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Rhop-3 protein conservation among Plasmodium species and induced protection against lethal P. yoelii and P. berghei challenge

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Abstract

In the present study, Rhop-3 polymorphism among Plasmodium falciparum field and laboratory isolates and among rodent Plasmodium species was investigated and identified. The Rhop-3 gene was found in all Plasmodium species so far tested. The overall structure of the Rhop-3 protein was found conserved among P. falciparum, Plasmodium yoelii, and Plasmodium berghei. However, it was more conserved among rodent Plasmodium species than between P. falciparum and Plasmodium vivax. The most conserved regions of Rhop-3 are the second half of exon 6 (amino acid #548 to #665) and the beginning of exon 3 (amino acid #59 to #210). Recombinant C-terminal partial and full-length Rhop-3 proteins of P. yoelii and P. berghei were expressed in Escherichia coli and purified. Immunization-challenge experiments in mice using recombinant Rhop-3 proteins led to a delay in parasite development and protected mice from a homologous lethal challenge infection. In a group of eight outbred Carworth Farm White (CFW) mice immunized with P. yoelii C-terminal recombinant His-Y1412 protein, three mice (37.5%) were protected from a lethal P. yoelii challenge. In BALB/cJ mice one mouse (20%) survived the infection. Immunization of mice with P. berghei recombinant full-length Rhop-3 protein in BALB/cJ mice led to a 40% survival from lethal P. berghei challenge. CFW mice immunized with P. berghei recombinant full-length Rhop-3 protein showed a significant delay in parasite development with a heterologous P. yoelii challenge. The Rhop-3 protein is a promising candidate for an asexual stage malaria vaccine.

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Acknowledgements

This study was supported by funds from NIH grant AI36470, Cleveland State University Established Full-time Faculty Research Development (EFFRD) grant program, and AY03 Doctoral Dissertation Research Expense Award (from the University Research Council, Cleveland State University). TSY is grateful to the New England Biolabs Molecular Biology Summer Workshops 2000 and we thank MR4/ATCC for P. berghei cDNA clones.

Author information

Correspondence to Tobili Y. Sam-Yellowe.

Additional information

Nucleotide sequence data reported in this paper have been submitted to GeneBank with the Accession numbers: AY044907-AY044914.

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Wang, T., Fujioka, H., Drazba, J.A. et al. Rhop-3 protein conservation among Plasmodium species and induced protection against lethal P. yoelii and P. berghei challenge. Parasitol Res 99, 238–252 (2006). https://doi.org/10.1007/s00436-006-0136-9

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Keywords

  • Plasmodium
  • Plasmodium Species
  • Infected Erythrocyte
  • Plasmodium Berghei
  • Asexual Stage