de Graaf, H., Payne, R.O. orcid.org/0000-0002-8490-671X, Taylor, I. et al. (25 more authors) (2021) Safety and Immunogenicity of ChAd63/MVA Pfs25-IMX313 in a Phase I First-in-Human Trial. Frontiers in Immunology, 12. 694759.
Abstract
Background Transmission blocking vaccines targeting the sexual-stages of the malaria parasite could play a major role to achieve elimination and eradication of malaria. The Plasmodium falciparum Pfs25 protein (Pfs25) is the most clinically advanced candidate sexual-stage antigen. IMX313, a complement inhibitor C4b-binding protein that forms heptamers with the antigen fused to it, improve antibody responses. This is the first time that viral vectors have been used to induce antibodies in humans against an antigen that is expressed only in the mosquito vector. Methods Clinical trial looking at safety and immunogenicity of two recombinant viral vectored vaccines encoding Pfs25-IMX313 in healthy malaria-naive adults. Replication-deficient chimpanzee adenovirus serotype 63 (ChAd63) and the attenuated orthopoxvirus modified vaccinia virus Ankara (MVA), encoding Pfs25-IMX313, were delivered by the intramuscular route in a heterologous prime-boost regimen using an 8-week interval. Safety data and samples for immunogenicity assays were taken at various time-points. Results The reactogenicity of the vaccines was similar to that seen in previous trials using the same viral vectors encoding other antigens. The vaccines were immunogenic and induced both antibody and T cell responses against Pfs25, but significant transmission reducing activity (TRA) was not observed in most volunteers by standard membrane feeding assay. Conclusion Both vaccines were well tolerated and demonstrated a favorable safety profile in malaria-naive adults. However, the transmission reducing activity of the antibodies generated were weak, suggesting the need for an alternative vaccine formulation. Trial Registration Clinicaltrials.gov NCT02532049.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2021 de Graaf, Payne, Taylor, Miura, Long, Elias, Zaric, Minassian, Silk, Li, Poulton, Baker, Draper, Gbesemete, Brendish, Martins, Marini, Mekhaiel, Edwards, Roberts, Vekemans, Moyle, Faust, Berrie, Lawrie, Hill, Hill and Biswas. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY)(https://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
Keywords: | Pfs25; malaria; transmission-blocking; IMX313; vaccine |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Infection and Immunity (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 25 Jul 2021 22:59 |
Last Modified: | 25 Jul 2021 22:59 |
Status: | Published |
Publisher: | Frontiers Media SA |
Refereed: | Yes |
Identification Number: | 10.3389/fimmu.2021.694759 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:176474 |