Abstract
Merozoite surface protein 1, one of the major surface proteins of the invasive blood stage of the malaria parasite, is a prime candidate for the development of a vaccine against the human disease. Previously, monoclonal antibodies which both inhibited the growth of Plasmodium falciparum in vitro and bound to the first of two epidermal growth factor-like modules located near the carboxy terminus of the protein had been identified. In this study, we have used affinity chromatography on a recombinant fusion protein corresponding to the first epidermal growth factor-like module in P. falciparum merozoite surface protein 1 to prepare antibody induced by natural infection. The antibody was purified from the total immunoglobulin G fraction of adult West African donors, shown to passively confer immunity against falciparum malaria. Such affinity-purified antibodies were shown to recognize the native protein by a number of separate criteria and to block the binding of an inhibitory monoclonal antibody, but they failed to inhibit parasite invasion in an in vitro growth assay. These results indicate that antibody alone is not sufficient to interfere with erythrocyte invasion.
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- Blackman M. J., Chappel J. A., Shai S., Holder A. A. A conserved parasite serine protease processes the Plasmodium falciparum merozoite surface protein-1. Mol Biochem Parasitol. 1993 Nov;62(1):103–114. doi: 10.1016/0166-6851(93)90182-w. [DOI] [PubMed] [Google Scholar]
- Blackman M. J., Heidrich H. G., Donachie S., McBride J. S., Holder A. A. A single fragment of a malaria merozoite surface protein remains on the parasite during red cell invasion and is the target of invasion-inhibiting antibodies. J Exp Med. 1990 Jul 1;172(1):379–382. doi: 10.1084/jem.172.1.379. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Blackman M. J., Holder A. A. Use of a recombinant baculovirus product to measure naturally-acquired human antibodies to disulphide-constrained epitopes on the P. falciparum merozoite surface protein-1 (MSP1). FEMS Immunol Med Microbiol. 1993 Apr;6(4):307–315. doi: 10.1111/j.1574-695X.1993.tb00343.x. [DOI] [PubMed] [Google Scholar]
- Blackman M. J., Ling I. T., Nicholls S. C., Holder A. A. Proteolytic processing of the Plasmodium falciparum merozoite surface protein-1 produces a membrane-bound fragment containing two epidermal growth factor-like domains. Mol Biochem Parasitol. 1991 Nov;49(1):29–33. doi: 10.1016/0166-6851(91)90127-r. [DOI] [PubMed] [Google Scholar]
- Blackman M. J., Scott-Finnigan T. J., Shai S., Holder A. A. Antibodies inhibit the protease-mediated processing of a malaria merozoite surface protein. J Exp Med. 1994 Jul 1;180(1):389–393. doi: 10.1084/jem.180.1.389. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Blackman M. J., Whittle H., Holder A. A. Processing of the Plasmodium falciparum major merozoite surface protein-1: identification of a 33-kilodalton secondary processing product which is shed prior to erythrocyte invasion. Mol Biochem Parasitol. 1991 Nov;49(1):35–44. doi: 10.1016/0166-6851(91)90128-s. [DOI] [PubMed] [Google Scholar]
- Bouharoun-Tayoun H., Attanath P., Sabchareon A., Chongsuphajaisiddhi T., Druilhe P. Antibodies that protect humans against Plasmodium falciparum blood stages do not on their own inhibit parasite growth and invasion in vitro, but act in cooperation with monocytes. J Exp Med. 1990 Dec 1;172(6):1633–1641. doi: 10.1084/jem.172.6.1633. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Boyle D. B., Newbold C. I., Smith C. C., Brown K. N. Monoclonal antibodies that protect in vivo against Plasmodium chabaudi recognize a 250,000-dalton parasite polypeptide. Infect Immun. 1982 Oct;38(1):94–102. doi: 10.1128/iai.38.1.94-102.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Burghaus P. A., Holder A. A. Expression of the 19-kilodalton carboxy-terminal fragment of the Plasmodium falciparum merozoite surface protein-1 in Escherichia coli as a correctly folded protein. Mol Biochem Parasitol. 1994 Mar;64(1):165–169. doi: 10.1016/0166-6851(94)90144-9. [DOI] [PubMed] [Google Scholar]
