J. Exp. Med., Volume 186, Number 10, November 17, 1997 1689-1699

Antibodies that Inhibit Malaria Merozoite Surface Protein-1 Processing and Erythrocyte Invasion Are Blocked by Naturally Acquired Human Antibodies

By José A. Guevara Patiño,^* Anthony A. Holder,^* Jana S. McBride, and Michael J. Blackman^*

From the ^* Division of Parasitology, National Institute for Medical Research, London NW7 1AA, United Kingdom; and  Institute of Cell, Animal and Population Biology, University of Edinburgh, Ashworth Laboratories, Edinburgh EH9 3JT, United Kingdom

Merozoite surface protein-1 (MSP-1) of the human malaria parasite Plasmodium falciparum undergoes at least two endoproteolytic cleavage events during merozoite maturation and release, and erythrocyte invasion. We have previously demonstrated that mAbs which inhibit erythrocyte invasion and are specific for epitopes within a membrane-proximal, COOH-terminal domain of MSP-1 (MSP-1₁₉) prevent the critical secondary processing step which occurs on the surface of the extracellular merozoite at around the time of erythrocyte invasion. Certain other anti-MSP-1₁₉ mAbs, which themselves inhibit neither erythrocyte invasion nor MSP-1 secondary processing, block the processing-inhibitory activity of the first group of antibodies and are termed blocking antibodies. We have now directly quantitated antibody-mediated inhibition of MSP-1 secondary processing and invasion, and the effects on this of blocking antibodies. We show that blocking antibodies function by competing with the binding of processing-inhibitory antibodies to their epitopes on the merozoite. Polyclonal rabbit antibodies specific for certain MSP-1 sequences outside of MSP-1₁₉ also act as blocking antibodies. Most significantly, affinity-purified, naturally acquired human antibodies specific for epitopes within the NH₂-terminal 83-kD domain of MSP-1 very effectively block the processing-inhibitory activity of the anti-MSP-1₁₉ mAb 12.8. The presence of these blocking antibodies also completely abrogates the inhibitory effect of mAb 12.8 on erythrocyte invasion by the parasite in vitro. Blocking antibodies therefore (a) are part of the human response to malarial infection; (b) can be induced by MSP-1 structures unrelated to the MSP-1₁₉ target of processing-inhibitory antibodies; and (c) have the potential to abolish protection mediated by anti-MSP-1₁₉ antibodies. Our results suggest that an effective MSP-1₁₉-based falciparum malaria vaccine should aim to induce an antibody response that prevents MSP-1 processing on the merozoite surface.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Miura, K., Zhou, H., Moretz, S. E., Diouf, A., Thera, M. A., Dolo, A., Doumbo, O., Malkin, E., Diemert, D., Miller, L. H., Mullen, G. E. D., Long, C. A. (2008). Comparison of Biological Activity of Human Anti-Apical Membrane Antigen-1 Antibodies Induced by Natural Infection and Vaccination. J. Immunol. 181: 8776-8783 [Abstract] [Full Text]  
• Carralot, J.-P., Lemmel, C., Stevanovic, S., Pascolo, S. (2008). Mass spectrometric identification of an HLA-A*0201 epitope from Plasmodium falciparum MSP-1. Int Immunol 20: 1451-1456 [Abstract] [Full Text]  
• Cheng, X.-J., Hayasaka, H., Watanabe, K., Tao, Y.-L., Liu, J.-Y., Tsukamoto, H., Horii, T., Tanabe, K., Tachibana, H. (2007). Production of High-Affinity Human Monoclonal Antibody Fab Fragments to the 19-Kilodalton C-Terminal Merozoite Surface Protein 1 of Plasmodium falciparum. Infect. Immun. 75: 3614-3620 [Abstract] [Full Text]  
• BONILLA, J. A., VALIDUM, L., CUMMINGS, R., PALMER, C. J. (2006). GENETIC DIVERSITY OF PLASMODIUM VIVAX PVCSP AND PVMSP1 IN GUYANA, SOUTH AMERICA. Am J Trop Med Hyg 75: 830-835 [Abstract] [Full Text]  
• Kauth, C. W., Woehlbier, U., Kern, M., Mekonnen, Z., Lutz, R., Mucke, N., Langowski, J., Bujard, H. (2006). Interactions between Merozoite Surface Proteins 1, 6, and 7 of the Malaria Parasite Plasmodium falciparum. J. Biol. Chem. 281: 31517-31527 [Abstract] [Full Text]  
• Persson, K. E. M., Lee, C. T., Marsh, K., Beeson, J. G. (2006). Development and Optimization of High-Throughput Methods To Measure Plasmodium falciparum-Specific Growth Inhibitory Antibodies.. J. Clin. Microbiol. 44: 1665-1673 [Abstract] [Full Text]  
• Woehlbier, U., Epp, C., Kauth, C. W., Lutz, R., Long, C. A., Coulibaly, B., Kouyate, B., Arevalo-Herrera, M., Herrera, S., Bujard, H. (2006). Analysis of Antibodies Directed against Merozoite Surface Protein 1 of the Human Malaria Parasite Plasmodium falciparum. Infect. Immun. 74: 1313-1322 [Abstract] [Full Text]  
• Harris, K. S., Casey, J. L., Coley, A. M., Masciantonio, R., Sabo, J. K., Keizer, D. W., Lee, E. F., McMahon, A., Norton, R. S., Anders, R. F., Foley, M. (2005). Binding Hot Spot for Invasion Inhibitory Molecules on Plasmodium falciparum Apical Membrane Antigen 1. Infect. Immun. 73: 6981-6989 [Abstract] [Full Text]  
• Darko, C. A., Angov, E., Collins, W. E., Bergmann-Leitner, E. S., Girouard, A. S., Hitt, S. L., McBride, J. S., Diggs, C. L., Holder, A. A., Long, C. A., Barnwell, J. W., Lyon, J. A. (2005). The Clinical-Grade 42-Kilodalton Fragment of Merozoite Surface Protein 1 of Plasmodium falciparum Strain FVO Expressed in Escherichia coli Protects Aotus nancymai against Challenge with Homologous Erythrocytic-Stage Parasites. Infect. Immun. 73: 287-297 [Abstract] [Full Text]  
• Lobo, C.-A. (2005). Babesia divergens and Plasmodium falciparum Use Common Receptors, Glycophorins A and B, To Invade the Human Red Blood Cell. Infect. Immun. 73: 649-651 [Abstract] [Full Text]  
• Le Roch, K. G., Johnson, J. R., Florens, L., Zhou, Y., Santrosyan, A., Grainger, M., Yan, S. F., Williamson, K. C., Holder, A. A., Carucci, D. J., Yates, J. R. III, Winzeler, E. A. (2004). Global analysis of transcript and protein levels across the Plasmodium falciparum life cycle. Genome Res 14: 2308-2318 [Abstract] [Full Text]  
• Corran, P. H., O'Donnell, R. A., Todd, J., Uthaipibull, C., Holder, A. A., Crabb, B. S., Riley, E. M. (2004). The Fine Specificity, but Not the Invasion Inhibitory Activity, of 19-Kilodalton Merozoite Surface Protein 1-Specific Antibodies Is Associated with Resistance to Malarial Parasitemia in a Cross-Sectional Survey in The Gambia. Infect. Immun. 72: 6185-6189 [Abstract] [Full Text]  
• John, C. C., O'Donnell, R. A., Sumba, P. O., Moormann, A. M., de Koning-Ward, T. F., King, C. L., Kazura, J. W., Crabb, B. S. (2004). Evidence That Invasion-Inhibitory Antibodies Specific for the 19-kDa Fragment of Merozoite Surface Protein-1 (MSP-119) Can Play a Protective Role against Blood-Stage Plasmodium falciparum Infection in Individuals in a Malaria Endemic Area of Africa. J. Immunol. 173: 666-672 [Abstract] [Full Text]  
• Pan, W., Huang, D., Zhang, Q., Qu, L., Zhang, D., Zhang, X., Xue, X., Qian, F. (2004). Fusion of Two Malaria Vaccine Candidate Antigens Enhances Product Yield, Immunogenicity, and Antibody-Mediated Inhibition of Parasite Growth In Vitro. J. Immunol. 172: 6167-6174 [Abstract] [Full Text]  
• Okech, B. A., Corran, P. H., Todd, J., Joynson-Hicks, A., Uthaipibull, C., Egwang, T. G., Holder, A. A., Riley, E. M. (2004). Fine Specificity of Serum Antibodies to Plasmodium falciparum Merozoite Surface Protein, PfMSP-119, Predicts Protection from Malaria Infection and High-Density Parasitemia. Infect. Immun. 72: 1557-1567 [Abstract] [Full Text]  
• Taylor, D. W., Zhou, A., Marsillio, L. E., Thuita, L. W., Leke, E. B., Branch, O., Gowda, D. C., Long, C., Leke, R. F. G. (2004). Antibodies That Inhibit Binding of Plasmodium falciparum-Infected Erythrocytes to Chondroitin Sulfate A and to the C Terminus of Merozoite Surface Protein 1 Correlate with Reduced Placental Malaria in Cameroonian Women. Infect. Immun. 72: 1603-1607 [Abstract] [Full Text]  
• de Koning-Ward, T. F., O'Donnell, R. A., Drew, D. R., Thomson, R., Speed, T. P., Crabb, B. S. (2003). A New Rodent Model to Assess Blood Stage Immunity to the Plasmodium falciparum Antigen Merozoite Surface Protein 119 Reveals a Protective Role for Invasion Inhibitory Antibodies. JEM 198: 869-875 [Abstract] [Full Text]  
• Chattopadhyay, R., Rathore, D., Fujioka, H., Kumar, S., de la Vega, P., Haynes, D., Moch, K., Fryauff, D., Wang, R., Carucci, D. J., Hoffman, S. L. (2003). PfSPATR, a Plasmodium falciparum Protein Containing an Altered Thrombospondin Type I Repeat Domain Is Expressed at Several Stages of the Parasite Life Cycle and Is the Target of Inhibitory Antibodies. J. Biol. Chem. 278: 25977-25981 [Abstract] [Full Text]  
• Howell, S. A., Well, I., Fleck, S. L., Kettleborough, C., Collins, C. R., Blackman, M. J. (2003). A Single Malaria Merozoite Serine Protease Mediates Shedding of Multiple Surface Proteins by Juxtamembrane Cleavage. J. Biol. Chem. 278: 23890-23898 [Abstract] [Full Text]  
• Kauth, C. W., Epp, C., Bujard, H., Lutz, R. (2003). The Merozoite Surface Protein 1 Complex of Human Malaria Parasite Plasmodium falciparum: INTERACTIONS AND ARRANGEMENTS OF SUBUNITS. J. Biol. Chem. 278: 22257-22264 [Abstract] [Full Text]  
• Garman, S. C., Simcoke, W. N., Stowers, A. W., Garboczi, D. N. (2003). Structure of the C-terminal Domains of Merozoite Surface Protein-1 from Plasmodium knowlesi Reveals a Novel Histidine Binding Site. J. Biol. Chem. 278: 7264-7269 [Abstract] [Full Text]  
• Nyalwidhe, J., Baumeister, S., Hibbs, A. R., Tawill, S., Papakrivos, J., Volker, U., Lingelbach, K. (2002). A Nonpermeant Biotin Derivative Gains Access to the Parasitophorous Vacuole in Plasmodium falciparum-infected Erythrocytes Permeabilized with Streptolysin O. J. Biol. Chem. 277: 40005-40011 [Abstract] [Full Text]  
• Healer, J., Crawford, S., Ralph, S., McFadden, G., Cowman, A. F. (2002). Independent Translocation of Two Micronemal Proteins in Developing Plasmodium falciparum Merozoites. Infect. Immun. 70: 5751-5758 [Abstract] [Full Text]  
• Nwuba, R. I., Sodeinde, O., Anumudu, C. I., Omosun, Y. O., Odaibo, A. B., Holder, A. A., Nwagwu, M. (2002). The Human Immune Response to Plasmodium falciparum Includes Both Antibodies That Inhibit Merozoite Surface Protein 1 Secondary Processing and Blocking Antibodies. Infect. Immun. 70: 5328-5331 [Abstract] [Full Text]  
• Qian, F., Pan, W. (2002). Construction of a tetR-Integrated Salmonella enterica Serovar Typhi CVD908 Strain That Tightly Controls Expression of the Major Merozoite Surface Protein of Plasmodium falciparum for Applications in Human Vaccine Production. Infect. Immun. 70: 2029-2038 [Abstract] [Full Text]  
• Ahlborg, N., Ling, I. T., Howard, W., Holder, A. A., Riley, E. M. (2002). Protective Immune Responses to the 42-Kilodalton (kDa) Region of Plasmodium yoelii Merozoite Surface Protein 1 Are Induced by the C-Terminal 19-kDa Region but Not by the Adjacent 33-kDa Region. Infect. Immun. 70: 820-825 [Abstract] [Full Text]  
• Weatherall, D. J., Miller, L. H., Baruch, D. I., Marsh, K., Doumbo, O. K., Casals-Pascual, C., Roberts, D. J. (2002). Malaria and the Red Cell. ASH Education Book 2002: 35-57 [Abstract] [Full Text]  
• Urban, B. C., Mwangi, T., Ross, A., Kinyanjui, S., Mosobo, M., Kai, O., Lowe, B., Marsh, K., Roberts, D. J. (2001). Peripheral blood dendritic cells in children with acute Plasmodium falciparum malaria. Blood 98: 2859-2861 [Abstract] [Full Text]  
• Coley, A. M., Campanale, N. V., Casey, J. L., Hodder, A. N., Crewther, P. E., Anders, R. F., Tilley, L. M., Foley, M. (2001). Rapid and precise epitope mapping of monoclonal antibodies against Plasmodium falciparum AMA1 by combined phage display of fragments and random peptides. Protein Eng Des Sel 14: 691-698 [Abstract] [Full Text]  
• O'Donnell, R. A., de Koning-Ward, T. F., Burt, R. A., Bockarie, M., Reeder, J. C., Cowman, A. F., Crabb, B. S. (2001). Antibodies Against Merozoite Surface Protein (MSP)-119 Are a Major Component of the Invasion-inhibitory Response in Individuals Immune to Malaria. JEM 193: 1403-1412 [Abstract] [Full Text]  
• Moreno, R., Poltl-Frank, F., Stuber, D., Matile, H., Mutz, M., Weiss, N. A., Pluschke, G. (2001). Rhoptry-Associated Protein 1-Binding Monoclonal Antibody Raised against a Heterologous Peptide Sequence Inhibits Plasmodium falciparum Growth In Vitro. Infect. Immun. 69: 2558-2568 [Abstract] [Full Text]  
• Badell, E., Oeuvray, C., Moreno, A., Soe, S., van Rooijen, N., Bouzidi, A., Druilhe, P. (2000). Human Malaria in Immunocompromised Mice: An In Vivo Model to Study Defense Mechanisms against Plasmodium falciparum. JEM 192: 1653-1660 [Abstract] [Full Text]  
• Ahlborg, N., Ling, I. T., Holder, A. A., Riley, E. M. (2000). Linkage of Exogenous T-cell Epitopes to the 19-Kilodalton Region of Plasmodium yoelii Merozoite Surface Protein 1 (MSP119) Can Enhance Protective Immunity against Malaria and Modulate the Immunoglobulin Subclass Response to MSP119. Infect. Immun. 68: 2102-2109 [Abstract] [Full Text]  
• Kumar, S., Collins, W., Egan, A., Yadava, A., Garraud, O., Blackman, M. J., Patino, J. A. G., Diggs, C., Kaslow, D. C. (2000). Immunogenicity and Efficacy in Aotus Monkeys of Four Recombinant Plasmodium falciparum Vaccines in Multiple Adjuvant Formulations Based on the 19-Kilodalton C Terminus of Merozoite Surface Protein 1. Infect. Immun. 68: 2215-2223 [Abstract] [Full Text]  
• Egan, A. F., Blackman, M. J., Kaslow, D. C. (2000). Vaccine Efficacy of Recombinant Plasmodium falciparum Merozoite Surface Protein 1 in Malaria-Naive, -Exposed, and/or -Rechallenged Aotus vociferans Monkeys. Infect. Immun. 68: 1418-1427 [Abstract] [Full Text]  
• Holder, A. A. (1999). Malaria vaccines. Proc. Natl. Acad. Sci. USA 96: 1167-1169 [Full Text]  
• Ferguson, N., Anderson, R., Gupta, S. (1999). The effect of antibody-dependent enhancement on the transmission dynamics and persistence of multiple-strain pathogens. Proc. Natl. Acad. Sci. USA 96: 790-794 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS