1948 Immunodominant Region of Circumsporozoite Proteins

Protective immuni ty against several species of malar ia parasites has been obtained by vaccinat ion with x-irradiated sporozoites (reviewed in reference 1). The serum of protected animals reacts with the surface membrane of sporozoites and neutralizes their infectivity, which suggests that the effect of the vaccine is at least in part an t ibody mediated. T he membrane-associated protective antigens o f sporozoites of rodent (2, 3), simian (4), and h u m a n (5) malar ia have recently been identified by means o f monoclonal antibodies (mAb). 1 They are stage-specific proteins that are distributed uniformly over the entire surface of the parasite and are shed when crosslinked by antibodies (3). Evidence that these circumsporozoite (CS) proteins of different malar ia species are structurally, antigenically, and functionally related molecules has been presented elsewhere (6). O f par t icular interest were the observations that Fab fragments o f a m Ab against the CS protein of Plasmodium berghei inhibited the a t tachment and interiorization of these sporozoites into target ceils (7). These findings raised the intr iguing possibility that some of the epitopes recognized by the mAb might either coincide with or be in close proximity to the areas of the CS molecules that are involved in parasite penetration. To investigate this phenomenon further we compare here the specificities of a series of m A b against CS proteins of parasites of monkey (P. knowlesi) and h u m a n (P. vivax and P. falciparum) malaria, including some that neutralized the infectivity o f the sporozoites in vivo (4, 5) or in vitro. 2 We present evidence that in every instance the m A b recognize the same unique region of the CS molecule, which contains at least two identical epitopes.