- Burns J. M., Jr, Majarian W. R., Young J. F., Daly T. M., Long C. A. A protective monoclonal antibody recognizes an epitope in the carboxyl-terminal cysteine-rich domain in the precursor of the major merozoite surface antigen of the rodent malarial parasite, Plasmodium yoelii. J Immunol. 1989 Oct 15;143(8):2670–2676. [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]
- Chang S. P., Gibson H. L., Lee-Ng C. T., Barr P. J., Hui G. S. A carboxyl-terminal fragment of Plasmodium falciparum gp195 expressed by a recombinant baculovirus induces antibodies that completely inhibit parasite growth. J Immunol. 1992 Jul 15;149(2):548–555. [PubMed] [Google Scholar]
- Chappel J. A., Holder A. A. Monoclonal antibodies that inhibit Plasmodium falciparum invasion in vitro recognise the first growth factor-like domain of merozoite surface protein-1. Mol Biochem Parasitol. 1993 Aug;60(2):303–311. doi: 10.1016/0166-6851(93)90141-j. [DOI] [PubMed] [Google Scholar]
- Cheung A., Leban J., Shaw A. R., Merkli B., Stocker J., Chizzolini C., Sander C., Perrin L. H. Immunization with synthetic peptides of a Plasmodium falciparum surface antigen induces antimerozoite antibodies. Proc Natl Acad Sci U S A. 1986 Nov;83(21):8328–8332. doi: 10.1073/pnas.83.21.8328. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cooper J. A., Cooper L. T., Saul A. J. Mapping of the region predominantly recognized by antibodies to the Plasmodium falciparum merozoite surface antigen MSA 1. Mol Biochem Parasitol. 1992 Apr;51(2):301–312. doi: 10.1016/0166-6851(92)90080-4. [DOI] [PubMed] [Google Scholar]
- Daly T. M., Burns J. M., Jr, Long C. A. Comparison of the carboxy-terminal, cysteine-rich domain of the merozoite surface protein-1 from several strains of Plasmodium yoelii. Mol Biochem Parasitol. 1992 Jun;52(2):279–282. doi: 10.1016/0166-6851(92)90061-n. [DOI] [PubMed] [Google Scholar]
- Daly T. M., Long C. A. A recombinant 15-kilodalton carboxyl-terminal fragment of Plasmodium yoelii yoelii 17XL merozoite surface protein 1 induces a protective immune response in mice. Infect Immun. 1993 Jun;61(6):2462–2467. doi: 10.1128/iai.61.6.2462-2467.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Diggs C. L., Ballou W. R., Miller L. H. The major merozoite surface protein as a malaria vaccine target. Parasitol Today. 1993 Aug;9(8):300–302. doi: 10.1016/0169-4758(93)90130-8. [DOI] [PubMed] [Google Scholar]
- Etlinger H. M., Caspers P., Matile H., Schoenfeld H. J., Stueber D., Takacs B. Ability of recombinant or native proteins to protect monkeys against heterologous challenge with Plasmodium falciparum. Infect Immun. 1991 Oct;59(10):3498–3503. doi: 10.1128/iai.59.10.3498-3503.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hall R., Hyde J. E., Goman M., Simmons D. L., Hope I. A., Mackay M., Scaife J., Merkli B., Richle R., Stocker J. Major surface antigen gene of a human malaria parasite cloned and expressed in bacteria. 1984 Sep 27-Oct 3Nature. 311(5984):379–382. doi: 10.1038/311379a0. [DOI] [PubMed] [Google Scholar]
