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Disrupting CD147-RAP2 interaction abrogates erythrocyte invasion by Plasmodium falciparum

Meng-Yao Zhang, Yang Zhang, Xiao-Dong Wu, Kun Zhang, Peng Lin, Hui-Jie Bian, Min-Min Qin, Wan Huang, Ding Wei, Zhao Zhang, Jiao Wu, Ruo Chen, Fei Feng, Bin Wang, Gang Nan, Ping Zhu and Zhi-Nan Chen

Key points

  • The CD147-RAP2 interaction is essential for erythrocyte invasion by P. falciparum and is independent from the known interactions involved.

  • HP6H8, specifically interrupts the CD147-RAP2 pair, is capable of complete elimination and prevention of Pf infection in humanized mice.

Abstract

Effective vaccines against Plasmodium falciparum malaria 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 functioning in the parasitophorous vacuole formation stage of the invasion, and CD147 on host erythrocyte is essential for erythrocyte invasion by Plasmodium falciparum 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.

  • Submitted August 22, 2017.
  • Accepted January 8, 2018.