Volume 80, Issue 2
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645


Duffy binding protein (DBP) is vital for parasite development, thereby making this molecule a good vaccine candidate. Preclinical development of a vaccine often involves use of primate models prior to testing efficacy in humans, but primate isolates are poorly characterized. We analyzed the complete gene coding for the DBP in several isolates that are used for experimental primate infections and compared these sequences with the Salvador I DBP isolate, which is being used for vaccine development. Our results affirm that primate-adapted isolates are genetically similar to circulating in humans, but variability is greatest in the putative target of protective antibodies. In addition, some isolates contain multiple genetically different clones. Testing a DBP vaccine may therefore be complicated by heterogeneity and diversity of the isolates available for challenge.


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  1. Mendis K, Sina BJ, Marchesini P, Carter R, 2001. The neglected burden of Plasmodium vivax malaria. Am J Trop Med Hyg 64 : 97–106. [Google Scholar]
  2. Chitnis CE, 2001. Molecular insights into receptors used by malaria parasites for erythrocyte invasion. Curr Opin Hematol 8 : 85–91. [Google Scholar]
  3. Adams JH, Sim BKL, Dolan SA, Fang X, Kaslow DC, Miller LH, 1992. A family of erythrocyte binding proteins of malaria parasites. Proc Natl Acad Sci USA 89 : 7085–7089. [Google Scholar]
  4. Barnwell JW, Wertheimer SP, 1989. Plasmodium vivax: merozoite antigens, the Duffy blood group, and erythrocyte invasion. Prog Clin Biol Res 313 : 1–11. [Google Scholar]
  5. Miller LH, Mason SJ, Clyde DF, McGinniss MH, 1976. The resistance factor to Plasmodium vivax in blacks. The Duffy-blood-group genotype, FyFy. N Engl J Med 295 : 302–304. [Google Scholar]
  6. Chitnis CE, Chaudhuri A, Horuk R, Pogo AO, Miller LH, 1996. The domain on the Duffy blood group antigen for binding Plasmodium vivax and P. knowlesi malarial parasites to erythrocytes. J Exp Med 184 : 1531–1536. [Google Scholar]
  7. Vanbuskirk KM, Sevova E, Adams JH, 2004. Conserved residues in the Plasmodium vivax Duffy-binding protein ligand domain are critical for erythrocyte receptor recognition. Proc Natl Acad Sci USA 101 : 15754–15759. [Google Scholar]
  8. Ranjan A, Chitnis CE, 1999. Mapping regions containing binding residues within functional domains of Plasmodium vivax and Plasmodium knowlesi erythrocyte-binding proteins. Proc Natl Acad Sci USA 96 : 14067–14072. [Google Scholar]
  9. Tsuboi T, Kappe SH, al-Yaman F, Prickett MD, Alpers M, Adams JH, 1994. Natural variation within the principal adhesion domain of the Plasmodium vivax Duffy binding protein. Infect Immun 62 : 5581–5586. [Google Scholar]
  10. Ampudia E, Patarroyo MA, Patarroyo ME, Murillo LA, 1996. Genetic polymorphism of the Duffy receptor binding domain of Plasmodium vivax in Colombian wild isolates. Mol Biochem Parasitol 78 : 269–272. [Google Scholar]
  11. Cole-Tobian JL, Cortes A, Baisor M, Kastens W, Xainli J, Bockarie M, Adams JH, King CL, 2002. Age-acquired immunity to a Plasmodium vivax invasion ligand, the Duffy binding protein. J Infect Dis 186 : 531–539. [Google Scholar]
  12. Collins WE, Contacos PG, Krotoski WA, Howard WA, 1972. Transmission of four Central American strains of Plasmodium vivax from monkey to man. J Parasitol 58 : 332–335. [Google Scholar]
  13. Barnwell JW, Nichols ME, Rubinstein P, 1989. In vitro evaluation of the role of the Duffy blood group in erythrocyte invasion by Plasmodium vivax. J Exp Med 169 : 1795–1802. [Google Scholar]
  14. Wertheimer SP, Barnwell JW, 1989. Plasmodium vivax interaction with the human Duffy blood group glycoprotein: identification of a parasite receptor-like protein. Exp Parasitol 69 : 340–350. [Google Scholar]
  15. Cole-Tobian J, King CL, 2003. Diversity and natural selection in Plasmodium vivax Duffy binding protein gene. Mol Biochem Parasitol 127 : 121–132. [Google Scholar]
