Skip to main content Accessibility help

Characterization of the effector mechanisms of a transmission-blocking antibody upon differentiation of Plasmodium berghei gametocytes into ookinetes in vitro

  • G. R. R. Ranawaka (a1), A. R. Alejo-Blanco (a1) and R. E. Sinden (a1)


The transmission-blocking monoclonal antibody 13.1, which recognizes the ookinete surface antigen Pbs21 of Plasmodium berghei, and an IgG2a isotype control antibody 26.37 were purified by caprylic acid and ammonium sulphate precipitation. Fab fragments were prepared by papain digestion. IgG but not Fab from antibody 13.1 reduced ookinete formation by P. berghei in culture by as much as 94% at a concentration of 100 μg/ml. There was little difference in antibody efficacy in the range 6·25–400 μg/ml in this assay. The parasite was most sensitive to antibody activity in the first 6–9 h of culture, i.e. the gamete/zygote and early retort stages. Peripheral blood leucocytes (PBL) were essential to achieve maximal inhibition by mAb 13.1 (activity was abrogated totally if PBL were removed). Together the data suggest that one of the mechanisms of action of this antibody is antibody-mediated PBL killing. Phagocytosis of parasites was noted in these experiments in all cultures. We have not attempted in this study to distinguish between Fc-mediated opsonization, as opposed to antibody-dependent cellular cytotoxicity.



