Debski-Antoniak, O., Flynn, A., Klebl, D.P. et al. (6 more authors) (2024) Exploiting the Affimer platform against influenza A virus. mBio. ISSN 2161-2129
Abstract
Influenza A virus (IAV) is well known for its pandemic potential. While current surveillance and vaccination strategies are highly effective, therapeutic approaches are often short-lived due to the high mutation rates of IAV. Recently, monoclonal antibodies (mAbs) have emerged as a promising therapeutic approach, both against current strains and future IAV pandemics. In addition to mAbs, several antibody-like alternatives exist, which aim to improve upon mAbs. Among these, Affimers stand out for their short development time, high expression levels in Escherichia coli, and animal-free production. In this study, we utilized the Affimer platform to isolate and produce specific and potent inhibitors of IAV. Using a monomeric version of the IAV trimeric hemagglutinin (HA) fusion protein, we isolated 12 Affimers that inhibit IAV infection in vitro. Two of these Affimers were characterized in detail and exhibited nanomolar-binding affinities to the target H3 HA protein, specifically binding to the HA1 head domain. Cryo-electron microscopy (cryo-EM), employing a novel spray approach to prepare cryo-grids, allowed us to image HA-Affimer complexes. Combined with functional assays, we determined that these Affimers inhibit IAV by blocking the interaction of HA with the host-cell receptor, sialic acid. Furthermore, these Affimers inhibited IAV strains closely related to the one used for their isolation. Overall, our results support the use of Affimers as a viable alternative to existing targeted therapies for IAV and highlight their potential as diagnostic reagents.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2024 Debski-Antoniak et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. |
Keywords: | influenza A virus, Affimer, mAb, cryo-electron microscopy sample preparation |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) |
Funding Information: | Funder Grant number Academy of Medical Sciences SBF002\1029 Wellcome Trust 221524/Z/20/Z Rosetrees Trust A1618 |
Depositing User: | Symplectic Publications |
Date Deposited: | 27 Jun 2024 14:52 |
Last Modified: | 07 Aug 2024 14:15 |
Status: | Published online |
Publisher: | American Society for Microbiology |
Identification Number: | 10.1128/mbio.01804-24 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:213990 |
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