  16. Nei M, 1987. Molecular Evolutionary Genetics. New York: Columbia University Press.
  17. Saitou N, Nei M, 1987. The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol 4 : 406–425. [Google Scholar]
  18. Xainli J, Adams JH, King CL, 2000. The erythrocyte binding motif of Plasmodium vivax Duffy binding protein is highly polymorphic and functionally conserved in isolates from Papua New Guinea. Mol Biochem Parasitol 111 : 253–260. [Google Scholar]
  19. Thera MA, Doumbo OK, Coulibaly D, Diallo DA, Kone AK, Guindo AB, Traore K, Dicko A, Sagara I, Sissoko MS, Baby M, Sissoko M, Diarra I, Niangaly A, Dolo A, Daou M, Diawara SI, Heppner DG, Stewart VA, Angov E, Bergmann-Leitner ES, Lanar DE, Dutta S, Soisson L, Diggs CL, Leach A, Owusu A, Dubois MC, Cohen J, Nixon JN, Gregson A, Takala SL, Lyke KE, Plowe CV, 2008. Safety and immunogenicity of an AMA-1 malaria vaccine in Malian adults: results of a phase 1 randomized controlled trial. PLoS One 3 : e1465. [Google Scholar]
  20. Polhemus ME, Magill AJ, Cummings JF, Kester KE, Ockenhouse CF, Lanar DE, Dutta S, Barbosa A, Soisson L, Diggs CL, Robinson SA, Haynes JD, Stewart VA, Ware LA, Brando C, Krzych U, Bowden RA, Cohen JD, Dubois MC, Ofori-Anyinam O, De-Kock E, Ballou WR, Heppner DG Jr, 2007. Phase I dose escalation safety and immunogenicity trial of Plasmodium falciparum apical membrane protein (AMA-1) FMP2.1, adjuvanted with AS02A, in malaria-naive adults at the Walter Reed Army Institute of Research. Vaccine 25 : 4203–4212. [Google Scholar]
  21. Ozwara H, Kocken CH, Conway DJ, Mwenda JM, Thomas AW, 2001. Comparative analysis of Plasmodium reichenowi and P. falciparum erythrocyte-binding proteins reveals selection to maintain polymorphism in the erythrocyte-binding region of EBA-175. Mol Biochem Parasitol 116 : 81–84. [Google Scholar]
  22. Baum J, Thomas AW, Conway DJ, 2003. Evidence for diversifying selection on erythrocyte-binding antigens of Plasmodium falciparum and P. vivax. Genetics 163 : 1327–1336. [Google Scholar]
  23. Wilson IA, Cox NJ, 1990. Structural basis of immune recognition of influenza virus hemagglutinin. Annu Rev Immunol 8 : 737–771. [Google Scholar]
  24. Mamillapalli A, Pattnaik P, Sharma M, Sharma SK, Tyagi PK, Joshi H, Chitnis CE, 2006. Sequence polymorphisms in the receptor-binding domain of Plasmodium falciparum EBA-175: implications for malaria vaccine development. Mol Biochem Parasitol 146 : 120–123. [Google Scholar]
  25. Polley SD, Conway DJ, 2001. Strong diversifying selection on domains of the Plasmodium falciparum apical membrane antigen 1 gene. Genetics 158 : 1505–1512. [Google Scholar]
  26. Jongwutiwes S, Putaporntip C, Iwasaki T, Sata T, Kanbara H, 2004. Naturally acquired Plasmodium knowlesi malaria in human, Thailand. Emerg Infect Dis 10 : 2211–2213. [Google Scholar]
  27. Cox-Singh J, Davis TM, Lee KS, Shamsul SS, Matusop A, Ratnam S, Rahman HA, Conway DJ, Singh B, 2008. Plasmodium knowlesi malaria in humans is widely distributed and potentially life threatening. Clin Infect Dis 46 : 165–171. [Google Scholar]
