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

改进以绵羊为基础的针对 SARS-CoV-2 的免疫球蛋白疗法,并比较整个 IgG 与 F(ab')2 片段

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作者: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 CanoCej

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.

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