Human antibodies that slow erythrocyte invasion potentiate malaria-neutralizing antibodies

Alanine, Daniel, Quinkert, Doris, Kumarasingha, Rasika, Mehmood, Shahid, Donnellan, Francesca R., Minkah, Nana K., Dadonaite, Bernadeta, Diouf, Ababacar, Galaway, Francis, Silk, Sarah E., Abhishek, Jamwal, Marshall, Jennifer M., Miura, Kazutoyo, Foquet, Lander, Elias, Sean C., Labbe, Genevieve M., Douglas, Alexander D., Jin, Jing, Payne, Ruth O., Illingworth, Joseph J., Pattinson, David, Pulido, David, Williams, Barnabas G., de Jongh, Willem A., Wright, Gavin J., Kappe, Stefan H.I., Robinson, Carol V., Long, Carole A., Crabb, Brendan S., Gilson, Paul R., Higgins, Matthew K., and Draper, Simon J. (2019) Human antibodies that slow erythrocyte invasion potentiate malaria-neutralizing antibodies. Cell, 178 (1). pp. 216-228.

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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.

Item ID: 60509
Item Type: Article (Research - C1)
ISSN: 1097-4172
Copyright Information: Copyright 2019 The Author(s). Published by Elsevier Inc.This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
Funders: European Union (EU), Wellcome Trust, Eurpoean Union (EU)
Projects and Grants: EU FP7/2007-201 MultiMalVax (305282), EU OptiMalVax (73327)
Date Deposited: 02 Dec 2019 00:21
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110705 Humoural Immunology and Immunochemistry @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 100%
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