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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-08-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-40277-4 |
| _version_ | 1797452936552382464 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Stephen Findlay-Wilson |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T15:15:53Z |
| format | Article |
| id | doaj.art-b6dbbe9b29a843fc82dd0a936c9ba647 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-09T15:15:53Z |
| publishDate | 2023-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-b6dbbe9b29a843fc82dd0a936c9ba6472023-11-26T13:06:08ZengNature PortfolioScientific Reports2045-23222023-08-0113111410.1038/s41598-023-40277-4Refinement of an ovine-based immunoglobulin therapy against SARS-CoV-2, with comparison of whole IgG versus F(ab′)2 fragmentsStephen Findlay-Wilson0Linda Easterbrook1Sandra Smith2Neville Pope3Matthew Aldridge4Gareth Humphries5Holger Schuhmann6Didier Ngabo7Emma Rayner8Ashley Otter9Thomas Coleman10Bethany Hicks11Rachel Halkerston12Kostis Apostolakis13Stephen Taylor14Susan Fotheringham15Amanda Horton16Irene CanoCejas17Matthew Wand18Julia A. Tree19Mark Sutton20Victoria Graham21Roger Hewson22Stuart Dowall23UK Health Security Agency (UKHSA)UK Health Security Agency (UKHSA)International Therapeutic Proteins LtdInternational Therapeutic Proteins Ltd, Goleigh FarmMicroPharm LtdNative Antigen Company, Langford LocksNative Antigen Company, Langford LocksUK Health Security Agency (UKHSA)UK Health Security Agency (UKHSA)UK Health Security Agency (UKHSA)UK Health Security Agency (UKHSA)UK Health Security Agency (UKHSA)UK Health Security Agency (UKHSA)UK Health Security Agency (UKHSA)UK Health Security Agency (UKHSA)UK Health Security Agency (UKHSA)UK Health Security Agency (UKHSA)UK Health Security Agency (UKHSA)UK Health Security Agency (UKHSA)UK Health Security Agency (UKHSA)UK Health Security Agency (UKHSA)UK Health Security Agency (UKHSA)UK Health Security Agency (UKHSA)UK Health Security Agency (UKHSA)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.https://doi.org/10.1038/s41598-023-40277-4 |
| spellingShingle | 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 Refinement of an ovine-based immunoglobulin therapy against SARS-CoV-2, with comparison of whole IgG versus F(ab′)2 fragments Scientific Reports |
| title | Refinement of an ovine-based immunoglobulin therapy against SARS-CoV-2, with comparison of whole IgG versus F(ab′)2 fragments |
| title_full | Refinement of an ovine-based immunoglobulin therapy against SARS-CoV-2, with comparison of whole IgG versus F(ab′)2 fragments |
| title_fullStr | Refinement of an ovine-based immunoglobulin therapy against SARS-CoV-2, with comparison of whole IgG versus F(ab′)2 fragments |
| title_full_unstemmed | Refinement of an ovine-based immunoglobulin therapy against SARS-CoV-2, with comparison of whole IgG versus F(ab′)2 fragments |
| title_short | Refinement of an ovine-based immunoglobulin therapy against SARS-CoV-2, with comparison of whole IgG versus F(ab′)2 fragments |
| title_sort | refinement of an ovine based immunoglobulin therapy against sars cov 2 with comparison of whole igg versus f ab 2 fragments |
| url | https://doi.org/10.1038/s41598-023-40277-4 |
| work_keys_str_mv | AT stephenfindlaywilson refinementofanovinebasedimmunoglobulintherapyagainstsarscov2withcomparisonofwholeiggversusfab2fragments AT lindaeasterbrook refinementofanovinebasedimmunoglobulintherapyagainstsarscov2withcomparisonofwholeiggversusfab2fragments AT sandrasmith refinementofanovinebasedimmunoglobulintherapyagainstsarscov2withcomparisonofwholeiggversusfab2fragments AT nevillepope refinementofanovinebasedimmunoglobulintherapyagainstsarscov2withcomparisonofwholeiggversusfab2fragments AT matthewaldridge refinementofanovinebasedimmunoglobulintherapyagainstsarscov2withcomparisonofwholeiggversusfab2fragments AT garethhumphries refinementofanovinebasedimmunoglobulintherapyagainstsarscov2withcomparisonofwholeiggversusfab2fragments AT holgerschuhmann refinementofanovinebasedimmunoglobulintherapyagainstsarscov2withcomparisonofwholeiggversusfab2fragments AT didierngabo refinementofanovinebasedimmunoglobulintherapyagainstsarscov2withcomparisonofwholeiggversusfab2fragments AT emmarayner refinementofanovinebasedimmunoglobulintherapyagainstsarscov2withcomparisonofwholeiggversusfab2fragments AT ashleyotter refinementofanovinebasedimmunoglobulintherapyagainstsarscov2withcomparisonofwholeiggversusfab2fragments AT thomascoleman refinementofanovinebasedimmunoglobulintherapyagainstsarscov2withcomparisonofwholeiggversusfab2fragments AT bethanyhicks refinementofanovinebasedimmunoglobulintherapyagainstsarscov2withcomparisonofwholeiggversusfab2fragments AT rachelhalkerston refinementofanovinebasedimmunoglobulintherapyagainstsarscov2withcomparisonofwholeiggversusfab2fragments AT kostisapostolakis refinementofanovinebasedimmunoglobulintherapyagainstsarscov2withcomparisonofwholeiggversusfab2fragments AT stephentaylor refinementofanovinebasedimmunoglobulintherapyagainstsarscov2withcomparisonofwholeiggversusfab2fragments AT susanfotheringham refinementofanovinebasedimmunoglobulintherapyagainstsarscov2withcomparisonofwholeiggversusfab2fragments AT amandahorton refinementofanovinebasedimmunoglobulintherapyagainstsarscov2withcomparisonofwholeiggversusfab2fragments AT irenecanocejas refinementofanovinebasedimmunoglobulintherapyagainstsarscov2withcomparisonofwholeiggversusfab2fragments AT matthewwand refinementofanovinebasedimmunoglobulintherapyagainstsarscov2withcomparisonofwholeiggversusfab2fragments AT juliaatree refinementofanovinebasedimmunoglobulintherapyagainstsarscov2withcomparisonofwholeiggversusfab2fragments AT marksutton refinementofanovinebasedimmunoglobulintherapyagainstsarscov2withcomparisonofwholeiggversusfab2fragments AT victoriagraham refinementofanovinebasedimmunoglobulintherapyagainstsarscov2withcomparisonofwholeiggversusfab2fragments AT rogerhewson refinementofanovinebasedimmunoglobulintherapyagainstsarscov2withcomparisonofwholeiggversusfab2fragments AT stuartdowall refinementofanovinebasedimmunoglobulintherapyagainstsarscov2withcomparisonofwholeiggversusfab2fragments |