  28. Schmidt LH, Greenland R, Rossan R, Genther C, 1961. Natural occurrence of malaria in rhesus monkeys. Science 133 : 753. [Google Scholar]
  29. Most H, 1973. Plasmodium cynomolgi malaria: accidental human infection. Am J Trop Med Hyg 22 : 157–158. [Google Scholar]
  30. Singh SK, Singh AP, Pandey S, Yazdani SS, Chitnis CE, Sharma A, 2003. Definition of structural elements in Plasmodium vivax and P. knowlesi Duffy-binding domains necessary for erythrocyte invasion. Biochem J 374 : 193–198. [Google Scholar]
  31. Singh SK, Hora R, Belrhali H, Chitnis CE, Sharma A, 2006. Structural basis for Duffy recognition by the malaria parasite Duffy-binding-like domain. Nature 439 : 741–744. [Google Scholar]
  32. Howell DP, Levin EA, Springer AL, Kraemer SM, Phippard DJ, Schief WR, Smith JD, 2008. Mapping a common interaction site used by Plasmodium falciparum Duffy binding-like domains to bind diverse host receptors. Mol Microbiol 67 : 78–87. [Google Scholar]
  33. Dahlback M, Rask TS, Andersen PH, Nielsen MA, Ndam NT, Resende M, Turner L, Deloron P, Hviid L, Lund O, Pedersen AG, Theander TG, Salanti A, 2006. Epitope mapping and topographic analysis of VAR2CSA DBL3X involved in P. falciparum placental sequestration. PLoS Pathog 2 : e124. [Google Scholar]
  34. McHenry AM, Adams JH, 2006. The crystal structure of P. knowlesi DBPalpha DBL domain and its implications for immune evasion. Trends Biochem Sci 31 : 487–491. [Google Scholar]
  35. Vanbuskirk KM, Cole-Tobian JL, Baisor M, Sevova ES, Bockarie M, King CL, Adams JH, 2004. Antigenic drift in the ligand domain of Plasmodium vivax Duffy binding protein confers resistance to inhibitory antibodies. J Infect Dis 190 : 1556–1562. [Google Scholar]
  36. Kain KC, Brown AE, Webster HK, Wirtz RA, Keystone JS, Rodriguez MH, Kinahan J, Rowland M, Lanar DE, 1992. Circumsporozoite genotyping of global isolates of Plasmodium vivax from dried blood specimens. J Clin Microbiol 30 : 1863–1866. [Google Scholar]
  37. Rosenberg R, Wirtz RA, Lanar DE, Sattabongkot J, Hall T, Waters AP, Prasittisuk C, 1989. Circumsporozoite protein heterogeneity in the human malaria parasite Plasmodium vivax. Science 245 : 973–976. [Google Scholar]
  38. Lim CS, Tazi L, Ayala FJ, 2005. Plasmodium vivax: recent world expansion and genetic identity to Plasmodium simium. Proc Natl Acad Sci USA 102 : 15523–15528. [Google Scholar]
  39. Narum DL, Ogun SA, Thomas AW, Holder AA, 2000. Immunization with parasite-derived apical membrane antigen 1 or passive immunization with a specific monoclonalantibody protects BALB/c mice against lethal Plasmodium yoelii yoelii YM blood-stage infection. Infect Immun 68 : 2899–2906. [Google Scholar]
  40. Tamura K, Nei M, Kumar S, 2004. Prospects for inferring very large phylogenies by using the neighbor-joining method. Proc Natl Acad Sci USA 101 : 11030–11035. [Google Scholar]
  41. Tamura K, Dudley J, Nei M, Kumar S, 2007. MEGA4: molecular evolutionary genetics analysis (MEGA) software version 4.0. Mol Biol Evol 24 : 1596–1599. [Google Scholar]

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  • Received : 09 Sep 2008
  • Accepted : 24 Sep 2008

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