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.

Details

Title
Refinement of an ovine-based immunoglobulin therapy against SARS-CoV-2, with comparison of whole IgG versus F(ab′)2 fragments
Author
Findlay-Wilson, Stephen 1 ; Easterbrook, Linda 1 ; Smith, Sandra 2 ; Pope, Neville 3 ; Aldridge, Matthew 4 ; Humphries, Gareth 5 ; Schuhmann, Holger 5 ; Ngabo, Didier 1 ; Rayner, Emma 1 ; Otter, Ashley 1 ; Coleman, Thomas 1 ; Hicks, Bethany 1 ; Halkerston, Rachel 1 ; Apostolakis, Kostis 1 ; Taylor, Stephen 1 ; Fotheringham, Susan 1 ; Horton, Amanda 1 ; CanoCejas, Irene 1 ; Wand, Matthew 1 ; Tree, Julia A. 1 ; Sutton, Mark 1 ; Graham, Victoria 1 ; Hewson, Roger 1 ; Dowall, Stuart 1 

 UK Health Security Agency (UKHSA), Salisbury, Wiltshire, UK (GRID:grid.515304.6) (ISNI:0000 0005 0421 4601) 
 International Therapeutic Proteins Ltd, Longford, Australia (GRID:grid.515304.6) 
 International Therapeutic Proteins Ltd, Goleigh Farm, Selborne, UK (GRID:grid.423441.4) 
 MicroPharm Ltd, Newcastle Emlyn, UK (GRID:grid.423441.4) 
 Langford Locks, Native Antigen Company, Kidlington, Oxford, UK (GRID:grid.423441.4) 
Pages
13912
Publication year
2023
Publication date
2023
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2857166565
Copyright
© Springer Nature Limited 2023. corrected publication 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.