Recombinant protein vaccines against the asexual blood-stages of Plasmodium falciparum

It is now more than 25 years since asexual blood-stage antigens of Plasmodium falciparum were first expressed as recombinant proteins. Although many asexual blood-stage vaccine candidates have been identified, none has yet been fully evaluated in clinical trials. The results of studies in animal models, and from in vitro studies with P. falciparum, indicate that antibody responses induced by many of these recombinant proteins can inhibit parasite development, but so far the evidence that protection can be achieved in exposed human populations is limited. Recombinant forms of MSP2 and AMA1 expressed in E. coli have had significant effects in Phase II trials, although for both antigens the effect was against a subset of parasites expressing a form of these polymorphic antigens related to that in the vaccine. More knowledge of the antigenic structure of the native parasite antigens is required so that recombinant protein constructs can be optimized to induce the correct antibody fine specificity. The very different structural characteristics of MSP2 and AMA1 are discussed, as are some approaches being taken to overcoming the problem of diversity in these antigens.