11.1 protein, can inhibit binding of mAb1A1 to the native antigen. The mechanism of transmission inhibition mediated by the Pfs2400 is discussed.

Full Text

The Full Text of this article is available as a PDF (1.9 MB).

Selected References

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

  1. Barr P. J., Green K. M., Gibson H. L., Bathurst I. C., Quakyi I. A., Kaslow D. C. Recombinant Pfs25 protein of Plasmodium falciparum elicits malaria transmission-blocking immunity in experimental animals. J Exp Med. 1991 Nov 1;174(5):1203–1208. doi: 10.1084/jem.174.5.1203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Carter R., Graves P. M., Creasey A., Byrne K., Read D., Alano P., Fenton B. Plasmodium falciparum: an abundant stage-specific protein expressed during early gametocyte development. Exp Parasitol. 1989 Aug;69(2):140–149. doi: 10.1016/0014-4894(89)90182-3. [DOI] [PubMed] [Google Scholar]
  3. Carter R., Graves P. M., Quakyi I. A., Good M. F. Restricted or absent immune responses in human populations to Plasmodium falciparum gamete antigens that are targets of malaria transmission-blocking antibodies. J Exp Med. 1989 Jan 1;169(1):135–147. doi: 10.1084/jem.169.1.135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Carter R., Kumar N., Quakyi I., Good M., Mendis K., Graves P., Miller L. Immunity to sexual stages of malaria parasites. Prog Allergy. 1988;41:193–214. [PubMed] [Google Scholar]
  5. Carter R., Miller L. H. Evidence for environmental modulation of gametocytogenesis in Plasmodium falciparum in continuous culture. Bull World Health Organ. 1979;57 (Suppl 1):37–52. [PMC free article] [PubMed] [Google Scholar]
  6. Carter R., Miller L. H., Rener J., Kaushal D. C., Kumar N., Graves P. M., Grotendorst C. A., Gwadz R. W., French C., Wirth D. Target antigens in malaria transmission blocking immunity. Philos Trans R Soc Lond B Biol Sci. 1984 Nov 13;307(1131):201–213. doi: 10.1098/rstb.1984.0120. [DOI] [PubMed] [Google Scholar]
  7. David P. H., del Portillo H. A., Mendis K. N. Plasmodium vivax malaria: parasite biology defines potential targets for vaccine development. Biol Cell. 1988;64(2):251–260. doi: 10.1016/0248-4900(88)90084-6. [DOI] [PubMed] [Google Scholar]
  8. Graves P. M., Carter R., Burkot T. R., Quakyi I. A., Kumar N. Antibodies to Plasmodium falciparum gamete surface antigens in Papua New Guinea sera. Parasite Immunol. 1988 Mar;10(2):209–218. doi: 10.1111/j.1365-3024.1988.tb00215.x. [DOI] [PubMed] [Google Scholar]
  9. Grotendorst C. A., Kumar N., Carter R., Kaushal D. C. A surface protein expressed during the transformation of zygotes of Plasmodium gallinaceum is a target of transmission-blocking antibodies. Infect Immun. 1984 Sep;45(3):775–777. doi: 10.1128/iai.45.3.775-777.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. Harte P. G., Rogers N., Targett G. A. Vaccination with purified microgamete antigens prevents transmission of rodent malaria. Nature. 1985 Jul 18;316(6025):258–259. doi: 10.1038/316258a0. [DOI] [PubMed] [Google Scholar]
  12. Kaslow D. C., Isaacs S. N., Quakyi I. A., Gwadz R. W., Moss B., Keister D. B. Induction of Plasmodium falciparum transmission-blocking antibodies by recombinant vaccinia virus. Science. 1991 May 31;252(5010):1310–1313. doi: 10.1126/science.1925544. [DOI] [PubMed] [Google Scholar]
  13. Kaslow D. C., Quakyi I. A., Keister D. B. Minimal variation in a vaccine candidate from the sexual stage of Plasmodium falciparum. Mol Biochem Parasitol. 1989 Jan 1;32(1):101–103. doi: 10.1016/0166-6851(89)90134-5. [DOI] [PubMed] [Google Scholar]
  14. Knobloch J., Schreiber M., Grokhovsky S., Scherf A. Specific and nonspecific immunodiagnostic properties of recombinant and synthetic Plasmodium falciparum antigens. Eur J Clin Microbiol. 1987 Oct;6(5):547–551. doi: 10.1007/BF02014244. [DOI] [PubMed] [Google Scholar]
  15. Koenen M., Scherf A., Mercereau O., Langsley G., Sibilli L., Dubois P., Pereira da Silva L., Müller-Hill B. Human antisera detect a Plasmodium falciparum genomic clone encoding a nonapeptide repeat. 1984 Sep 27-Oct 3Nature. 311(5984):382–385. doi: 10.1038/311382a0. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Kurzban G. P., Wang K. Giant polypeptides of skeletal muscle titin: sedimentation equilibrium in guanidine hydrochloride. Biochem Biophys Res Commun. 1988 Feb 15;150(3):1155–1161. doi: 10.1016/0006-291x(88)90750-4. [DOI] [PubMed] [Google Scholar]
  18. Lambros C., Vanderberg J. P. Synchronization of Plasmodium falciparum erythrocytic stages in culture. J Parasitol. 1979 Jun;65(3):418–420. [PubMed] [Google Scholar]
  19. Lensen A. H., Van Gemert G. J., Bolmer M. G., Meis J. F., Kaslow D., Meuwissen J. H., Ponnudurai T. Transmission blocking antibody of the Plasmodium falciparum zygote/ookinete surface protein Pfs25 also influences sporozoite development. Parasite Immunol. 1992 Sep;14(5):471–479. doi: 10.1111/j.1365-3024.1992.tb00021.x. [DOI] [PubMed] [Google Scholar]
