Rhop-3 protein conservation among Plasmodium species and induced protection against lethal P. yoelii and P. berghei challenge.
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.
Department of Biological, Geological and Environmental Sciences, Cleveland State University, Cleveland, OH, USA. wangtmtj@yahoo.com
Tongmin
T
Wang
Hisashi
H
Fujioka
Judith A
JA
Drazba
Tobili Y
TY
Sam-Yellowe
D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D016054:DNA, Protozoan / Q000737:chemistry / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics; D007114:Immunization; D008288:Malaria / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D018512:Parasitemia; D010961:Plasmodium / Q000235:genetics*; D010962:Plasmodium berghei / Q000235:genetics / Q000276:immunology*; D010967:Plasmodium yoelii / Q000235:genetics / Q000276:immunology*; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000235:genetics* / Q000276:immunology*; D011994:Recombinant Proteins / Q000235:genetics / Q000302:isolation & purification; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid
D016054:DNA, Protozoan; D015800:Protozoan Proteins; D011994:Recombinant Proteins; C065352:rhoptry associated protein, Plasmodium