Refinement of an ovine-based immunoglobulin therapy against SARS-CoV-2, with comparison of whole IgG versus F(ab′)2 fragments

Stephen Findlay-Wilson; Linda Easterbrook; Sandra Smith; Neville Pope; Matthew Aldridge; Gareth Humphries; Holger Schuhmann; Didier Ngabo; Emma Rayner; Ashley Otter; Thomas Coleman; Bethany Hicks; Rachel Halkerston; Kostis Apostolakis; Stephen Taylor; Susan Fotheringham; Amanda Horton; Irene CanoCejas; Matthew Wand; Julia A. Tree; Mark Sutton; Victoria Graham; Roger Hewson; Stuart Dowall

doi:10.1038/s41598-023-40277-4

Refinement of an ovine-based immunoglobulin therapy against SARS-CoV-2, with comparison of whole IgG versus F(ab′)₂ fragments

Stephen Findlay-Wilson, Linda Easterbrook, Sandra Smith, Neville Pope, Matthew Aldridge, Gareth Humphries, Holger Schuhmann, Didier Ngabo, Emma Rayner, Ashley Otter, Thomas Coleman, Bethany Hicks, Rachel Halkerston, Kostis Apostolakis, Stephen Taylor, Susan Fotheringham, Amanda Horton, Irene CanoCejas, Matthew Wand, Julia A. TreeMark Sutton, Victoria Graham, Roger Hewson, Stuart Dowall^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

The development of new therapies against SARS-CoV-2 is required to extend the toolkit of intervention strategies to combat the global pandemic. In this study, hyperimmune plasma from sheep immunised with whole spike SARS-CoV-2 recombinant protein has been used to generate candidate products. In addition to purified IgG, we have refined candidate therapies by removing non-specific IgG via affinity binding along with fragmentation to eliminate the Fc region to create F(ab′)₂ fragments. These preparations were evaluated for in vitro activity and demonstrated to be strongly neutralising against a range of SARS-CoV-2 strains, including Omicron B2.2. In addition, their protection against disease manifestations and viral loads were assessed using a hamster SARS-CoV-2 infection model. Results demonstrated protective effects of both IgG and F(ab′)₂, with the latter requiring sequential dosing to maintain in vivo activity due to rapid clearance from the circulation.

Original language	English
Article number	13912
Journal	Scientific Reports
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41598-023-40277-4
Publication status	Published - Dec 2023

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© 2023, Springer Nature Limited.

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Findlay-Wilson, S., Easterbrook, L., Smith, S., Pope, N., Aldridge, M., Humphries, G., Schuhmann, H., Ngabo, D., Rayner, E., Otter, A., Coleman, T., Hicks, B., Halkerston, R., Apostolakis, K., Taylor, S., Fotheringham, S., Horton, A., CanoCejas, I., Wand, M., ... Dowall, S. (2023). Refinement of an ovine-based immunoglobulin therapy against SARS-CoV-2, with comparison of whole IgG versus F(ab′)₂ fragments. Scientific Reports, 13(1), Article 13912. https://doi.org/10.1038/s41598-023-40277-4

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title = "Refinement of an ovine-based immunoglobulin therapy against SARS-CoV-2, with comparison of whole IgG versus F(ab′)2 fragments",

abstract = "The development of new therapies against SARS-CoV-2 is required to extend the toolkit of intervention strategies to combat the global pandemic. In this study, hyperimmune plasma from sheep immunised with whole spike SARS-CoV-2 recombinant protein has been used to generate candidate products. In addition to purified IgG, we have refined candidate therapies by removing non-specific IgG via affinity binding along with fragmentation to eliminate the Fc region to create F(ab′)2 fragments. These preparations were evaluated for in vitro activity and demonstrated to be strongly neutralising against a range of SARS-CoV-2 strains, including Omicron B2.2. In addition, their protection against disease manifestations and viral loads were assessed using a hamster SARS-CoV-2 infection model. Results demonstrated protective effects of both IgG and F(ab′)2, with the latter requiring sequential dosing to maintain in vivo activity due to rapid clearance from the circulation.",

author = "Stephen Findlay-Wilson and Linda Easterbrook and Sandra Smith and Neville Pope and Matthew Aldridge and Gareth Humphries and Holger Schuhmann and Didier Ngabo and Emma Rayner and Ashley Otter and Thomas Coleman and Bethany Hicks and Rachel Halkerston and Kostis Apostolakis and Stephen Taylor and Susan Fotheringham and Amanda Horton and Irene CanoCejas and Matthew Wand and Tree, {Julia A.} and Mark Sutton and Victoria Graham and Roger Hewson and Stuart Dowall",

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doi = "10.1038/s41598-023-40277-4",

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Findlay-Wilson, S, Easterbrook, L, Smith, S, Pope, N, Aldridge, M, Humphries, G, Schuhmann, H, Ngabo, D, Rayner, E, Otter, A, Coleman, T, Hicks, B, Halkerston, R, Apostolakis, K, Taylor, S, Fotheringham, S, Horton, A, CanoCejas, I, Wand, M , Tree, JA, Sutton, M, Graham, V, Hewson, R & Dowall, S 2023, 'Refinement of an ovine-based immunoglobulin therapy against SARS-CoV-2, with comparison of whole IgG versus F(ab′)₂ fragments', Scientific Reports, vol. 13, no. 1, 13912. https://doi.org/10.1038/s41598-023-40277-4

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AU - Aldridge, Matthew

AU - Humphries, Gareth

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AU - Otter, Ashley

AU - Coleman, Thomas

AU - Hicks, Bethany

AU - Halkerston, Rachel

AU - Apostolakis, Kostis

AU - Taylor, Stephen

AU - Fotheringham, Susan

AU - Horton, Amanda

AU - CanoCejas, Irene

AU - Wand, Matthew

AU - Tree, Julia A.

AU - Sutton, Mark

AU - Graham, Victoria

AU - Hewson, Roger

AU - Dowall, Stuart

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Refinement of an ovine-based immunoglobulin therapy against SARS-CoV-2, with comparison of whole IgG versus F(ab′)₂ fragments

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