Wang, Lawrence T, Cooper, Andrew J R, Farrell, Brendan et al. (34 more authors) (2024) Natural malaria infection elicits rare but potent neutralizing antibodies to the blood-stage antigen RH5. Cell. 4981-4995.e14. ISSN 1097-4172
Abstract
Plasmodium falciparum reticulocyte-binding protein homolog 5 (RH5) is the most advanced blood-stage malaria vaccine candidate and is being evaluated for efficacy in endemic regions, emphasizing the need to study the underlying antibody response to RH5 during natural infection, which could augment or counteract responses to vaccination. Here, we found that RH5-reactive B cells were rare, and circulating immunoglobulin G (IgG) responses to RH5 were short-lived in malaria-exposed Malian individuals, despite repeated infections over multiple years. RH5-specific monoclonal antibodies isolated from eight malaria-exposed individuals mostly targeted non-neutralizing epitopes, in contrast to antibodies isolated from five RH5-vaccinated, malaria-naive UK individuals. However, MAD8-151 and MAD8-502, isolated from two malaria-exposed Malian individuals, were among the most potent neutralizers out of 186 antibodies from both cohorts and targeted the same epitopes as the most potent vaccine-induced antibodies. These results suggest that natural malaria infection may boost RH5-vaccine-induced responses and provide a clear strategy for the development of next-generation RH5 vaccines.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © Wang et al., 2024 |
Keywords: | malaria,monoclonal antibodies,natural infection,Plasmodium falciparum,RH5,vaccine design |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Hull York Medical School (York) The University of York > Faculty of Sciences (York) > Biology (York) The University of York > Faculty of Sciences (York) > Electronic Engineering (York) |
Depositing User: | Pure (York) |
Date Deposited: | 01 Aug 2024 11:10 |
Last Modified: | 05 Mar 2025 08:30 |
Published Version: | https://doi.org/10.1016/j.cell.2024.06.037 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1016/j.cell.2024.06.037 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:215642 |