Abstract
We have developed transmission-blocking monoclonal antibodies (MAbs) against Plasmodium yoelii 21-kDa (Pys21) and 28-kDa (Pys25) ookinete surface proteins. These MAbs block infectivity of P. yoelii to Anopheles stephensi. One MAb, 14, cross-reacted by Western blotting with a 28-kDa surface protein (Pbs25) of P. berghei ookinetes and blocked oocyst development, as assayed by direct mosquito feeds on passively immunized P. berghei-infected mice. In total, we have identified two ookinete surface proteins in P. yoelii, one of which is also present in P. berghei. The transmission-blocking activity of the anti-Pys25 MAb 4 was complete and more potent than that of the anti-Pys21 MAb 2. Moreover, Fab fragments of MAb 4 had transmission-blocking activity in mice. In comparison, Fab fragments of MAb 2 did not have detectable transmission-blocking effect, although F(ab')2 did. Furthermore, MAb 2 and MAb 4 appeared to block the in vitro formation and development of zygotes as well.
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- 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]
- Duffy P. E., Pimenta P., Kaslow D. C. Pgs28 belongs to a family of epidermal growth factor-like antigens that are targets of malaria transmission-blocking antibodies. J Exp Med. 1993 Feb 1;177(2):505–510. doi: 10.1084/jem.177.2.505. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fried M., Gwadz R. W., Kaslow D. C. Identification of two cysteine-rich, lipophilic proteins on the surface of Plasmodium knowlesi ookinetes: Pks20 and Pks24. Exp Parasitol. 1994 May;78(3):326–330. doi: 10.1006/expr.1994.1034. [DOI] [PubMed] [Google Scholar]
- 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]
- Kaslow D. C., Bathurst I. C., Lensen T., Ponnudurai T., Barr P. J., Keister D. B. Saccharomyces cerevisiae recombinant Pfs25 adsorbed to alum elicits antibodies that block transmission of Plasmodium falciparum. Infect Immun. 1994 Dec;62(12):5576–5580. doi: 10.1128/iai.62.12.5576-5580.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kaslow D. C., Quakyi I. A., Syin C., Raum M. G., Keister D. B., Coligan J. E., McCutchan T. F., Miller L. H. A vaccine candidate from the sexual stage of human malaria that contains EGF-like domains. Nature. 1988 May 5;333(6168):74–76. doi: 10.1038/333074a0. [DOI] [PubMed] [Google Scholar]
- Kaslow D. C., Syin C., McCutchan T. F., Miller L. H. Comparison of the primary structure of the 25 kDa ookinete surface antigens of Plasmodium falciparum and Plasmodium gallinaceum reveal six conserved regions. Mol Biochem Parasitol. 1989 Mar 15;33(3):283–287. doi: 10.1016/0166-6851(89)90090-x. [DOI] [PubMed] [Google Scholar]
- 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]
- Mage M. G. Preparation of Fab fragments from IgGs of different animal species. Methods Enzymol. 1980;70(A):142–150. doi: 10.1016/s0076-6879(80)70045-9. [DOI] [PubMed] [Google Scholar]
- Nilsson U. R., Müller-Eberhard H. J. Deficiency of the fifth component of complement in mice with an inherited complement defect. J Exp Med. 1967 Jan 1;125(1):1–16. doi: 10.1084/jem.125.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Paton M. G., Barker G. C., Matsuoka H., Ramesar J., Janse C. J., Waters A. P., Sinden R. E. Structure and expression of a post-transcriptionally regulated malaria gene encoding a surface protein from the sexual stages of Plasmodium berghei. Mol Biochem Parasitol. 1993 Jun;59(2):263–275. doi: 10.1016/0166-6851(93)90224-l. [DOI] [PubMed] [Google Scholar]
- Ranawaka G. R., Alejo-Blanco A. R., Sinden R. E. Characterization of the effector mechanisms of a transmission-blocking antibody upon differentiation of Plasmodium berghei gametocytes into ookinetes in vitro. Parasitology. 1994 Jul;109(Pt 1):11–17. doi: 10.1017/s0031182000077702. [DOI] [PubMed] [Google Scholar]
- Ranawaka G. R., Fleck S. L., Blanco A. R., Sinden R. E. Characterization of the modes of action of anti-Pbs21 malaria transmission-blocking immunity: ookinete to oocyst differentiation in vivo. Parasitology. 1994 Nov;109(Pt 4):403–411. doi: 10.1017/s0031182000080653. [DOI] [PubMed] [Google Scholar]
- Read D., Lensen A. H., Begarnie S., Haley S., Raza A., Carter R. Transmission-blocking antibodies against multiple, non-variant target epitopes of the Plasmodium falciparum gamete surface antigen Pfs230 are all complement-fixing. Parasite Immunol. 1994 Oct;16(10):511–519. doi: 10.1111/j.1365-3024.1994.tb00305.x. [DOI] [PubMed] [Google Scholar]
- Sieber K. P., Huber M., Kaslow D., Banks S. M., Torii M., Aikawa M., Miller L. H. The peritrophic membrane as a barrier: its penetration by Plasmodium gallinaceum and the effect of a monoclonal antibody to ookinetes. Exp Parasitol. 1991 Feb;72(2):145–156. doi: 10.1016/0014-4894(91)90132-g. [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]
- Tsuboi T., Cao Y. M., Torii M., Hitsumoto Y., Kanbara H. Murine complement reduces infectivity of Plasmodium yoelii to mosquitoes. Infect Immun. 1995 Sep;63(9):3702–3704. doi: 10.1128/iai.63.9.3702-3704.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Waters A. P., Higgins D. G., McCutchan T. F. Plasmodium falciparum appears to have arisen as a result of lateral transfer between avian and human hosts. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3140–3144. doi: 10.1073/pnas.88.8.3140. [DOI] [PMC free article] [PubMed] [Google Scholar]