Abstract
Pfs25 is a sexual stage antigen of Plasmodium falciparum that is expressed on the surface of zygote and ookinete forms of the parasite. Monoclonal antibodies directed against native Pfs25 can block completely the development of P. falciparum oocysts in the midgut of the mosquito vector. Thus, this 25-kD protein is a potential vaccine candidate for eliciting transmission-blocking immunity in inhabitants of malaria endemic regions. We have synthesized, by secretion from yeast, a polypeptide analogue of Pfs25 that reacts with conformation- dependent monoclonal antibodies, and elicits transmission-blocking antibodies when used to immunize mice and monkeys in conjunction with a muramyl tripeptide adjuvant. Our results suggest the further evaluation of recombinant DNA-derived Pfs25 in transmission-blocking vaccination studies in humans.
Full Text
The Full Text of this article is available as a PDF (627.5 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Abrignani S., Montagna D., Jeannet M., Wintsch J., Haigwood N. L., Shuster J. R., Steimer K. S., Cruchaud A., Staehelin T. Priming of CD4+ T cells specific for conserved regions of human immunodeficiency virus glycoprotein gp120 in humans immunized with a recombinant envelope protein. Proc Natl Acad Sci U S A. 1990 Aug;87(16):6136–6140. doi: 10.1073/pnas.87.16.6136. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Barr P. J., Cousens L. S., Lee-Ng C. T., Medina-Selby A., Masiarz F. R., Hallewell R. A., Chamberlain S. H., Bradley J. D., Lee D., Steimer K. S. Expression and processing of biologically active fibroblast growth factors in the yeast Saccharomyces cerevisiae. J Biol Chem. 1988 Nov 5;263(31):16471–16478. [PubMed] [Google Scholar]
- Barr P. J., Inselburg J., Green K. M., Kansopon J., Hahm B. K., Gibson H. L., Lee-Ng C. T., Bzik D. J., Li W. B., Bathurst I. C. Immunogenicity of recombinant Plasmodium falciparum SERA proteins in rodents. Mol Biochem Parasitol. 1991 Mar;45(1):159–170. doi: 10.1016/0166-6851(91)90038-8. [DOI] [PubMed] [Google Scholar]
- Brake A. J., Merryweather J. P., Coit D. G., Heberlein U. A., Masiarz F. R., Mullenbach G. T., Urdea M. S., Valenzuela P., Barr P. J. Alpha-factor-directed synthesis and secretion of mature foreign proteins in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1984 Aug;81(15):4642–4646. doi: 10.1073/pnas.81.15.4642. [DOI] [PMC free article] [PubMed] [Google Scholar]
- George-Nascimento C., Gyenes A., Halloran S. M., Merryweather J., Valenzuela P., Steimer K. S., Masiarz F. R., Randolph A. Characterization of recombinant human epidermal growth factor produced in yeast. Biochemistry. 1988 Jan 26;27(2):797–802. doi: 10.1021/bi00402a046. [DOI] [PubMed] [Google Scholar]
- Gill G. N., Kawamoto T., Cochet C., Le A., Sato J. D., Masui H., McLeod C., Mendelsohn J. Monoclonal anti-epidermal growth factor receptor antibodies which are inhibitors of epidermal growth factor binding and antagonists of epidermal growth factor binding and antagonists of epidermal growth factor-stimulated tyrosine protein kinase activity. J Biol Chem. 1984 Jun 25;259(12):7755–7760. [PubMed] [Google Scholar]
- Gordon D. M., Cosgriff T. M., Schneider I., Wasserman G. F., Majarian W. R., Hollingdale M. R., Chulay J. D. Safety and immunogenicity of a Plasmodium vivax sporozoite vaccine. Am J Trop Med Hyg. 1990 Jun;42(6):527–531. doi: 10.4269/ajtmh.1990.42.527. [DOI] [PubMed] [Google Scholar]
- 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]
- Quakyi I. A., Carter R., Rener J., Kumar N., Good M. F., Miller L. H. The 230-kDa gamete surface protein of Plasmodium falciparum is also a target for transmission-blocking antibodies. J Immunol. 1987 Dec 15;139(12):4213–4217. [PubMed] [Google Scholar]
- Shuster J. R. Regulated transcriptional systems for the production of proteins in yeast: regulation by carbon source. Biotechnology. 1989;13:83–108. [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]