Human Antibodies that Slow Erythrocyte Invasion Potentiate Malaria-Neutralizing Antibodies

被引：99

作者：

Alanine, Daniel G. W. ^{[1
,2
]}

Quinkert, Doris ^{[1
]}

Kumarasingha, Rasika ^{[3
]}

Mehmood, Shahid ^{[4
]}

Donnellan, Francesca R. ^{[1
]}

Minkah, Nana K. ^{[5
]}

Dadonaite, Bernadeta ^{[1
]}

Diouf, Ababacar ^{[6
]}

Galaway, Francis ^{[7
]}

Silk, Sarah E. ^{[1
]}

Jamwal, Abhishek ^{[2
]}

Marshall, Jennifer M. ^{[1
]}

Miura, Kazutoyo ^{[6
]}

Foquet, Lander ^{[5
]}

Elias, Sean C. ^{[1
]}

Labbe, Genevieve M. ^{[1
]}

Douglas, Alexander D. ^{[1
]}

Jin, Jing ^{[1
]}

Payne, Ruth O. ^{[1
]}

Illingworth, Joseph J. ^{[1
]}

Pattinson, David J. ^{[1
]}

Pulido, David ^{[1
]}

Williams, Barnabas G. ^{[1
]}

de Jongh, Willem A. ^{[8
]}

Wright, Gavin J. ^{[7
]}

Kappe, Stefan H., I ^{[5
]}

Robinson, Carol, V ^{[4
]}

Long, Carole A. ^{[6
]}

Crabb, Brendan S. ^{[3
]}

Gilson, Paul R. ^{[3
]}

Higgins, Matthew K. ^{[2
]}

Draper, Simon J. ^{[1
]}

机构：

[1] Univ Oxford, Jenner Inst, Old Rd Campus Res Bldg, Oxford OX3 7DQ, England

[2] Univ Oxford, Dept Biochem, South Parks Rd, Oxford OX1 3QU, England

[3] Burnet Inst, 85 Commercial Rd, Melbourne, Vic 3004, Australia

[4] Univ Oxford, Dept Chem, Oxford OX1 3QZ, England

[5] Seattle Childrens Res Inst, Ctr Global Infect Dis Res, 307 Westlake Ave N,500, Seattle, WA 98109 USA

[6] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA

[7] Wellcome Trust Sanger Inst, Cell Surface Signalling Lab, Cambridge CB10 1SA, England

[8] ExpreS2 Biotechnol, SCION DTU Sci Pk,Agern Alle 1, DK-2970 Horsholm, Denmark

来源：

CELL | 2019年 / 178卷 / 01期

基金：

英国医学研究理事会; 澳大利亚国家健康与医学研究理事会; 英国惠康基金;

关键词：

PLASMODIUM-FALCIPARUM INVASION; MONOCLONAL-ANTIBODIES; INHIBITORY ANTIBODIES; PROTEIN; VACCINE; BINDING; INFECTION; PROTECTION; COMPLEX; EPITOPE;

D O I：

10.1016/j.cell.2019.05.025

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 n proteins. Our results provide a roadmap for structure-guided vaccine development to maximize antibody efficacy against blood-stage malaria.

引用

页码：216 / +

页数：34

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