Neutralising antibodies block the function of Rh5/Ripr/CyRPA complex during invasion of Plasmodium falciparum into human erythrocytes

Julie Healer, Wilson Wong, Jennifer K Thompson, Wengqiang He, Richard W Birkinshaw, Kazutoyo Miura, Carol A Long, Vladislav Soroka, Teit Max Moscote Søgaard, Thomas Jørgensen, Willem A de Jongh, Christopher Weir, Ella Svahn, Peter E Czabotar, Wai-Hong Tham, Ivo Mueller, Paul N Barlow, Alan F Cowman

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)e13030
Number of pages15
JournalCellular Microbiology
Early online date9 Apr 2019
DOIs
Publication statusE-pub ahead of print - 9 Apr 2019

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