Abstract
Serum samples from Aotus trivirgatus subsp. griseimembra monkeys obtained at different stages of a vaccination experiment were analyzed for total antibody titer to Plasmodium falciparum and were used for identifying protective antigens of the human malaria parasite. Total malarial antibody titers were higher in serum samples from protected monkeys (vaccinated with antigen in an adjuvant) than in those from unprotected monkeys (vaccinated with either antigen or adjuvant only). Parasite proteins were labeled with [3H]isoleucine, solubilized with nonionic detergent, and reacted with immune Aotus sera. Immunoprecipitates obtained were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fluorography. Thirteen protein antigen bands in the molecular weight range 73,000 to 180,000 were resolved. Serum samples obtained from protected Aotus monkeys reacted more intensely with these proteins than samples from unprotected monkeys did. Evidence is presented that the protective antigen is not a single, normally nonimmunogenic, protein that is recognized only in protected monkeys. Rather, the present data indicate that a heightened immune response to multiple proteins correlated with in vivo protection to P. falciparum in Aotus monkeys. This finding may have a significant bearing on strategies for the development of a human P. falciparum vaccine.
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- Bonner W. M., Laskey R. A. A film detection method for tritium-labelled proteins and nucleic acids in polyacrylamide gels. Eur J Biochem. 1974 Jul 1;46(1):83–88. doi: 10.1111/j.1432-1033.1974.tb03599.x. [DOI] [PubMed] [Google Scholar]
- Brown G. V., Anders R. F., Mitchell G. F., Heywood P. F. Target antigens of purified human immunoglobulins which inhibit growth of Plasmodium falciparum in vitro. Nature. 1982 Jun 17;297(5867):591–593. doi: 10.1038/297591a0. [DOI] [PubMed] [Google Scholar]
- Brown G. V., Anders R. F., Stace J. D., Alpers M. P., Mitchell G. F. Immunoprecipitation of biosynthetically-labelled proteins from different Papua New Guinea Plasmodium falciparum isolates by sera from individuals in the endemic area. Parasite Immunol. 1981 Winter;3(4):283–298. doi: 10.1111/j.1365-3024.1981.tb00407.x. [DOI] [PubMed] [Google Scholar]
- Butcher G. A., Mitchell G. H., Cohen S. Antibody mediated mechanisms of immunity to malaria induced by vaccination with Plasmodium knowlesi merozoites. Immunology. 1978 Jan;34(1):77–86. [PMC free article] [PubMed] [Google Scholar]
- COHEN S., McGREGOR I. A., CARRINGTON S. Gamma-globulin and acquired immunity to human malaria. Nature. 1961 Nov 25;192:733–737. doi: 10.1038/192733a0. [DOI] [PubMed] [Google Scholar]
- Cochrane A. H., Santoro F., Nussenzweig V., Gwadz R. W., Nussenzweig R. S. Monoclonal antibodies identify the protective antigens of sporozoites of Plasmodium knowlesi. Proc Natl Acad Sci U S A. 1982 Sep;79(18):5651–5655. doi: 10.1073/pnas.79.18.5651. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ellis J., Ozaki L. S., Gwadz R. W., Cochrane A. H., Nussenzweig V., Nussenzweig R. S., Godson G. N. Cloning and expression in E. coli of the malarial sporozoite surface antigen gene from Plasmodium knowlesi. Nature. 1983 Apr 7;302(5908):536–538. doi: 10.1038/302536a0. [DOI] [PubMed] [Google Scholar]
- Holder A. A., Freeman R. R. Biosynthesis and processing of a Plasmodium falciparum schizont antigen recognized by immune serum and a monoclonal antibody. J Exp Med. 1982 Nov 1;156(5):1528–1538. doi: 10.1084/jem.156.5.1528. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Holder A. A., Freeman R. R. Immunization against blood-stage rodent malaria using purified parasite antigens. Nature. 1981 Nov 26;294(5839):361–364. doi: 10.1038/294361a0. [DOI] [PubMed] [Google Scholar]