- Herrera M. A., Rosero F., Herrera S., Caspers P., Rotmann D., Sinigaglia F., Certa U. Protection against malaria in Aotus monkeys immunized with a recombinant blood-stage antigen fused to a universal T-cell epitope: correlation of serum gamma interferon levels with protection. Infect Immun. 1992 Jan;60(1):154–158. doi: 10.1128/iai.60.1.154-158.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Holder A. A., Blackman M. J., Burghaus P. A., Chappel J. A., Ling I. T., McCallum-Deighton N., Shai S. A malaria merozoite surface protein (MSP1)-structure, processing and function. Mem Inst Oswaldo Cruz. 1992;87 (Suppl 3):37–42. doi: 10.1590/s0074-02761992000700004. [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]
- Holder A. A., Freeman R. R., Nicholls S. C. Immunization against Plasmodium falciparum with recombinant polypeptides produced in Escherichia coli. Parasite Immunol. 1988 Nov;10(6):607–617. doi: 10.1111/j.1365-3024.1988.tb00248.x. [DOI] [PubMed] [Google Scholar]
- Holder A. A., Lockyer M. J., Odink K. G., Sandhu J. S., Riveros-Moreno V., Nicholls S. C., Hillman Y., Davey L. S., Tizard M. L., Schwarz R. T. Primary structure of the precursor to the three major surface antigens of Plasmodium falciparum merozoites. Nature. 1985 Sep 19;317(6034):270–273. doi: 10.1038/317270a0. [DOI] [PubMed] [Google Scholar]
- Holder A. A. The precursor to major merozoite surface antigens: structure and role in immunity. Prog Allergy. 1988;41:72–97. [PubMed] [Google Scholar]
- Kaslow D. C., Hui G., Kumar S. Expression and antigenicity of Plasmodium falciparum major merozoite surface protein (MSP1(19)) variants secreted from Saccharomyces cerevisiae. Mol Biochem Parasitol. 1994 Feb;63(2):283–289. doi: 10.1016/0166-6851(94)90064-7. [DOI] [PubMed] [Google Scholar]
- Kemeny D. M. Titration of antibodies. J Immunol Methods. 1992 Jun 24;150(1-2):57–76. doi: 10.1016/0022-1759(92)90065-2. [DOI] [PubMed] [Google Scholar]
- Lew A. M., Langford C. J., Anders R. F., Kemp D. J., Saul A., Fardoulys C., Geysen M., Sheppard M. A protective monoclonal antibody recognizes a linear epitope in the precursor to the major merozoite antigens of Plasmodium chabaudi adami. Proc Natl Acad Sci U S A. 1989 May;86(10):3768–3772. doi: 10.1073/pnas.86.10.3768. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ling I. T., Ogun S. A., Holder A. A. Immunization against malaria with a recombinant protein. Parasite Immunol. 1994 Feb;16(2):63–67. doi: 10.1111/j.1365-3024.1994.tb00324.x. [DOI] [PubMed] [Google Scholar]
- Majarian W. R., Daly T. M., Weidanz W. P., Long C. A. Passive immunization against murine malaria with an IgG3 monoclonal antibody. J Immunol. 1984 Jun;132(6):3131–3137. [PubMed] [Google Scholar]
- McBride J. S., Heidrich H. G. Fragments of the polymorphic Mr 185,000 glycoprotein from the surface of isolated Plasmodium falciparum merozoites form an antigenic complex. Mol Biochem Parasitol. 1987 Feb;23(1):71–84. doi: 10.1016/0166-6851(87)90189-7. [DOI] [PubMed] [Google Scholar]
- McCallum-Deighton N., Holder A. A. The role of calcium in the invasion of human erythrocytes by Plasmodium falciparum. Mol Biochem Parasitol. 1992 Feb;50(2):317–323. doi: 10.1016/0166-6851(92)90229-d. [DOI] [PubMed] [Google Scholar]
- McKean P. G., O'Dea K., Brown K. N. A single amino acid determines the specificity of a monoclonal antibody which inhibits Plasmodium chabaudi AS in vivo. Mol Biochem Parasitol. 1993 Dec;62(2):211–221. doi: 10.1016/0166-6851(93)90110-j. [DOI] [PubMed] [Google Scholar]
- Miller L. H., Roberts T., Shahabuddin M., McCutchan T. F. Analysis of sequence diversity in the Plasmodium falciparum merozoite surface protein-1 (MSP-1). Mol Biochem Parasitol. 1993 May;59(1):1–14. doi: 10.1016/0166-6851(93)90002-f. [DOI] [PubMed] [Google Scholar]
