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Human Antibodies that Slow Erythrocyte Invasion Potentiate Malaria-Neutralizing Antibodies
- Source :
- 'Cell ', vol: 178, pages: 216-228 (2019)
-
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.
- Subjects :
- Adult
Male
Erythrocytes
Adolescent
Plasmodium falciparum
Protozoan Proteins
Antibodies, Protozoan
Cross Reactions
Rats, Sprague-Dawley
Epitopes
Young Adult
Malaria Vaccines
Animals
Humans
Malaria, Falciparum
Binding Sites
Merozoites
Antibodies, Monoclonal
Middle Aged
Antibodies, Neutralizing
Healthy Volunteers
Rats
HEK293 Cells
Female
Rabbits
Carrier Proteins
Subjects
Details
- Language :
- English
- ISSN :
- 00928674 and 10974172
- Volume :
- 178
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Cell
- Accession number :
- edsair.pmid.dedup....41d14c06215591dbc2c3bbf32bec2bbd
- Full Text :
- https://doi.org/10.1016/j.cell.2019.05.025