A polyvalent hybrid protein elicits antibodies against the diverse allelic types of block 2 in Plasmodium falciparum merozoite surface protein 1.

Kevin K A Tetteh, David J Conway
Author Information
  1. Kevin K A Tetteh: Department of Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK. kevin.tetteh@lshtm.ac.uk

Abstract

Merozoite surface protein 1 (MSP1) of Plasmodium falciparum has been implicated as an important target of acquired immunity, and candidate components for a vaccine include polymorphic epitopes in the N-terminal polymorphic block 2 region. We designed a polyvalent hybrid recombinant protein incorporating sequences of the three major allelic types of block 2 together with a composite repeat sequence of one of the types and N-terminal flanking T cell epitopes, and compared this with a series of recombinant proteins containing modular sub-components and similarly expressed in Escherichia coli. Immunogenicity of the full polyvalent hybrid protein was tested in both mice and rabbits, and comparative immunogenicity studies of the sub-component modules were performed in mice. The full hybrid protein induced high titre antibodies against each of the major block 2 allelic types expressed as separate recombinant proteins and against a wide range of allelic types naturally expressed by a panel of diverse P. falciparum isolates, while the sub-component modules had partial antigenic coverage as expected. This encourages further development and evaluation of the full MSP1 block 2 polyvalent hybrid protein as a candidate blood-stage component of a malaria vaccine.

References

  1. J Infect Dis. 2002 Mar 1;185(5):657-64 [PMID: 11865423]
  2. Infect Immun. 2010 Feb;78(2):872-83 [PMID: 19933832]
  3. Sci Transl Med. 2009 Oct 14;1(2):2ra5 [PMID: 20165550]
  4. Scand J Immunol Suppl. 1992;11:9-16 [PMID: 1381110]
  5. PLoS Pathog. 2005 Nov;1(3):241-51 [PMID: 16322767]
  6. Infect Immun. 2005 Sep;73(9):5928-35 [PMID: 16113313]
  7. Nat Med. 2000 Jun;6(6):689-92 [PMID: 10835687]
  8. Infect Immun. 2004 Nov;72(11):6492-502 [PMID: 15501780]
  9. Infect Immun. 1996 Jul;64(7):2602-8 [PMID: 8698485]
  10. Trans R Soc Trop Med Hyg. 2004 May;98(5):284-9 [PMID: 15109551]
  11. Nat Med. 2000 Jan;6(1):91-5 [PMID: 10613831]
  12. Vaccine. 2008 Dec 9;26(52):6864-73 [PMID: 18930094]
  13. PLoS One. 2011;6(6):e20977 [PMID: 21698193]
  14. Mol Microbiol. 2008 Apr;68(1):124-38 [PMID: 18333885]
  15. Mol Microbiol. 2010 Oct;78(1):187-202 [PMID: 20735778]
  16. Infect Immun. 2001 Mar;69(3):1536-46 [PMID: 11179324]
  17. Vaccine. 2010 Oct 18;28(44):7167-78 [PMID: 20937436]
  18. BMC Microbiol. 2009 Oct 15;9:219 [PMID: 19832989]
  19. Infect Genet Evol. 2006 Sep;6(5):417-24 [PMID: 16517218]
  20. PLoS One. 2010 Nov 03;5(11):e15391 [PMID: 21082025]
  21. Infect Genet Evol. 2007 Jan;7(1):44-51 [PMID: 16647307]
  22. Trends Parasitol. 2010 Jul;26(7):363-9 [PMID: 20466591]
  23. Mol Biochem Parasitol. 1997 Apr;85(2):197-211 [PMID: 9106193]
  24. PLoS One. 2009 Dec 03;4(12):e8138 [PMID: 19997632]
  25. Vaccine. 2011 Apr 12;29(17):3093-5 [PMID: 21296116]
  26. Infect Immun. 2002 Dec;70(12):6948-60 [PMID: 12438374]
  27. Exp Parasitol. 1996 Oct;84(1):74-83 [PMID: 8888734]
  28. Parasitology. 2009 Oct;136(12):1445-56 [PMID: 19627632]
  29. Malar J. 2010 Mar 18;9:77 [PMID: 20298576]
  30. Infect Immun. 2008 May;76(5):2240-8 [PMID: 18316390]
  31. Infect Immun. 2000 May;68(5):2685-91 [PMID: 10768960]
  32. J Exp Med. 2003 Sep 15;198(6):869-75 [PMID: 12963693]
  33. Infect Immun. 2007 Dec;75(12):5947-55 [PMID: 17938224]
  34. J Infect Dis. 2001 Jan 15;183(2):303-312 [PMID: 11110648]
  35. J Infect Dis. 2009 Apr 15;199(8):1151-4 [PMID: 19284307]
  36. Int Immunol. 1997 Apr;9(4):523-31 [PMID: 9138012]
  37. Infect Immun. 2008 Jun;76(6):2660-70 [PMID: 18378635]
  38. Infect Immun. 2010 Feb;78(2):737-45 [PMID: 19917712]
  39. Parasitology. 2009 Oct;136(12):1435-44 [PMID: 19646305]
  40. J Infect Dis. 2002 Mar 15;185(6):820-7 [PMID: 11920300]
  41. Proc Natl Acad Sci U S A. 2010 Aug 10;107(32):14378-83 [PMID: 20660744]
  42. Infect Immun. 2003 Apr;71(4):1833-42 [PMID: 12654798]
  43. PLoS Clin Trials. 2006 May;1(1):e5 [PMID: 16871327]
  44. Mol Biochem Parasitol. 1993 May;59(1):1-14 [PMID: 8515771]

Grants

  1. /Wellcome Trust

MeSH Term

Animals
Antibodies, Protozoan
Cross Reactions
Epitopes, T-Lymphocyte
Escherichia coli
Malaria Vaccines
Malaria, Falciparum
Merozoite Surface Protein 1
Mice
Plasmodium falciparum
Rabbits
Recombinant Fusion Proteins

Chemicals

Antibodies, Protozoan
Epitopes, T-Lymphocyte
Malaria Vaccines
Merozoite Surface Protein 1
Recombinant Fusion Proteins

Word Cloud

Created with Highcharts 10.0.0proteinblock2hybridtypespolyvalentallelicfalciparumrecombinantexpressedfullsurface1MSP1PlasmodiumcandidatevaccinepolymorphicepitopesN-terminalmajorproteinsmicesub-componentmodulesantibodiesdiverseMerozoiteimplicatedimportanttargetacquiredimmunitycomponentsincluderegiondesignedincorporatingsequencesthreetogethercompositerepeatsequenceoneflankingTcellcomparedseriescontainingmodularsub-componentssimilarlyEscherichiacoliImmunogenicitytestedrabbitscomparativeimmunogenicitystudiesperformedinducedhightitreseparatewiderangenaturallypanelPisolatespartialantigeniccoverageexpectedencouragesdevelopmentevaluationblood-stagecomponentmalariaelicitsmerozoite

Similar Articles

Cited By