A series of synthetic blood-stage malaria vaccine immunogens presenting the epitopes for growth-inhibitory antibodies from PfRH5

Abstract

The present invention relates to a series of polypeptides derived from Plasmodium falciparum Reticulocyte-binding protein Homologue 5 (PfRH5). Through an iterative design process starting with wild-type PfRH5, the inventors have produced a series of antigens comprising the 'top' portion of PfRH5 which is shown to express to high levels in E. coli, fold into a native-like structure and exhibit desired biophysical properties. In one embodiment, a PfRH5 variant is fused to an I53-50 nanoparticle to facilitate multivalent antigen presentation. Further, the embodiment RH5top is shown to elicit a significantly enhanced antibody response in rats compared to full length PfRH5. Claims to the 'top portion' polypeptides are disclosed, as well as claims to vaccines or immunogenic compositions comprising the polypeptides or corresponding nucleotides thereof, and medical use claims to the vaccines for use in inducing immune responses. [Figure 1]