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Disrupting CD147-RAP2 interaction abrogates erythrocyte invasion by Plasmodium falciparum.

Disrupting CD147-RAP2 interaction abrogates erythrocyte invasion by Plasmodium falciparum.

Authors :
Min-Min Qin
Ping Zhu
Meng-Yao Zhang
Yang Zhang
Xiao-Dong Wu
Peng Lin
Hui-Jie Bian
Wan Huang
Ding Wei
Zhao Zhang
Jiao Wu
Ruo Chen
Fei Feng
Bin Wang
Gang Nan
Zhi-Nan Chen
Kun Zhang
Source :
Blood. 3/8/2018, Vol. 131 Issue 10, p1111-1121. 11p.
Publication Year :
2018

Abstract

Effective vaccines against malaria caused by Plasmodium falciparum 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 P 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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00064971
Volume :
131
Issue :
10
Database :
Academic Search Index
Journal :
Blood
Publication Type :
Academic Journal
Accession number :
128368009
Full Text :
https://doi.org/10.1182/blood-2017-08-802918