Douglas, Alexander D, Baldeviano, G Christian, Jin, Jing et al. (16 more authors) (2019) A defined mechanistic correlate of protection against Plasmodium falciparum malaria in non-human primates. Nature Communications. 1953. ISSN 2041-1723
Abstract
Malaria vaccine design and prioritization has been hindered by the lack of a mechanistic correlate of protection. We previously demonstrated a strong association between protection and merozoite-neutralizing antibody responses following vaccination of non-human primates against Plasmodium falciparum reticulocyte binding protein homolog 5 (PfRH5). Here, we test the mechanism of protection. Using mutant human IgG1 Fc regions engineered not to engage complement or FcR-dependent effector mechanisms, we produce merozoite-neutralizing and non-neutralizing anti-PfRH5 chimeric monoclonal antibodies (mAbs) and perform a passive transfer-P. falciparum challenge study in Aotus nancymaae monkeys. At the highest dose tested, 6/6 animals given the neutralizing PfRH5-binding mAb c2AC7 survive the challenge without treatment, compared to 0/6 animals given non-neutralizing PfRH5-binding mAb c4BA7 and 0/6 animals given an isotype control mAb. Our results address the controversy regarding whether merozoite-neutralizing antibody can cause protection against P. falciparum blood-stage infections, and highlight the quantitative challenge of achieving such protection.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Keywords: | parasites and microbes,staffpaper |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Biology (York) The University of York > Faculty of Sciences (York) > Hull York Medical School (York) |
Depositing User: | Pure (York) |
Date Deposited: | 20 Oct 2020 11:00 |
Last Modified: | 16 Oct 2024 17:01 |
Published Version: | https://doi.org/10.1038/s41467-019-09894-4 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1038/s41467-019-09894-4 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:166928 |