biorxiv.org
Dynamic hinge-motion of PfRIPR revealed by malaria invasion inhibitory antibodies
The PfPCRCR complex is essential for invasion of human erythrocytes by the deadliest malaria parasite, Plasmodium falciparum . Antibodies against each subunit of PfPCRCR prevent erythrocyte invasion and the PfRH5 component is currently the most advanced blood-stage malaria vaccine. Central within PfPCRCR is PfRIPR. This complex molecule contains a core and a flexible tail and allows PfPCRCR to bridge the parasite and erythrocyte during invasion. In this study, we generated a small panel of human monoclonal antibodies against PfRIPR. We structurally characterised four PfRIPR tail-binding antibodies in complex with PfRIPR fragments. We show that growth-inhibitory antibody RP.012 induces a kink in the PfRIPR tail while non-inhibitory antibodies do not. Furthermore, we show that these four antibodies modulate each other, either through antagonism or by acting synergistically. These studies have implications for the design of PfRIPR-based vaccine immunogens and indicate that the tail of PfRIPR undergoes essential conformational changes during erythrocyte invasion. ### Competing Interest Statement J.T., A.C., and L.T.W. are coinventors on a provisional patent filed on the human mAbs described in this study (63/777,850). The other authors have no competing interests. Wellcome Trust, https://ror.org/029chgv08, 220797/Z/20/Z Medical Research Council, MR/Z505687/1 Gates Foundation, INV-078815
