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

doi:10.1111/cmi.13030

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

34 Citations (Scopus)

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 language	English
Article number	e13030
Number of pages	15
Journal	Cellular Microbiology
Volume	21
Issue number	7
DOIs	https://doi.org/10.1111/cmi.13030
Publication status	Published - 2019
Externally published	Yes

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Healer, J., Wong, W., Thompson, J. K., He, W., Birkinshaw, R. W., Miura, K., Long, C. A., Soroka, V., Søgaard, T. M. M., Jørgensen, T., de Jongh, W. A., Weir, C., Svahn, E., Czabotar, P. E., Tham, W. H., Mueller, I., Barlow, P. N., & Cowman, A. F. (2019). Neutralising antibodies block the function of Rh5/Ripr/CyRPA complex during invasion of Plasmodium falciparum into human erythrocytes. Cellular Microbiology, 21(7), Article e13030. https://doi.org/10.1111/cmi.13030

@article{ea7fd1484a0c4471bd4f7643a99da45b,

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

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.",

author = "Julie Healer and Wilson Wong and Thompson, {Jennifer K.} and Wengqiang He and Birkinshaw, {Richard W.} and Kazutoyo Miura and Long, {Carol A.} and Vladislav Soroka and S{\o}gaard, {Teit Max Moscote} and Thomas J{\o}rgensen and {de Jongh}, {Willem A.} and Christopher Weir and Ella Svahn and Czabotar, {Peter E.} and Tham, {Wai Hong} and Ivo Mueller and Barlow, {Paul N.} and Cowman, {Alan F.}",

note = "Publisher Copyright: {\textcopyright} 2019 The Authors Cellular Microbiology Published by John Wiley & Sons Ltd",

year = "2019",

doi = "10.1111/cmi.13030",

language = "English",

volume = "21",

journal = "Cellular Microbiology",

issn = "1462-5814",

publisher = "Wiley-Blackwell Publishing Ltd",

number = "7",

}

Healer, J, Wong, W, Thompson, JK, He, W, Birkinshaw, RW, Miura, K, Long, CA, Soroka, V, Søgaard, TMM, Jørgensen, T, de Jongh, WA, Weir, C, Svahn, E, Czabotar, PE, Tham, WH, Mueller, I, Barlow, PN & Cowman, AF 2019, 'Neutralising antibodies block the function of Rh5/Ripr/CyRPA complex during invasion of Plasmodium falciparum into human erythrocytes', Cellular Microbiology, vol. 21, no. 7, e13030. https://doi.org/10.1111/cmi.13030

TY - JOUR

T1 - Neutralising antibodies block the function of Rh5/Ripr/CyRPA complex during invasion of Plasmodium falciparum into human erythrocytes

AU - Healer, Julie

AU - Wong, Wilson

AU - Thompson, Jennifer K.

AU - He, Wengqiang

AU - Birkinshaw, Richard W.

AU - Miura, Kazutoyo

AU - Long, Carol A.

AU - Soroka, Vladislav

AU - Søgaard, Teit Max Moscote

AU - Jørgensen, Thomas

AU - de Jongh, Willem A.

AU - Weir, Christopher

AU - Svahn, Ella

AU - Czabotar, Peter E.

AU - Tham, Wai Hong

AU - Mueller, Ivo

AU - Barlow, Paul N.

AU - Cowman, Alan F.

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

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U2 - 10.1111/cmi.13030

DO - 10.1111/cmi.13030

M3 - Article

C2 - 30965383

AN - SCOPUS:85065038497

SN - 1462-5814

VL - 21

JO - Cellular Microbiology

JF - Cellular Microbiology

IS - 7

M1 - e13030

ER -

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

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