- Kessler S. W. Rapid isolation of antigens from cells with a staphylococcal protein A-antibody adsorbent: parameters of the interaction of antibody-antigen complexes with protein A. J Immunol. 1975 Dec;115(6):1617–1624. [PubMed] [Google Scholar]
- Kilejian A. Stage-specific proteins and glycoproteins of plasmodium falciparum: identification of antigens unique to schizonts and merozoites. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3695–3699. doi: 10.1073/pnas.77.6.3695. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kramer K. J., Kan S. C., Siddiqui W. A. Concentration of Plasmodium falciparum-infected erythrocytes by density gradient centrifugation in Percoll. J Parasitol. 1982 Apr;68(2):336–337. [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]
- Mitchell G. H., Richards W. H., Butcher G. A., Cohen S. Merozoite vaccination of douroucouli monkeys against falciparum malaria. Lancet. 1977 Jun 25;1(8026):1335–1338. doi: 10.1016/s0140-6736(77)92551-x. [DOI] [PubMed] [Google Scholar]
- Palmer K. L., Hui G. S., Siddiqui W. A., Palmer E. L. A large-scale in vitro production system for Plasmodium falciparum. J Parasitol. 1982 Dec;68(6):1180–1183. [PubMed] [Google Scholar]
- Perrin L. H., Dayal R., Rieder H. Characterization of antigens from erythrocytic stages of Plasmodium falciparum reacting with human immune sera. Trans R Soc Trop Med Hyg. 1981;75(1):163–165. doi: 10.1016/0035-9203(81)90055-9. [DOI] [PubMed] [Google Scholar]
- Reese R. T., Motyl M. R., Hofer-Warbinek R. Reaction of immune sera with components of the human malarial parasite, Plasmodium falciparum. Am J Trop Med Hyg. 1981 Nov;30(6):1168–1178. doi: 10.4269/ajtmh.1981.30.1168. [DOI] [PubMed] [Google Scholar]
- Reese R. T., Trager W., Jensen J. B., Miller D. A., Tantravahi R. Immunization against malaria with antigen from Plasmodium falciparum cultivated in vitro. Proc Natl Acad Sci U S A. 1978 Nov;75(11):5665–5668. doi: 10.1073/pnas.75.11.5665. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Siddiqui W. A. An effective immunization of experimental monkeys against a human malaria parasite, Plasmodium falciparum. Science. 1977 Jul 22;197(4301):388–389. doi: 10.1126/science.406671. [DOI] [PubMed] [Google Scholar]
- Siddiqui W. A., Kan S. C., Kramer K., Case S., Palmer K., Niblack J. F. Use of a synthetic adjuvant in an effective vaccination of monkeys against malaria. Nature. 1981 Jan 1;289(5793):64–66. doi: 10.1038/289064a0. [DOI] [PubMed] [Google Scholar]
- Siddiqui W. A., Taylor D. W., Kan S. C., Kramer K., Richmond-Crum S. M., Kotani S., Shiba T., Kusumoto S. Vaccination of experimental monkeys against Plasmodium falciparum: a possible safe adjuvant. Science. 1978 Sep 29;201(4362):1237–1239. doi: 10.1126/science.99814. [DOI] [PubMed] [Google Scholar]
- VOLLER A., BRAY R. S. Fluorescent antibody staining as a measure of malarial antibody. Proc Soc Exp Biol Med. 1962 Aug-Sep;110:907–910. doi: 10.3181/00379727-110-27687. [DOI] [PubMed] [Google Scholar]
- Weber K., Osborn M. The reliability of molecular weight determinations by dodecyl sulfate-polyacrylamide gel electrophoresis. J Biol Chem. 1969 Aug 25;244(16):4406–4412. [PubMed] [Google Scholar]
- Yoshida N., Nussenzweig R. S., Potocnjak P., Nussenzweig V., Aikawa M. Hybridoma produces protective antibodies directed against the sporozoite stage of malaria parasite. Science. 1980 Jan 4;207(4426):71–73. doi: 10.1126/science.6985745. [DOI] [PubMed] [Google Scholar]