Identification and characterization of the protective hepatocyte erythrocyte protein 17 kDa gene of Plasmodium yoelii, homolog of Plasmodium falciparum exported protein 1.
We recently reported the discovery of a 17-kDa Plasmodium yoelii protein expressed in infected hepatocytes and erythrocytes, P. yoelii hepatocyte erythrocyte protein 17 (PyHEP17), and have demonstrated that this protein is a target of protective antibodies and T cells. Here, we report the identification and characterization of the gene encoding this protein and reveal that it is composed of two exons. Immunization of mice with PyHEP17 plasmid DNA induces antibodies, cytotoxic T lymphocytes, and protective immunity directed against the infected hepatocyte. Based on extensive sequence homology, expression pattern, and antigenic cross-reactivity, the Plasmodium falciparum homolog of PyHEP17 is identified as the protein known as exported protein-1 (PfExp-1), also called antigen 5.1, circumsporozoite related antigen, or QF116. Identity between PyHEP17 and PfExp-1 is 37% at the amino acid level (60/161 residues), mapping primarily to two regions within the second exon of 73% (16/22 residues) and 71% (25/35 residues) identity. On this basis, PfExp-1 is proposed as an important component of pre-erythrocytic human malaria vaccines.
Doolan
D L
DL
Malaria Program, Naval Medical Research Institute, Bethesda, Maryland 20889-5607, USA.
Hedstrom
R C
RC
Rogers
W O
WO
Charoenvit
Y
Y
Rogers
M
M
de la Vega
P
P
Hoffman
S L
SL
D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan / Q000235:genetics; D001483:Base Sequence; D003429:Cross Reactions; D004912:Erythrocytes / Q000469:parasitology; D017125:Genes, Protozoan; D008099:Liver / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010967:Plasmodium yoelii / Q000235:genetics*; D015800:Protozoan Proteins / Q000235:genetics* / Q000276:immunology; D017386:Sequence Homology, Amino Acid
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; C100626:HEP17 protein, Plasmodium falciparum; D015800:Protozoan Proteins; C063362:QF116 antigen, Plasmodium falciparum