- Murphy V. F., Rowan W. C., Page M. J., Holder A. A. Expression of hybrid malaria antigens in insect cells and their engineering for correct folding and secretion. Parasitology. 1990 Apr;100(Pt 2):177–183. doi: 10.1017/s0031182000061175. [DOI] [PubMed] [Google Scholar]
- Patarroyo M. E., Romero P., Torres M. L., Clavijo P., Moreno A., Martínez A., Rodríguez R., Guzman F., Cabezas E. Induction of protective immunity against experimental infection with malaria using synthetic peptides. Nature. 1987 Aug 13;328(6131):629–632. doi: 10.1038/328629a0. [DOI] [PubMed] [Google Scholar]
- Perrin L. H., Merkli B., Loche M., Chizzolini C., Smart J., Richle R. Antimalarial immunity in Saimiri monkeys. Immunization with surface components of asexual blood stages. J Exp Med. 1984 Aug 1;160(2):441–451. doi: 10.1084/jem.160.2.441. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pirson P. J., Perkins M. E. Characterization with monoclonal antibodies of a surface antigen of Plasmodium falciparum merozoites. J Immunol. 1985 Mar;134(3):1946–1951. [PubMed] [Google Scholar]
- Sabchareon A., Burnouf T., Ouattara D., Attanath P., Bouharoun-Tayoun H., Chantavanich P., Foucault C., Chongsuphajaisiddhi T., Druilhe P. Parasitologic and clinical human response to immunoglobulin administration in falciparum malaria. Am J Trop Med Hyg. 1991 Sep;45(3):297–308. doi: 10.4269/ajtmh.1991.45.297. [DOI] [PubMed] [Google Scholar]
- Saul A. Kinetic constraints on the development of a malaria vaccine. Parasite Immunol. 1987 Jan;9(1):1–9. doi: 10.1111/j.1365-3024.1987.tb00483.x. [DOI] [PubMed] [Google Scholar]
- Schägger H., von Jagow G. Tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis for the separation of proteins in the range from 1 to 100 kDa. Anal Biochem. 1987 Nov 1;166(2):368–379. doi: 10.1016/0003-2697(87)90587-2. [DOI] [PubMed] [Google Scholar]
- Siddiqui W. A., Tam L. Q., Kramer K. J., Hui G. S., Case S. E., Yamaga K. M., Chang S. P., Chan E. B., Kan S. C. Merozoite surface coat precursor protein completely protects Aotus monkeys against Plasmodium falciparum malaria. Proc Natl Acad Sci U S A. 1987 May;84(9):3014–3018. doi: 10.1073/pnas.84.9.3014. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smith D. B., Johnson K. S. Single-step purification of polypeptides expressed in Escherichia coli as fusions with glutathione S-transferase. Gene. 1988 Jul 15;67(1):31–40. doi: 10.1016/0378-1119(88)90005-4. [DOI] [PubMed] [Google Scholar]
- Thaithong S., Beale G. H., Fenton B., McBride J., Rosario V., Walker A., Walliker D. Clonal diversity in a single isolate of the malaria parasite Plasmodium falciparum. Trans R Soc Trop Med Hyg. 1984;78(2):242–245. doi: 10.1016/0035-9203(84)90287-6. [DOI] [PubMed] [Google Scholar]
- Valero M. V., Amador L. R., Galindo C., Figueroa J., Bello M. S., Murillo L. A., Mora A. L., Patarroyo G., Rocha C. L., Rojas M. Vaccination with SPf66, a chemically synthesised vaccine, against Plasmodium falciparum malaria in Colombia. Lancet. 1993 Mar 20;341(8847):705–710. doi: 10.1016/0140-6736(93)90483-w. [DOI] [PubMed] [Google Scholar]
- Wasserman M., Alarcón C., Mendoza P. M. Effects of Ca++ depletion on the asexual cell cycle of Plasmodium falciparum. Am J Trop Med Hyg. 1982 Jul;31(4):711–717. doi: 10.4269/ajtmh.1982.31.711. [DOI] [PubMed] [Google Scholar]
- Wilson C. F., Anand R., Clark J. T., McBride J. S. Topography of epitopes on a polymorphic schizont antigen of Plasmodium falciparum determined by the binding of monoclonal antibodies in a two-site radioimmunoassay. Parasite Immunol. 1987 Nov;9(6):737–746. doi: 10.1111/j.1365-3024.1987.tb00541.x. [DOI] [PubMed] [Google Scholar]