Open AccessNeutralising antibodies block the function of Rh5/Ripr/CyRPA complex during invasion of Plasmodium falciparum into human erythrocytes
Author(s) -
Healer Julie,
Wong Wilson,
Thompson Jennifer K.,
He Wengqiang,
Birkinshaw Richard W.,
Miura Kazutoyo,
Long Carol A.,
Soroka Vladislav,
Søgaard Teit Max Moscote,
Jørgensen Thomas,
Jongh Willem A.,
Weir Christopher,
Svahn Ella,
Czabotar Peter E.,
Tham WaiHong,
Mueller Ivo,
Barlow Paul N.,
Cowman Alan F.
Publication year - 2019
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/cmi.13030
Subject(s) - plasmodium falciparum , biology , basigin , antibody , epitope , malaria , virology , immunology , biochemistry , matrix metalloproteinase
An effective vaccine is a priority for malaria control and elimination. The leading candidate in the Plasmodium falciparum blood stage is PfRh5. PfRh5 assembles into trimeric complex with PfRipr and PfCyRPA in the parasite, and this complex is essential for erythrocyte invasion. In this study, we show that antibodies specific for PfRh5 and PfCyRPA prevent trimeric complex formation. We identify the EGF‐7 domain on PfRipr as a neutralising epitope and demonstrate that antibodies against this region act downstream of complex formation to prevent merozoite invasion. Antibodies against the C‐terminal region of PfRipr were more inhibitory than those against either PfRh5 or PfCyRPA alone, and a combination of antibodies against PfCyRPA and PfRipr acted synergistically to reduce invasion. This study supports prioritisation of PfRipr for development as part of a next‐generation antimalarial vaccine.