Plasmodium yoelii: 17-kDa Hepatic and Erythrocytic Stage Protein Is the Target of an Inhibitory Monoclonal Antibody

Identification and Characterization of the Protective Gene of homolog of Exported Protein 1

“…PfExp-1 is a 23-kDa liver-stage (20) and blood-stage antigen secreted by the parasite into the host cell, accumulating at the parasitophorous vacuole membrane and within vesicles in the infected red cell cytoplasm. This pattern of intracellular localization is identical to that of PyHEP17 (1). PfExp-1 is characterized by intragenic non-coding regions and consists of three exons with a total size of 161 amino acids (486 bp).…”

“…The antigen recognized by this mAb has been designated PyHEP17 (1). The gt11 clone with the longest insert was selected for further characterization.…”

“…Neither PyHEP17 nor PfExp-1 are present in sporozoites, but both antigens are first expressed during the liver-stage of the parasite's life cycle, are present throughout the erythrocytic stage, and are exported into the cytoplasm of infected hepatocytes and erythrocytes (1,3,20); (iii) Western blot analysis of P. yoelii infected hepatocytes 3 and erythrocytes (1) using NYLS3 mAb identifies a protein of similar size to that identified in infected P. falciparum red blood cells; and (iv) consistent with the degree of sequence identity between PyHEP17 and PfExp-1, there is antigenic cross-reactivity. A mAb specific for PfExp-1, mAbN1 (17), PfExp-1 polyclonal sera, and human sera from individuals resident in an endemic area recognize COS cells transfected with PyHEP17Ex1.2 plasmid DNA and react with P. yoelii-infected liver-stage and blood-stage parasites (data not presented).…”

“…antibody (mAb) 1 Navy yoelii liver stage 3 (NYLS3) which specifically eliminates liver-stage parasites from in vitro culture and delays the onset and reduces the density of blood-stage parasitemia in vivo (1). A DNA vaccine containing the cDNA encoding 67.5% of PyHEP17 (complete exon 1 and 57% of exon 2) protects three of five inbred strains of mice differing in H-2 haplotype and genetic backgrounds, as well as 40 -50% of outbred mice, against P. yoelii sporozoite but not blood-stage challenge (2).…”

Monoclonal auto-antibodies and sera of autoimmune patients react with Plasmodium falciparum and inhibit its in vitro growth

“…Immunofluorescence antibody test (IFA�) reactivity of autoimmune disease patients' sera containing defined auto-antibodies against different asexual erythrocytic forms of Plasmodium falciparum NF54, �23 and �99.6 strains and Plasmodium yoelii 17XNL bodies (MoAb) were also used: (i) MoAb 2A10 (IgG2a), a stage and species-specific antibody directed to the P. falciparum circumsporozoite protein, which is expressed on the surface of sporozoites but not during the asexual erythrocytic stages (Wirtz et al 1987), (ii) MoAb Navy yoelii liver stage 3 (NYLS3, IgG1) directed against the 17 kDa liver stage antigen 3 protein of P. yoelii, which is expressed by liver stage parasites within 6 h of sporozoite invasion of mouse hepatocytes, throughout the asexual erythrocytic stages and on merozoites [NYLS3 is species-specific, does not cross-react with blood stage antigens and, as expected, does not inhibit P. falciparum growth (Charoenvit et al 1995)], (iii) MoAb 1C3 (IgG1, kappa) specific to the thrombospondin-related adhesive protein, which is expressed on both sporozoites and erythrocytic stages of P. falciparum (Robson et al 1995). It has been previously shown that 1C3 does not inhibit P. falciparum growth (Robson et al 1995).…”