Hide All
Aikawa, M., Rener, J., Carter, R. & Miller, L. H. (1981). An electron microscopical study of the interaction of monoclonal antibodies with gametes of the malarial parasite Plasmodium gallinaceum. Journal of Protozoology 28, 383–8.
Barr, P. J., Green, K. M., Gibson, H. L., Bathurst, I. C., Quakyi, I. A. & Kaslow, D. C. (1991). Recombinant Pfs25 protein of Plasmodium falciparum elicits malaria transmission-blocking immunity in experimental animals. Journal of Experimental Medicine 174, 1203–8.
Billingsley, P. F., Medley, G. F., Charlwood, J. D. & Sinden, R. E. (1994). Relationship between prevalence and intensity of Plasmodium falciparum infection in natural populations of Anopheles mosquitoes. American Journal of Tropical Medicine and Hygiene (in the Press).
Blobel, C. P., Wolfsberg, T. G., Turck, C. W., Myles, D. G., Primakoff, P. & White, J. M. (1992). A potential fusion peptide and an integrin ligand domain in a protein active in sperm-egg fusion. Nature, London 356, 248–52.
Carter, R., Graves, P. M., Keister, D. B. & Quakyi, I. A. (1990). Properties of epitopes of Pfs48/45, a target of transmission-blocking monoclonal antibodies, on gametes of different isolates of Plasmodium falciparum. Parasite Immunology 12, 587603.
Duffy, P. E., Pimenta, P. & Kaslow, D. C. (1993). Pgs28 belongs to a family of epidermal growth factor like antigens that are targets of malaria transmission-blocking antibodies. Journal of Experimental Medicine 177, 505–10.
Grotendorst, C. A. & Carter, R. (1987). Complement effects on the infectivity of Plasmodium gallinaceum to Aedes aegypti mosquitoes. II. Changes in sensitivity to complement-like factors during zygote development. Journal of Parasitology 73, 980–4.
Grotendorst, C. A., Carter, R., Rosenberg, R. & Koontz, L. (1986). Complement effects on the infectivity of Plasmodium gallinaceum to Aedes aegypti mosquitoes. I. Resistance of zygotes to the alternative pathway of complement. Journal of Immunology 136, 4270–4.
Janse, C. J., Rouwenhorst, R. J., Klooster Van Der, P. F. J., Kaay Van Der, H. J. & Overdulve, J. P. (1985). Development of Plasmodium berghei ookinetes in the midgut of Anopheles atroparvus mosquitoes and in vitro. Parasitology 91, 219–25.
Kaslow, D. C., Bathurst, I. C. & Barr, P. J. (1992). Malaria transmission-blocking vaccines. Trends in Biotechnology 10, 388–91.
Kaushal, D. C., Carter, R., Rener, J., Grotendorst, C. A., Miller, L. H. & Howard, R. J. (1983). Monoclonal antibodies against surface determinants on gametes of Plasmodium gallinaceum block transmission of malaria parasites to mosquitoes. Journal of Immunology 131, 2557–62.
Kumar, N. & Carter, R. (1985). Biosynthesis of two stage-specific membrane proteins during transformation of Plasmodium gallinaceum zygotes into ookinetes. Molecular and Biochemical Parasitology 14, 127–39.
Parham, P. (1986). Preparation and purification of active fragments from mouse monoclonal antibodies. In Handbook of Experimental Immunology, (ed. Weir, D. M.) pp. 14.114.23. London: Blackwell Scientific Publications.
Ponnudurai, T., Van Gemert, G. J., Bensink, T., Lensen, A. H. W. & Meuwissen, J. H. E. TH. (1987). Transmission blockade of Plasmodium falciparum: its variability with gametocyte numbers and concentration of antibody. Transactions of the Royal Society of Tropical Medicine and Hygiene 81, 491–3.
Quakyi, I. A., Carter, R., Rener, J., Kumar, N., Good, M. F. & Miller, L. H. (1987). The 230-kDa gamete surface protein of Plasmodium falciparum is also a target for transmission-blocking antibodies. Journal of Immunology 139, 4213–17.
Ranawaka, G., Alejo-Blanco, R. & Sinden, R. E. (1993). The effect of transmission-blocking antibody ingested in primary and secondary blood feeds, upon the development of Plasmodium berghei in the mosquito vector. Parasitology 107, 225–31.
Rener, J., Graves, P. M., Carter, R., Williams, J. L. & Burkot, T. (1983). Target antigens of transmission-blocking immunity on gametes of Plasmodium falciparum. Journal of Experimental Medicine 158, 971–6.
Rutledge, L. C., Gould, D. J. & Tantichareon, B. (1969). Factors affecting the infection of anophelines with human malaria in Thailand. Transactions of the Royal Society of Tropical Medicine and Hygiene 63, 613–19.
Sieber, K.-P., Huber, M., Kaslow, D., Banks, S. M., Torii, M., Aikawa, M. & Miller, L. H. (1991). The peritrophic membrane as a barrier: its penetration by Plasmodium gallinaceum and the effect of a monoclonal antibody to ookinetes. Experimental Parasitology 72, 145–56.
Simonetti, A. B., Billingsley, P. F., Winger, L. A. & Sinden, R. E. (1993). Kinetics of expression of two major Plasmodium berghei antigens in the mosquito vector Anopheles stephensi. Journal of Eukaryotic Microbiology 40, (in the Press).
Sinden, R. E., Canning, E. U. & Spain, B. (1976). Gametogenesis and fertilization in Plasmodium yoelii nigeriensis: a transmission electron microscope study. Proceedings of The Royal Society, London B 193, 5576.
Sinden, R. E., Hartley, R. H. & Winger, L. (1985). The development of Plasmodium ookinetes in vitro: an ultrastructural study including a description of meiotic division. Parasitology 91, 227–44.
Sinden, R. E. & Smalley, M. J. (1976). Gametocytes of Plasmodium falciparum: phagocytosis by leucocytes in vivo and in vitro. Transactions of the Royal Society of Tropical Hygiene and Medicine 70, 344–5.
Sinden, R. E., Winger, L. A., Hartley, R. H., Carter, H. E., Tirawanchai, N., Davies, C. S. & Sluiters, J. G. (1987). Ookinete antigens of Plasmodium berghei: a light and electron microscopic immunogold study of the 21kD determinant recognized by transmission blocking antibodies. Proceedings of The Royal Society, London, B 230, 443–58.
Tirawanchai, N., Winger, L. A., Nicholas, J. & Sinden, R. E. (1991). Analysis of immunity induced by the affinity-purified 21 -kilodalton zygote–ookinete surface antigen of Plasmodium berghei. Infection and Immunity 59, 3644.
Vermeulen, A. N., Deursen, J. V., Brakenhof, R. H., Lensen, T. H. W., Ponnudurai, T. & Meuwissen, J. H. E. T. (1986). Characterization of Plasmodium falciparum sexual stage antigens and their biosynthesis in synchronized gametocyte cultures. Molecular and Biochemical Parasitology 20, 155–63.
Winger, L. A., Smith, J. E., Nicholas, J., Carter, H. E., Tirawanchai, N. & Sinden, R. E. (1988). Ookinete antigens of Plasmodium berghei. Appearance on the zygote of an Mr 21 K surface determinant identified by transmission-blocklng monoclonal antibodies. Parasite Immunology 10, 193207.


Characterization of the effector mechanisms of a transmission-blocking antibody upon differentiation of Plasmodium berghei gametocytes into ookinetes in vitro

  • G. R. R. Ranawaka (a1), A. R. Alejo-Blanco (a1) and R. E. Sinden (a1)


Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed