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Expression of Plasmodium falciparum 3D7 STEVOR proteins for evaluation of antibody responses following malaria infections in naïve infants

Published online by Cambridge University Press:  12 October 2007

N. SCHREIBER ,
A. KHATTAB ,
M. PETTER ,
F. MARKS ,
S. ADJEI ,
R. KOBBE ,
J. MAY  and
M.-Q. KLINKERT
N. SCHREIBER
Affiliation:
Infectious Disease Epidemiology Group, Bernhard-Nocht Institute for Tropical Medicine, Bernhard-Nocht-Strasse 74, 20359 Hamburg, Germany
A. KHATTAB
Affiliation:
Department of Molecular Medicine, Bernhard-Nocht Institute for Tropical Medicine, Bernhard-Nocht-Strasse 74, 20359 Hamburg, Germany
M. PETTER
Affiliation:
Department of Molecular Medicine, Bernhard-Nocht Institute for Tropical Medicine, Bernhard-Nocht-Strasse 74, 20359 Hamburg, Germany
F. MARKS
Affiliation:
Infectious Disease Epidemiology Group, Bernhard-Nocht Institute for Tropical Medicine, Bernhard-Nocht-Strasse 74, 20359 Hamburg, Germany International Vaccine Institute, Kwanak PO Box 14, Seoul 151-600, South Korea
S. ADJEI
Affiliation:
Kumasi Centre for Collaborative Research in Tropical Medicine, KNUST University Post Office, Kumasi, Ghana
R. KOBBE
Affiliation:
Infectious Disease Epidemiology Group, Bernhard-Nocht Institute for Tropical Medicine, Bernhard-Nocht-Strasse 74, 20359 Hamburg, Germany
J. MAY
Affiliation:
Infectious Disease Epidemiology Group, Bernhard-Nocht Institute for Tropical Medicine, Bernhard-Nocht-Strasse 74, 20359 Hamburg, Germany
M.-Q. KLINKERT*
Affiliation:
Department of Molecular Medicine, Bernhard-Nocht Institute for Tropical Medicine, Bernhard-Nocht-Strasse 74, 20359 Hamburg, Germany
*
*Corresponding author: Bernhard Nocht Institute for Tropical Medicine, Bernhard-Nocht-Strasse 74, 20359 Hamburg, Germany. Tel: +49 40 42818301. Fax: +49 40 42818400. E-mail: mo.klinkert@bni-hamburg.de
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Summary

Clinical immunity to Plasmodium falciparum malaria develops after repeated exposure to the parasite. At least 2 P. falciparum variant antigens encoded by multicopy gene families (var and rif) are targets of this adaptive antibody-mediated immunity. A third multigene family of variant antigens comprises the stevor genes. Here, 4 different stevor sequences were selected for cloning and expression in Escherichia coli and His6–tagged fusion proteins were used for assessing the development of immunity. In a cross-sectional analysis of clinically immune adults living in a malaria endemic area in Ghana, high levels of anti-STEVOR IgG antibody titres were determined in ELISA. A cross-sectional study of 90 nine-month-old Ghanaian infants using 1 recombinant STEVOR showed that the antibody responses correlated positively with the number of parasitaemia episodes. In a longitudinal investigation of 17 immunologically naïve 9-month-old infants, 3 different patterns of anti-STEVOR antibody responses could be distinguished (high, transient and low). Children with high anti-STEVOR-antibody levels exhibited an elevated risk for developing parasitaemia episodes. Overall, a protective effect could not be attributed to antibodies against the STEVOR proteins chosen for the study presented here.

Keywords

recombinant STEVORPlasmodium falciparumimmune responsesinfants
Type
Research Article
Information
Parasitology , Volume 135 , Issue 2 , February 2008 , pp. 155 - 167
Copyright
Copyright © Cambridge University Press 2007

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References

Abdel-Latif, M. S., Dietz, K., Issifou, S., Kremsner, P. G. and Klinkert, M.-Q. (2003). Antibodies to Plasmodium falciparum rifin proteins are associated with rapid parasite clearance and asymptomatic infections. Infection and Immunity 71, 6229–6233.Google Scholar
Abdel-Latif, M. S., Khattab, A., Lindenthal, C., Kremsner, P. G. and Klinkert, M.-Q. (2002). Recognition of variant Rifin antigens by human antibodies induced during natural Plasmodium falciparum infections. Infection and Immunity 70, 7013–7021.Google Scholar
Ahuja, S., Pettersson, F., Moll, K., Jonsson, C., Wahlgren, M. and Chen, Q. (2006). Induction of cross-reactive immune responses to NTS-DBL-1alpha/x of PfEMP1 and in vivo protection on challenge with Plasmodium falciparum. Vaccine 24, 6140–6154.Google Scholar
Beck, H. P., Felger, I., Huber, W., Steiger, S., Smith, T., Weiss, N., Alonso, P. and Tanner, M. (1997). Analysis of multiple Plasmodium falciparum infections in Tanzanian children during the phase III trial of the malaria vaccine SPf66. The Journal of Infectious Diseases 175, 921–926.CrossRefGoogle ScholarPubMed
Belizario, V. Y., Saul, A., Bustos, M. D., Lansang, M. A., Pasay, C. J., Gatton, M. and Salazar, N. P. (1997). Field epidemiological studies on malaria in a low endemic area in the Philippines. Acta Tropica 63, 241–256.Google Scholar
Blythe, J. E., Surentheran, T. and Preiser, P. R. (2004). STEVOR–a multifunctional protein? Molecular and Biochemical Parasitology 134, 11–15.Google Scholar
Bozdech, Z., Zhu, J., Joachimiak, M. P., Cohen, F. E., Pulliam, B. and DeRisi, J. L. (2003). Expression profiling of the schizont and trophozoite stages of Plasmodium falciparum with a long-oligonucleotide microarray. Genome Biology 4, R9.CrossRefGoogle ScholarPubMed
Bull, P. C., Lowe, B. S., Kortok, M., Molyneux, C. S., Newbold, C. I. and Marsh, K. (1998). Parasite antigens on the infected red cell surface are targets for naturally acquired immunity to malaria. Nature Medicine 4, 358–360.Google Scholar
Bull, P. C., Pain, A., Ndungu, F. M., Kinyanjui, S. M., Roberts, D. J., Newbold, C. I. and Marsh, K. (2005). Plasmodium falciparum antigenic variation: relationships between in vivo selection, acquired antibody response, and disease severity. The Journal of Infectious Diseases 192, 1119–1126.Google Scholar
Cabrera, G., Cot, M., Migot-Nabias, F., Kremsner, P. G., Deloron, P. and Luty, A. J. (2005). The sickle cell trait is associated with enhanced immunoglobulin G antibody responses to Plasmodium falciparum variant surface antigens. The Journal of Infectious Diseases 191, 1631–1638.CrossRefGoogle ScholarPubMed
Cheng, Q., Cloonan, N., Fischer, K., Thompson, J., Waine, G., Lanzer, M. and Saul, A. (1998). Stevor and rif are Plasmodium falciparum multicopy gene families which potentially encode variant antigens. Molecular and Biochemical Parasitology 97, 161–176.Google Scholar
Dzikowski, R., Templeton, T. J. and Deitsch, K. (2006). Variant antigen gene expression in malaria. Cellular Microbiology 8, 1371–1381.CrossRefGoogle ScholarPubMed
Fernandez, V., Hommel, M., Chen, Q., Hagblom, P. and Wahlgren, M. (1999). Small, clonally variant antigens expressed on the surface of the Plasmodium falciparum-infected erythrocyte are encoded by the rif gene family and are the target of human immune responses. The Journal of Experimental Medicine 190, 1393–1404.CrossRefGoogle ScholarPubMed
Florens, L., Washburn, M. P., Raine, J. D., Anthony, R. M., Grainger, M., Haynes, J. D., Moch, J. K., Muster, N., Sacci, J. B., Tabb, D. L., Witney, A. A., Wolters, D., Wu, Y., Gardner, M. J., Holder, A. A., Sinden, R. E., Yates, J. R. and Carucci, D. J. (2002). A proteomic view of the Plasmodium falciparum life cycle. Nature, London 419, 520–526.Google Scholar
Garcia, J. E., Puentes, A., Curtidor, H., Vera, R., Rodriguez, L., Valbuena, J., Lopez, R., Ocampo, M., Cortes, J., Vanegas, M., Rosas, J., Reyes, C. and Patarroyo, M. E. (2005). Peptides from the Plasmodium falciparum STEVOR putative protein bind with high affinity to normal human red blood cells. Peptides 26, 1133–1143.CrossRefGoogle ScholarPubMed
Girard, M. P., Reed, Z. H., Friede, M. and Kieny, M. P. (2007). A review of human vaccine research and development: malaria. Vaccine 25, 1567–1580.CrossRefGoogle ScholarPubMed
Helmby, H., Cavelier, L., Pettersson, U. and Wahlgren, M. (1993). Rosetting Plasmodium falciparum-infected erythrocytes express unique strain-specific antigens on their surface. Infection and Immunity 61, 284–288.CrossRefGoogle ScholarPubMed
Kaviratne, M., Khan, S. M., Jarra, W. and Preiser, P. R. (2002). Small variant STEVOR antigen is uniquely located within Maurer's clefts in Plasmodium falciparum-infected red blood cells. Eukaryotic Cell 1, 926–935.Google Scholar
Khattab, A., Reinhardt, C., Staalsoe, T., Fievet, N., Kremsner, P. G., Deloron, P., Hviid, L. and Klinkert, M.-Q. (2004). Analysis of IgG with specificity for variant surface antigens expressed by placental Plasmodium falciparum isolates. Malaria Journal 3, 21.CrossRefGoogle ScholarPubMed
Kobbe, R., Kreuzberg, C., Adjei, S., Thompson, B., Langefeld, I., Thompson, P. A., Abruquah, H. H., Kreuels, B., Ayim, M., Busch, W., Marks, F., Amoah, K., Opoku, E., Meyer, C. G., Adjei, O. and May, J. (2007). A randomised controlled trial of extended intermittent preventive antimalarial treatment in infants. Clinical Infectious Diseases 45, 16–25.CrossRefGoogle ScholarPubMed
Kobbe, R., Neuhoff, R., Marks, F., Adjei, S., Langefeld, I., von Reden, C., Adjei, O., Meyer, C. G. and May, J. (2006). Seasonal variation and high multiplicity of first Plasmodium falciparum infections in children from a holoendemic area in Ghana, West Africa. Tropical Medicine and International Health 11, 613–619.Google Scholar
Lavazec, C., Sanyal, S. and Templeton, T. J. (2006). Hypervariability within the Rifin, Stevor and Pfmc-2TM superfamilies in Plasmodium falciparum. Nucleic Acids Research 34, 6696–6707.CrossRefGoogle ScholarPubMed
Lavazec, C., Sanyal, S. and Templeton, T. J. (2007). Expression switching in the stevor and Pfmc-2TM superfamilies in Plasmodium falciparum. Molecular Microbiology 64, 1621–1634.Google Scholar
Le Roch, K. G., Zhou, Y., Blair, P. L., Grainger, M., Moch, J. K., Haynes, J. D., De La Vega, P., Holder, A. A., Batalov, S., Carucci, D. J. and Winzeler, E. A. (2003). Discovery of gene function by expression profiling of the malaria parasite life cycle. Science 301, 1503–1508.Google Scholar
Lindenthal, C., Kremsner, P. G. and Klinkert, M.-Q. (2003). Commonly recognised Plasmodium falciparum parasites cause cerebral malaria. Parasitology Research 91, 363–368.Google Scholar
Ljungström, I., Perlmann, H., Schlichtherle, M., Scherf, A. and Wahlgren, A. (2004). Methods in Malaria Research. Malaria Research and Reference Reagent Resource Center (MR4).Google Scholar
Llinas, M., Bozdech, Z., Wong, E. D., Adai, A. T. and DeRisi, J. L. (2006). Comparative whole genome transcriptome analysis of three Plasmodium falciparum strains. Nucleic Acids Research 34, 1166–1173.CrossRefGoogle ScholarPubMed
McRobert, L., Preiser, P., Sharp, S., Jarra, W., Kaviratne, M., Taylor, M. C., Renia, L. and Sutherland, C. J. (2004). Distinct trafficking and localization of STEVOR proteins in three stages of the Plasmodium falciparum life cycle. Infection and Immunity 72, 6597–6602.CrossRefGoogle ScholarPubMed
Molineaux, L. and Gramiccia, G. (1980). The Garki Project, World Health Organization, Geneva, Switzerland.Google Scholar
Newton, P., Suputtamongkol, Y., Teja-Isavadharm, P., Pukrittayakamee, S., Navaratnam, V., Bates, I. and White, N. (2000). Antimalarial bioavailability and disposition of artesunate in acute falciparum malaria. Antimicrobial Agents and Chemotherapy 44, 972–977.CrossRefGoogle ScholarPubMed
Ofori, M. F., Dodoo, D., Staalsoe, T., Kurtzhals, J. A., Koram, K., Theander, T. G., Akanmori, B. D. and Hviid, L. (2002). Malaria-induced acquisition of antibodies to Plasmodium falciparum variant surface antigens. Infection and Immunity 70, 2982–2988.Google Scholar
Przyborski, J. M., Miller, S. K., Pfahler, J. M., Henrich, P. P., Rohrbach, P., Crabb, B. S. and Lanzer, M. (2005). Trafficking of STEVOR to the Maurer's clefts in Plasmodium falciparum-infected erythrocytes. European Molecular Biology Organization 24, 2306–2317.CrossRefGoogle Scholar
Recker, M., Nee, S., Bull, P. C., Kinyanjui, S., Marsh, K., Newbold, C. and Gupta, S. (2004). Transient cross-reactive immune responses can orchestrate antigenic variation in malaria. Nature, London 429, 555–558.Google Scholar
Roberts, D. J., Craig, A. G., Berendt, A. R., Pinches, R., Nash, G., Marsh, K. and Newbold, C. I. (1992). Rapid switching to multiple antigenic and adhesive phenotypes in malaria. Nature, London 357, 689–692.Google Scholar
Schreiber, N., Brattig, N., Evans, J., Tsiri, A., Horstmann, R. D., May, J. and Klinkert, M.-Q. (2006). Cerebral malaria is associated with IgG2 and IgG4 antibody responses to recombinant Plasmodium falciparum RIFIN antigen. Microbes and Infection 8, 1269–1276.CrossRefGoogle ScholarPubMed
Sharp, S., Lavstsen, T., Fivelman, Q. L., Saeed, M., McRobert, L., Templeton, T. J., Jensen, A. T., Baker, D. A., Theander, T. G. and Sutherland, C. J. (2006). Programmed transcription of the var gene family, but not of stevor, in Plasmodium falciparum gametocytes. Eukaryotic Cell 5, 1206–1214.CrossRefGoogle Scholar
Su, X. Z., Heatwole, V. M., Wertheimer, S. P., Guinet, F., Herrfeldt, J. A., Peterson, D. S., Ravetch, J. A. and Wellems, T. E. (1995). The large diverse gene family var encodes proteins involved in cytoadherence and antigenic variation of Plasmodium falciparum-infected erythrocytes. Cell 82, 89–100.Google Scholar
Sutherland, C. J. (2001). Stevor transcripts from Plasmodium falciparum gametocytes encode truncated polypeptides. Molecular and Biochemical Parasitology 113, 331–335.Google Scholar
Winstanley, P., Edwards, G., Orme, M. and Breckenridge, A. (1987). The disposition of amodiaquine in man after oral administration. British Journal of Clinical Pharmacology 23, 1–7.Google Scholar