Human Antibodies that Slow Erythrocyte Invasion Potentiate Malaria-Neutralizing Antibodies.
Adolescent
Adult
Animals
Antibodies, Monoclonal
/ immunology
Antibodies, Neutralizing
/ immunology
Antibodies, Protozoan
/ immunology
Binding Sites
Carrier Proteins
/ immunology
Cross Reactions
/ immunology
Epitopes
/ immunology
Erythrocytes
/ parasitology
Female
HEK293 Cells
Healthy Volunteers
Humans
Malaria Vaccines
/ immunology
Malaria, Falciparum
/ immunology
Male
Merozoites
/ physiology
Middle Aged
Plasmodium falciparum
/ immunology
Protozoan Proteins
/ immunology
Rabbits
Rats
Rats, Sprague-Dawley
Young Adult
RH5
X-ray crystallography
blood-stage
live-cell microscopy
malaria
merozoite
monoclonal antibody
neutralization
structural vaccinology
synergy
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
27 06 2019
27 06 2019
Historique:
received:
25
06
2018
revised:
05
03
2019
accepted:
13
05
2019
pubmed:
18
6
2019
medline:
9
4
2020
entrez:
18
6
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31204103
pii: S0092-8674(19)30553-7
doi: 10.1016/j.cell.2019.05.025
pmc: PMC6602525
pii:
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antibodies, Neutralizing
0
Antibodies, Protozoan
0
Carrier Proteins
0
Epitopes
0
Malaria Vaccines
0
Protozoan Proteins
0
RH5 protein, Plasmodium falciparum
0
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
216-228.e21Subventions
Organisme : Medical Research Council
ID : MR/N020413/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 206194
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 201477/Z/16/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N013468/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 104923/Z/14/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 106917/Z/15/Z
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/K025554/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 101020/Z/13/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 105399/Z/14/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/K017632/1
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.
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