Disrupting CD147-RAP2 interaction abrogates erythrocyte invasion by Plasmodium falciparum

08 Mar 2018
Zhang MY, Zhang Y, Wu XD, Zhang K, Lin P, Bian HJ, Qin MM, Huang W, Wei D, Zhang Z, Wu J, Chen R, Feng F, Wang B, Nan G, Zhu P, Chen ZN

 

Effective vaccines against malaria caused by are still lacking, and the molecular mechanism of the host-parasite interaction is not fully understood. Here we demonstrate that the interaction of RAP2, a parasite-secreted rhoptry protein that functions in the parasitophorous vacuole formation stage of the invasion, and CD147 on the host erythrocyte is essential for erythrocyte invasion by and is independent from all previously identified interactions involved. Importantly, the blockade of the CD147-RAP2 interaction by HP6H8, a humanized CD147 antibody, completely abolished the parasite invasion with both cure and preventative functions in a humanized mouse model. Together with its long half-life on human red blood cells and its safety profile in cynomolgus monkeys, HP6H8 is the first antibody that offers an advantageous approach by targeting a more conserved late-stage parasite ligand for preventing as well as treating severe malaria.