1921
Volume 76, Issue 6
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Parasite genotyping studies have indicated that the populations circulating in Iran are genetically diverse and that multiple genotype infections are observed regularly. We wished to extend the analysis to the gene, coding for the dominant sporozoite surface antigen on which the leading malaria vaccine candidate RTS,S is based. Infected blood samples were collected mainly from Iranian, as well as Afghani and Pakistani, patients on admission with falciparum malaria. DNA was purified from 90 isolates, and from these, 21 fragments corresponding to and 69 fragments corresponding to the 3′-end conserved domain were amplified and sequenced. Overall diversity was low. Six patterns were noted for the repeat region, but mixed genotypes were not observed in any of the isolates. T cell epitopes also displayed limited diversity, with only five haplotypes (combined Th2R/Th3R epitopes) noted, and of these, three were dominant, accounting for 94% of the 90 sequences. These observations are akin to those observed in Thai isolates, where a particular Th2R/Th3R haplotype seems to be maintained in an otherwise genetically diverse parasite population. The data imply that the selective pressure that maintains a restricted T cell epitope is caused by factors outside the mammalian host immune responses. Furthermore, they sustain the notion that protective responses induced by RTS,S vaccination are not strain-specific.

Loading

Article metrics loading...

/content/journals/10.4269/ajtmh.2007.76.1046
2007-06-01
2017-11-17
Loading full text...

Full text loading...

/deliver/fulltext/14761645/76/6/0761046.html?itemId=/content/journals/10.4269/ajtmh.2007.76.1046&mimeType=html&fmt=ahah

References

  1. Marsh K, 1998. Malaria disaster in Africa. Lancet 352 : 924.
  2. Dame JB, Williams JL, McCutchan TF, Weber JL, Wirtz RA, Hockmeyer WT, Maloy WL, Haynes JD, Schneider I, Roberts DR, Sanders GS, Reddy EP, Diggs CL, Miller LH, 1984. Structure of the gene encoding the immunodominant surface antigen on the sporozoite of the human malaria parasite Plasmodium falciparum. Science 225 : 593–599.
  3. Ellis J, Ozaki LS, Gwadz RW, Cochrane AH, Nussenzweig V, Nussenzweig RS, Godson GN, 1983. Cloning and expression in E. coli of the malarial sporozoite surface antigen gene from Plasmodium knowlesi. Nature 302 : 536–538.
  4. Herrington DA, Clyde DF, Losonsky GA, Cortesia MJ, Murphy JR, Davis JR, Baqar S, Felix AM, Heimer EP, Gillessen D, Nardin EH, Nussenzweig RS, Nussenzweig V, Hollingdale MR, Levine MM, 1987. Safety and immunogenicity in man of a synthetic peptide malaria vaccine against Plasmodium falciparum sporozoites. Nature 328 : 257–259.
  5. Gordon DM, McGovern TW, Krzych U, Cohen JC, Schneider I, LaChance R, Heppner DG, Yuan G, Hollingdale M, Slaoui M, et al., 1995. Safety, immunogenicity, and efficacy of a recombinantly produced Plasmodium falciparum circumsporozoite protein-hepatitis B surface antigen subunit vaccine. J Infect Dis 171 : 1576–1585.
  6. Alonso PL, Sacarlal J, Aponte JJ, Leach A, Macete E, Milman J, Mandomando I, Spiessens B, Guinovart C, Espasa M, Bassat Q, Aide P, Ofori-Anyinam O, Navia MM, Corachan S, Ceuppens M, Dubois MC, Demoitie MA, Dubovsky F, Menendez C, Tornieporth N, Ballou WR, Thompson R, Cohen J, 2004. Efficacy of the RTS,S/AS02A vaccine against Plasmodium falciparum infection and disease in young African children: randomised controlled trial. Lancet 364 : 1411–1420.
  7. Bojang KA, Milligan PJM, Pinder M, Vigneron L, Alloueche A, Kester KE, Ballou WR, Conway DJ, Reece WHH, Gothard P, Yamuah L, Delchambre M, Voss G, Greenwood BM, Hill AVS, McAdam KP, Tornieporth N, Cohen JD, Doherty T, 2001. Efficacy of RTS,S/AS02 malaria vaccine against Plasmodium falciparum infection in semi-immune adult men in The Gambia: a randomised trial. Lancet 358 : 1927–1934.
  8. Kester KE, McKinney DA, Tornieporth N, Ockenhouse CF, Heppner DG Jr, Hall BT, Krzych U, Delchambre M, Voss G, Dowler MG, Palensky J, Wittes J, Cohen JD, Ballou WR, 2001. Efficacy of recombinant circumsporozoite protein vaccine regimens against experimental Plasmodium falciparum malaria. J Infect Dis 183 : 640–647.
  9. Snounou G, Grüner AC, Muller-Graf CD, Mazier D, Rénia L, 2005. The Plasmodium sporozoite survives RTS,S vaccination. Trends Parasitol 21 : 456–461.
  10. Good MF, Pombo DJ, Maloy WL, De La Cruz VF, Miller LH, Berzofsky JA, 1988. Parasite polymorphism present within minimal T cell epitopes of Plasmodium falciparum circum-sporozoite protein. J Immunol 140 : 1645–1650.
  11. Good MF, Pombo DJ, Quakyi IA, Riley EM, Houghten RA, Menon A, Alling DW, Berzofsky JA, Miller LH, 1988. Human T-cell recognition of the circumsporozoite protein of Plasmodium falciparum: immunodominant T-cell domains map to the polymorphic regions of the molecule. Proc Natl Acad Sci USA 85 : 1199–1203.
  12. Lockyer MJ, Marsh K, Newbold CI, 1989. Wild isolates of Plasmodium falciparum show extensive polymorphism in T cell epitopes of the circumsporozoite protein. Mol Biochem Parasitol 37 : 275–280.
  13. Alloueche A, Milligan P, Conway DJ, Pinder M, Bojang K, Doherty T, Tornieporth N, Cohen J, Greenwood BM, 2003. Protective efficacy of the RTS,S/AS02 Plasmodium falciparum malaria vaccine is not strain specific. Am J Trop Med Hyg 68 : 97–101.
  14. Enosse S, Dobano C, Quelhas D, Aponte JJ, Lievens M, Leach A, Sacarlal J, Greenwood B, Milman J, Dubovsky F, Cohen J, Thompson R, Ballou WR, Alonso PL, Conway DJ, Sutherland CJ, 2006. RTS,S/AS02A malaria vaccine does not induce parasite CSP T cell epitope selection and reduces multiplicity of infection. PLoS Clin. Trials 1 : e5.
  15. Kumkhaek C, Phra-Ek K, Rénia L, Singhasivanon P, Looareesuwan S, Hirunpetcharat C, White NJ, Brockman A, Grüner AC, Lebrun N, Alloueche A, Nosten F, Khusmith S, Snounou G, 2005. Are extensive T cell epitope polymorphisms in the Plasmodium falciparum circumsporozoite antigen, a leading sporozoite vaccine candidate, selected by immune pressure? J Immunol 175 : 3935–3939.
  16. Kumkhaek C, Phraek K, Singhasivanon P, Looareesuwan S, Hirunpetcharat C, Brockman A, Grüner AC, Lebrun N, Rénia L, Nosten F, Snounou G, Khusmith S, 2004. A survey of the Th2R and Th3R allelic variants in the circumsporozoite protein gene of P. falciparum parasites from western Thailand. Southeast Asian J Trop Med Public Health 35 : 281–287.
  17. Zakeri S, Bereczky S, Naimi P, Pedro Gil J, Djadid ND, Färnert A, Snounou G, Björkman A, 2005. Multiple genotypes of the merozoite surface proteins 1 and 2 in Plasmodium falciparum infections in a hypoendemic area in Iran. Trop Med Int Health 10 : 1060–1064.
  18. Snounou G, Viriyakosol S, Jarra W, Thaithong S, Brown KN, 1993. Identification of the four human malaria parasite species in field samples by the polymerase chain reaction and detection of a high prevalence of mixed infections. Mol Biochem Parasitol 58 : 283–292.
  19. Alloueche A, Silveira H, Conway DJ, Bojang KA, Doherty T, Cohen JD, Pinder M, Greenwood BM, 2000. High-throughput sequence typing of T-cell epitope polymorphisms in Plasmodium falciparum circumsporozoite protein. Mol Biochem Parasitol 106 : 273–282.
  20. De Stricker K, Vuust J, Jepsen S, Oeuvray C, Theisen M, 2000. Conservation and heterogeneity of the glutamate-rich protein (GLURP) among field isolates and laboratory lines of Plasmodium falciparum. Mol Biochem Parasitol 111 : 123–130.
  21. Escalante AA, Grebert HM, Isea R, Goldman IF, Basco LK, Magris M, Biswas S, Kariuki SK, Lal AA, 2002. A study of genetic diversity in the gene encoding the circumsporozoite protein (CSP) of Plasmodium falciparum from different transmission areas—XVI. Asembo Bay Cohort Project. Mol Biochem Parasitol 125 : 83–90.
  22. Bhattacharya PR, 1999. Genetic polymorphism in T-cell epitopes of the circumsporozoite protein of Plasmodium falciparum clones and isolates from India. Trans R Soc Trop Med Hyg 93 : 204–207.
  23. Shi Y-P, Alpers MP, Póvoa MM, Lal AA, 1992. Diversity in the immunodominant determinants of the circumsporozoite protein of Plasmodium falciparum parasites from malaria-endemic regions of Papua New Guinea and Brazil. Am J Trop Med Hyg 47 : 844–851.
  24. Yoshida N, Di Santi SM, Dutra AP, Nussenzweig RS, Nussenzweig V, Enea V, 1990. Plasmodium falciparum: restricted polymorphism of T cell epitopes of the circumsporozoite protein in Brazil. Exp Parasitol 71 : 386–392.
  25. Doolan DL, Saul AJ, Good MF, 1992. Geographically restricted heterogeneity of the Plasmodium falciparum circumsporozoite protein: relevance for vaccine development. Infect Immun 60 : 675–682.
  26. Jongwutiwes S, Tanabe K, Hughes MK, Kanbara H, Hughes AL, 1994. Allelic variation in the circumsporozoite protein of Plasmodium falciparum from Thai field isolates. Am J Trop Med Hyg 51 : 659–668.
  27. Tanabe K, Sakihama N, Kaneko A, 2004. Stable SNPs in malaria antigen genes in isolated populations. Science 303 : 493.
  28. Jalloh A, van Thien H, Ferreira MU, Ohashi J, Matsuoka H, Kanbe T, Kikuchi A, Kawamoto F, 2006. Sequence variation in the T-cell epitopes of the Plasmodium falciparum circum-sporozoite protein among field isolates is temporally stable: a 5-year longitudinal study in southern Vietnam. J Clin Microbiol 44 : 1229–1235.
  29. Weedall GD, Preston BM, Thomas AW, Sutherland CJ, Conway DJ, 2006. Differential evidence of natural selection on two leading sporozoite stage malaria vaccine candidate antigens. Int J Parasitol 37 : 77–85.
http://instance.metastore.ingenta.com/content/journals/10.4269/ajtmh.2007.76.1046
Loading
/content/journals/10.4269/ajtmh.2007.76.1046
Loading

Data & Media loading...

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error