  20. Mendis C., Gamage-Mendis A. C., De Zoysa A. P., Abhayawardena T. A., Carter R., Herath P. R., Mendis K. N. Characteristics of malaria transmission in Kataragama, Sri Lanka: a focus for immuno-epidemiological studies. Am J Trop Med Hyg. 1990 Apr;42(4):298–308. doi: 10.4269/ajtmh.1990.42.298. [DOI] [PubMed] [Google Scholar]
  21. Mendis K. N., Munesinghe Y. D., de Silva Y. N., Keragalla I., Carter R. Malaria transmission-blocking immunity induced by natural infections of Plasmodium vivax in humans. Infect Immun. 1987 Feb;55(2):369–372. doi: 10.1128/iai.55.2.369-372.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Meuwissen J. H. Current studies related to the development of transmission-blocking malaria vaccines: a review. Trans R Soc Trop Med Hyg. 1989;83 (Suppl):57–60. doi: 10.1016/0035-9203(89)90605-6. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Petersen C., Nelson R., Leech J., Jensen J., Wollish W., Scherf A. The gene product of the Plasmodium falciparum 11.1 locus is a protein larger than one megadalton. Mol Biochem Parasitol. 1990 Sep-Oct;42(2):189–195. doi: 10.1016/0166-6851(90)90161-e. [DOI] [PubMed] [Google Scholar]
  25. Pologe L. G., Pavlovec A., Shio H., Ravetch J. V. Primary structure and subcellular localization of the knob-associated histidine-rich protein of Plasmodium falciparum. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7139–7143. doi: 10.1073/pnas.84.20.7139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. 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]
  27. 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]
  28. Potocnjak P., Yoshida N., Nussenzweig R. S., Nussenzweig V. Monovalent fragments (Fab) of monoclonal antibodies to a sporozoite surface antigen (Pb44) protect mice against malarial infection. J Exp Med. 1980 Jun 1;151(6):1504–1513. doi: 10.1084/jem.151.6.1504. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Pringle G. A quantitative study of naturally-acquired malaria infections in Anopheles gambiae and Anopheles funestus in a highly malarious area of East Africa. Trans R Soc Trop Med Hyg. 1966;60(5):626–632. doi: 10.1016/0035-9203(66)90009-5. [DOI] [PubMed] [Google Scholar]
  30. Quakyi I. A., Matsumoto Y., Carter R., Udomsangpetch R., Sjolander A., Berzins K., Perlmann P., Aikawa M., Miller L. H. Movement of a falciparum malaria protein through the erythrocyte cytoplasm to the erythrocyte membrane is associated with lysis of the erythrocyte and release of gametes. Infect Immun. 1989 Mar;57(3):833–839. doi: 10.1128/iai.57.3.833-839.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Quakyi I. A., Otoo L. N., Pombo D., Sugars L. Y., Menon A., De Groot A. S., Johnson A., Alling D., Miller L. H., Good M. F. Differential non-responsiveness in humans of candidate Plasmodium falciparum vaccine antigens. Am J Trop Med Hyg. 1989 Aug;41(2):125–134. [PubMed] [Google Scholar]
  32. 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]
  33. Scherf A., Carter R., Petersen C., Alano P., Nelson R., Aikawa M., Mattei D., Pereira da Silva L., Leech J. Gene inactivation of Pf11-1 of Plasmodium falciparum by chromosome breakage and healing: identification of a gametocyte-specific protein with a potential role in gametogenesis. EMBO J. 1992 Jun;11(6):2293–2301. doi: 10.1002/j.1460-2075.1992.tb05288.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Scherf A., Hilbich C., Sieg K., Mattei D., Mercereau-Puijalon O., Müller-Hill B. The 11-1 gene of Plasmodium falciparum codes for distinct fast evolving repeats. EMBO J. 1988 Apr;7(4):1129–1137. doi: 10.1002/j.1460-2075.1988.tb02922.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Udomsangpetch R., Carlsson J., Wåhlin B., Holmquist G., Ozaki L. S., Scherf A., Mattei D., Mercereau-Puijalon O., Uni S., Aikawa M. Reactivity of the human monoclonal antibody 33G2 with repeated sequences of three distinct Plasmodium falciparum antigens. J Immunol. 1989 May 15;142(10):3620–3626. [PubMed] [Google Scholar]
  36. Vermeulen A. N., Ponnudurai T., Beckers P. J., Verhave J. P., Smits M. A., Meuwissen J. H. Sequential expression of antigens on sexual stages of Plasmodium falciparum accessible to transmission-blocking antibodies in the mosquito. J Exp Med. 1985 Nov 1;162(5):1460–1476. doi: 10.1084/jem.162.5.1460. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Walliker D., Quakyi I. A., Wellems T. E., McCutchan T. F., Szarfman A., London W. T., Corcoran L. M., Burkot T. R., Carter R. Genetic analysis of the human malaria parasite Plasmodium falciparum. Science. 1987 Jun 26;236(4809):1661–1666. doi: 10.1126/science.3299700. [DOI] [PubMed] [Google Scholar]
  38. Wizel B., Kumar N. Identification of a continuous and cross-reacting epitope for Plasmodium falciparum transmission-blocking immunity. Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9533–9537. doi: 10.1073/pnas.88.21.9533. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES