A rhoptry antigen ofPlasmodium falciparumis protective inSaimirimonkeys

Abstract

SUMMARYA non-polymorphic antigen associated with the rhoptry organelles of Plasmodium falciparum has been purified by immunoaffinity chromatography. The antigen, RAP-1 (rhoptry associated protein-1), which is defined by monoclonal antibodies which inhibit parasite growth in vitro, is a multi-component antigen consisting of four major proteins of 80, 65, 42 and 40 kDa and two minor proteins of 77 and 70 kDa. These proteins were electro-eluted from preparative sodium dodecyl sulphate polyacrylamide gels and protected Saimiri sciureus monkeys from a lethal blood-stage infection of P. falciparum malaria. Sera from the protected animals recognized only proteins of the RAP-1 antigen when used to probe a Western blot of total parasite protein extract, confirming that RAP-1 is responsible for eliciting the protective immune response.

Adhesion of normal and Plasmodium falciparum ring–infected erythrocytes to endothelial cells and the placenta involves the rhoptry-derived ring surface protein-2

“…The RSP-2 protein complex recognized by the mAbs B4, C10, and D10 had features similar to the previously described rhoptry complex composed of RAP-1, RAP-2, and RAP-3. 15,16 The mAbs recognize a recombinant RAP-2 GST fusion protein, indicating that RSP-2 is encoded by the RAP-2 gene. Analysis of mutant RAP-1 parasites confirmed the identity of RSP-2 and RAP-2 (Sterkers et al, manuscript in preparation).…”

“…The fact that mAbs B4 and C10 recognize a 42-kDa molecule of a rhoptry protein complex suggested that RSP-2 could correspond to a protein identified earlier as rhoptry associated protein 2Ј (RAP2). 15,16 To address this question, we expressed RAP2 as glutathione-S-transferase (GST) fusion protein in Escherichia coli. mAbs B4 and C10 recognize the 71-kDa RAP-2 fusion protein by Western blot ( Figure 2D).…”

Efficacy of vaccines containing rhoptry-associated proteins RAP1 and RAP2 of Plasmodium falciparum in Saimiri boliviensis monkeys.

“…To allow a direct comparison with the previously obtained protection data of RAP1 and RAP2 in monkeys, 9 in this study we used S. boliviensis and the FUP strain of P. falciparum. Previously, we had established the reproducibility of Aotus nancymai monkeys and the Vietnam Oak Knoll strain of P. falciparum as a preferred model based on the reproducibility of this combination.…”

“…[2][3][4][5][6][7] Two vaccine trials in Saimiri sciureus monkeys with RAP1 and RAP2 extracted from parasites using Freund's adjuvants demonstrated that these proteins may induce protective immunity. [8][9][10][11] Monkeys immunized with Plasmodium falciparum parasite-derived RAP1 and RAP2 (PfRAP1 and PfRAP2), isolated by affinity chromatography and further purified by SDS (sodium dodecyl sulfate) polyacrylamide electrophoresis, had substantially lower peak parasitemia when compared to control monkeys and did not require drug treatment.…”

Associations between Responses to the Rhoptry-Associated Membrane Antigen of Plasmodium falciparum and Immunity to Malaria Infection

“…In vitro growth inhibition assays have indicated that antibodies directed against the RAP1 and RAP2 proteins have inhibitory effects on P. falciparum growth in in vitro culture (6,9,14,18). Moreover, immunization of Saimiri monkeys with RAP1 protected the animals from a lethal malaria parasite infection (17), suggesting that interference with the rhoptry protein function by immune responses can prevent RBC invasion.…”