Human Antibodies that Slow Erythrocyte Invasion Potentiate Malaria-Neutralizing Antibodies.

Daniel G W Alanine; Doris Quinkert; Rasika Kumarasingha; Shahid Mehmood; Francesca R Donnellan; Nana K Minkah; Bernadeta Dadonaite; Ababacar Diouf; Francis Galaway; Sarah E Silk; Abhishek Jamwal; Jennifer M Marshall; Kazutoyo Miura; Lander Foquet; Sean C Elias; Geneviève M Labbé; Alexander D Douglas; Jing Jin; Ruth O Payne; Joseph J Illingworth; David J Pattinson; David Pulido; Barnabas G Williams; Willem A de Jongh; Gavin J Wright; Stefan H I Kappe; Carol V Robinson; Carole A Long; Brendan S Crabb; Paul R Gilson; Matthew K Higgins; Simon J Draper

doi:10.1016/j.cell.2019.05.025

Human Antibodies that Slow Erythrocyte Invasion Potentiate Malaria-Neutralizing Antibodies.

Daniel G W Alanine, Doris Quinkert, Rasika Kumarasingha, Shahid Mehmood, Francesca R Donnellan, Nana K Minkah, Bernadeta Dadonaite, Ababacar Diouf, Francis Galaway, Sarah E Silk, Abhishek Jamwal, Jennifer M Marshall, Kazutoyo Miura, Lander Foquet, Sean C Elias, Geneviève M Labbé, Alexander D Douglas, Jing Jin, Ruth O Payne, Joseph J IllingworthDavid J Pattinson, David Pulido, Barnabas G Williams, Willem A de Jongh, Gavin J Wright, Stefan H I Kappe, Carol V Robinson, Carole A Long, Brendan S Crabb, Paul R Gilson, Matthew K Higgins, Simon J Draper

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

Abstract

The Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) is the leading target for next-generation vaccines against the disease-causing blood-stage of malaria. However, little is known about how human antibodies confer functional immunity against this antigen. We isolated a panel of human monoclonal antibodies (mAbs) against PfRH5 from peripheral blood B cells from vaccinees in the first clinical trial of a PfRH5-based vaccine. We identified a subset of mAbs with neutralizing activity that bind to three distinct sites and another subset of mAbs that are non-functional, or even antagonistic to neutralizing antibodies. We also identify the epitope of a novel group of non-neutralizing antibodies that significantly reduce the speed of red blood cell invasion by the merozoite, thereby potentiating the effect of all neutralizing PfRH5 antibodies as well as synergizing with antibodies targeting other malaria invasion proteins. Our results provide a roadmap for structure-guided vaccine development to maximize antibody efficacy against blood-stage malaria. Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.

Original language	English
Pages (from-to)	216-228
Journal	Cell
Volume	178
Issue number	1
Early online date	27 Jun 2019
DOIs	https://doi.org/10.1016/j.cell.2019.05.025
Publication status	Published - 27 Jun 2019

Bibliographical note

Keywords

parasites and microbes
staffpaper

Access to Document

10.1016/j.cell.2019.05.025

PIIS0092867419305537
© 2019 The Author(s).
Final published version, 4.79 MBLicence: CC BY

https://linkinghub.elsevier.com/retrieve/pii/S0092867419305537

Cite this

Alanine, D. G. W., Quinkert, D., Kumarasingha, R., Mehmood, S., Donnellan, F. R., Minkah, N. K., Dadonaite, B., Diouf, A., Galaway, F., Silk, S. E., Jamwal, A., Marshall, J. M., Miura, K., Foquet, L., Elias, S. C., Labbé, G. M., Douglas, A. D., Jin, J., Payne, R. O., ... Draper, S. J. (2019). Human Antibodies that Slow Erythrocyte Invasion Potentiate Malaria-Neutralizing Antibodies. Cell, 178(1), 216-228. https://doi.org/10.1016/j.cell.2019.05.025

@article{93dcebc4b7ff4d228d3b8682bc4b1c7a,

title = "Human Antibodies that Slow Erythrocyte Invasion Potentiate Malaria-Neutralizing Antibodies.",

abstract = "The Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) is the leading target for next-generation vaccines against the disease-causing blood-stage of malaria. However, little is known about how human antibodies confer functional immunity against this antigen. We isolated a panel of human monoclonal antibodies (mAbs) against PfRH5 from peripheral blood B cells from vaccinees in the first clinical trial of a PfRH5-based vaccine. We identified a subset of mAbs with neutralizing activity that bind to three distinct sites and another subset of mAbs that are non-functional, or even antagonistic to neutralizing antibodies. We also identify the epitope of a novel group of non-neutralizing antibodies that significantly reduce the speed of red blood cell invasion by the merozoite, thereby potentiating the effect of all neutralizing PfRH5 antibodies as well as synergizing with antibodies targeting other malaria invasion proteins. Our results provide a roadmap for structure-guided vaccine development to maximize antibody efficacy against blood-stage malaria. Copyright {\textcopyright} 2019 The Author(s). Published by Elsevier Inc. All rights reserved.",

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author = "Alanine, {Daniel G W} and Doris Quinkert and Rasika Kumarasingha and Shahid Mehmood and Donnellan, {Francesca R} and Minkah, {Nana K} and Bernadeta Dadonaite and Ababacar Diouf and Francis Galaway and Silk, {Sarah E} and Abhishek Jamwal and Marshall, {Jennifer M} and Kazutoyo Miura and Lander Foquet and Elias, {Sean C} and Labb{\'e}, {Genevi{\`e}ve M} and Douglas, {Alexander D} and Jing Jin and Payne, {Ruth O} and Illingworth, {Joseph J} and Pattinson, {David J} and David Pulido and Williams, {Barnabas G} and {de Jongh}, {Willem A} and Wright, {Gavin J} and Kappe, {Stefan H I} and Robinson, {Carol V} and Long, {Carole A} and Crabb, {Brendan S} and Gilson, {Paul R} and Higgins, {Matthew K} and Draper, {Simon J}",

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doi = "10.1016/j.cell.2019.05.025",

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Alanine, DGW, Quinkert, D, Kumarasingha, R, Mehmood, S, Donnellan, FR, Minkah, NK, Dadonaite, B, Diouf, A, Galaway, F, Silk, SE, Jamwal, A, Marshall, JM, Miura, K, Foquet, L, Elias, SC, Labbé, GM, Douglas, AD, Jin, J, Payne, RO, Illingworth, JJ, Pattinson, DJ, Pulido, D, Williams, BG, de Jongh, WA, Wright, GJ, Kappe, SHI, Robinson, CV, Long, CA, Crabb, BS, Gilson, PR, Higgins, MK & Draper, SJ 2019, 'Human Antibodies that Slow Erythrocyte Invasion Potentiate Malaria-Neutralizing Antibodies.', Cell, vol. 178, no. 1, pp. 216-228. https://doi.org/10.1016/j.cell.2019.05.025

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AU - Alanine, Daniel G W

AU - Quinkert, Doris

AU - Kumarasingha, Rasika

AU - Mehmood, Shahid

AU - Donnellan, Francesca R

AU - Minkah, Nana K

AU - Dadonaite, Bernadeta

AU - Diouf, Ababacar

AU - Galaway, Francis

AU - Silk, Sarah E

AU - Jamwal, Abhishek

AU - Marshall, Jennifer M

AU - Miura, Kazutoyo

AU - Foquet, Lander

AU - Elias, Sean C

AU - Labbé, Geneviève M

AU - Douglas, Alexander D

AU - Jin, Jing

AU - Payne, Ruth O

AU - Illingworth, Joseph J

AU - Pattinson, David J

AU - Pulido, David

AU - Williams, Barnabas G

AU - de Jongh, Willem A

AU - Wright, Gavin J

AU - Kappe, Stefan H I

AU - Robinson, Carol V

AU - Long, Carole A

AU - Crabb, Brendan S

AU - Gilson, Paul R

AU - Higgins, Matthew K

AU - Draper, Simon J

PY - 2019/6/27

Y1 - 2019/6/27

N2 - The Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) is the leading target for next-generation vaccines against the disease-causing blood-stage of malaria. However, little is known about how human antibodies confer functional immunity against this antigen. We isolated a panel of human monoclonal antibodies (mAbs) against PfRH5 from peripheral blood B cells from vaccinees in the first clinical trial of a PfRH5-based vaccine. We identified a subset of mAbs with neutralizing activity that bind to three distinct sites and another subset of mAbs that are non-functional, or even antagonistic to neutralizing antibodies. We also identify the epitope of a novel group of non-neutralizing antibodies that significantly reduce the speed of red blood cell invasion by the merozoite, thereby potentiating the effect of all neutralizing PfRH5 antibodies as well as synergizing with antibodies targeting other malaria invasion proteins. Our results provide a roadmap for structure-guided vaccine development to maximize antibody efficacy against blood-stage malaria. Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.

AB - The Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) is the leading target for next-generation vaccines against the disease-causing blood-stage of malaria. However, little is known about how human antibodies confer functional immunity against this antigen. We isolated a panel of human monoclonal antibodies (mAbs) against PfRH5 from peripheral blood B cells from vaccinees in the first clinical trial of a PfRH5-based vaccine. We identified a subset of mAbs with neutralizing activity that bind to three distinct sites and another subset of mAbs that are non-functional, or even antagonistic to neutralizing antibodies. We also identify the epitope of a novel group of non-neutralizing antibodies that significantly reduce the speed of red blood cell invasion by the merozoite, thereby potentiating the effect of all neutralizing PfRH5 antibodies as well as synergizing with antibodies targeting other malaria invasion proteins. Our results provide a roadmap for structure-guided vaccine development to maximize antibody efficacy against blood-stage malaria. Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.

KW - parasites and microbes

KW - staffpaper

U2 - 10.1016/j.cell.2019.05.025

DO - 10.1016/j.cell.2019.05.025

M3 - Article

SN - 0092-8674

VL - 178

SP - 216

EP - 228

JO - Cell

JF - Cell

IS - 1

ER -