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

Autor: 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
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Scientific Reports, Vol 13, Iss 1, Pp 1-14 (2023)
Druh dokumentu: article
ISSN: 2045-2322
DOI: 10.1038/s41598-023-40277-4
Popis: 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.
Databáze: Directory of Open Access Journals
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