Alanine, D.G.W., Quinkert, D., Kumarasingha, R. et al. (29 more authors) (2019) Human antibodies that slow erythrocyte invasion potentiate malaria-neutralizing antibodies. Cell, 178 (1). e21. pp. 216-228. ISSN 0092-8674
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 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/). |
Keywords: | RH5; X-ray crystallography; blood-stage; live-cell microscopy; malaria; merozoite; monoclonal antibody; neutralization; structural vaccinology; synergy |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Infection and Immunity (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 09 Jul 2019 09:29 |
Last Modified: | 09 Jul 2019 09:29 |
Status: | Published |
Publisher: | Elsevier (Cell Press) |
Refereed: | Yes |
Identification Number: | 10.1016/j.cell.2019.05.025 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:147850 |