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Analysis of the Diverse Antigenic Landscape of the Malaria Invasion Protein RH5 Identifies a Potent Vaccine-Induced Human Public Antibody Clonotype
Open accessPreprint — published as 10.1016/j.cell.2024.06.015
Abstract
SUMMARY: The highly conserved and essential Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) has emerged as the leading target for vaccines that seek to protect 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 over 200 human IgG monoclonal antibodies induced by the most advanced PfRH5 vaccine. We define the antigenic landscape of this molecule, and establish epitope specificity, antibody association rate and intra-PfRH5 antibody interactions are key determinants of functional anti-parasitic potency. In addition, we identify a germline 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.
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Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764
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Metadata
- Authors
- Barrett, J. R., Pipini, D., Wright, N. D., Cooper, A. J. R., Gorini, G., Quinkert, D., Lias, A. M., Davies, H., Rigby, C., Aleshnick, M., Williams, B. G., Bradshaw, W. J., Paterson, N. G., Martinson, T., Kirtley, P., Picard, L., Wiggins, C. D., Donnellan, F. R., King, L. D. W., Wang, L. T., Popplewell, J. F., Silk, S. E., Swain, J. D. R., Skinner, K., Kotraiah, V., Noe, A. R., MacGill, R. S., King, C. R., Birkett, A. J., Soisson, L. A., Minassian, A. M., Lauffenburger, D. A., Miura, K., Long, C. A., Wilder, B. K., Koekemoer, L., Tan, J., Nielsen, C. M., McHugh, K., & Draper, S. J.
- Affiliations
- University of Oxford (GB)
- National Institutes of Health (US)
- Vaccine and Gene Therapy Institute (US)
- Diamond Light Source (GB)
- Massachusetts Institute of Technology (US)
- Carterra (United States) (US)
- Leidos (United States) (US)
- Program for Appropriate Technology in Health (US)
- United States Agency for International Development (US)
- National Institute of Allergy and Infectious Diseases (US)
- Corresponding author
- Draper, Simon J.
- ORCID
- Barrett, Jordan R.
- Pipini, Dimitra
- Wright, Nathan D.
- Cooper, Andrew J. R.
- Gorini, Giacomo
- Quinkert, Doris
- Lias, Amelia M.
- Davies, Hannah
- Rigby, Cassandra
- Aleshnick, Maya
- Williams, Barnabas G.
- Bradshaw, William J.
- Paterson, Neil G.
- Wiggins, Christine D.
- Donnellan, Francesca R.
- Wang, Lawrence T.
- Silk, Sarah E.
- Noe, Amy R.
- MacGill, Randall S.
- King, C. Richter
- Birkett, Ashley J.
- Minassian, Angela M.
- Lauffenburger, Douglas A.
- Miura, Kazutoyo
- Long, Carole A.
- Wilder, Brandon K.
- Koekemoer, Lizbé
- Tan, Joshua
- Nielsen, Carolyn M.
- McHugh, Kirsty
- Draper, Simon J.
- Venue
- Cell
- Publisher
- openRxiv
- Published
- 2023-10-04
- Volume
- 187
- Issue
- 18
- Pages
- 4964-4980.e21
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC11380582
- OpenAlex
- W4400978373
- Cited by
- 31
- References
- 1
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 12
- FWCI
- 12.84
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Cell (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (publishedVersion)
- Funders
- United States Agency for International Development (AID-OAA-C-15-00071, 7200AA20C00017)
- Bill and Melinda Gates Foundation (INV-005170, INV-027520)
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases
- NHS Blood and Transplant
- Wellcome Trust (106917/Z/15/Z, 209200/Z/17/Z, Z/17/Z, /Z/15/Z)
- Diamond Light Source
- Leidos
- National Institute for Health and Care Research (209200/Z/17/Z)
- Department of Health and Social Care
- University of Oxford
- European Commission (733273, HORIZON2020)
- National Institutes of Health (106917/Z/15/Z, 209200/Z/17/Z, Z99 AI999999)
- Horizon 2020 Framework Programme (733273)
- Medical Research Council (MR/N013468/1, MR/X012085/1, MR/N013468/)
- Horizon 2020
- National Institute of Allergy and Infectious Diseases
- Office of Extramural Research, National Institutes of Health
- NHLBI Division of Intramural Research
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
- Life Sciences › Immunology and Microbiology › Immunology › Monoclonal and Polyclonal Antibodies Research
- Health Sciences › Medicine › Hematology › Blood groups and transfusion
- Keywords
- PfRH5, Plasmodium falciparum, malaria vaccine, human monoclonal antibodies, epitope specificity, blood-stage malaria
- MeSH terms
- Animals, Antibodies, Monoclonal, Antibodies, Protozoan, Epitopes, Antigens, Protozoan, Carrier Proteins, Erythrocytes, Female, Humans, Immunoglobulin G, Plasmodium falciparum, Protozoan Proteins, Malaria, Falciparum, Malaria Vaccines, Mice
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