Back to Search
Start Over
Analysis of the diverse antigenic landscape of the malaria protein RH5 identifies a potent vaccine-induced human public antibody clonotype.
- Source :
-
Cell [Cell] 2024 Sep 05; Vol. 187 (18), pp. 4964-4980.e21. Date of Electronic Publication: 2024 Jul 25. - Publication Year :
- 2024
-
Abstract
- The highly conserved and essential Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) has emerged as the leading target for vaccines against the disease-causing blood stage of malaria. However, the features of the human vaccine-induced antibody response that confer highly potent inhibition of malaria parasite invasion into red blood cells are not well defined. Here, we characterize 236 human IgG monoclonal antibodies, derived from 15 donors, induced by the most advanced PfRH5 vaccine. We define the antigenic landscape of this molecule and establish that epitope specificity, antibody association rate, and intra-PfRH5 antibody interactions are key determinants of functional anti-parasitic potency. In addition, we identify a germline IgG gene combination that results in an exceptionally potent class of antibody and demonstrate its prophylactic potential to protect against P. falciparum parasite challenge in vivo. This comprehensive dataset provides a framework to guide rational design of next-generation vaccines and prophylactic antibodies to protect against blood-stage malaria.<br />Competing Interests: Declaration of interests J.R.B., A.J.R.C., G.G., B.G.W., L.D.W.K., L.T.W., J.T., K. McHugh, and S.J.D. are inventors on patent applications relating to RH5 malaria vaccines and/or antibodies. A.M.M. and S.J.D. have consulted to GSK on malaria vaccines. A.M.M. has an immediate family member who is an inventor on patent applications relating to RH5 malaria vaccines and antibodies.<br /> (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Humans
Animals
Mice
Epitopes immunology
Erythrocytes parasitology
Erythrocytes immunology
Female
Carrier Proteins immunology
Malaria Vaccines immunology
Plasmodium falciparum immunology
Antibodies, Protozoan immunology
Malaria, Falciparum immunology
Malaria, Falciparum prevention & control
Malaria, Falciparum parasitology
Protozoan Proteins immunology
Antibodies, Monoclonal immunology
Immunoglobulin G immunology
Antigens, Protozoan immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4172
- Volume :
- 187
- Issue :
- 18
- Database :
- MEDLINE
- Journal :
- Cell
- Publication Type :
- Academic Journal
- Accession number :
- 39059380
- Full Text :
- https://doi.org/10.1016/j.cell.2024.06.015