Development of a cost-effective ovine antibody-based therapy against SARS-CoV-2 infection and contribution of antibodies specific to the spike subunit proteins

Autor: Stephen Findlay-Wilson, Linda Easterbrook, Sandra Smith, Neville Pope, Gareth Humphries, Holger Schuhmann, Didier Ngabo, Emma Rayner, Ashley David Otter, Tom Coleman, Bethany Hicks, Victoria Anne Graham, Rachel Halkerston, Kostis Apostolakis, Stephen Taylor, Susan Fotheringham, Amanda Horton, Julia Anne Tree, Matthew Wand, Roger Hewson, Stuart David Dowall
Jazyk: angličtina
Rok vydání: 2022
Předmět:
ISSN: 0166-3542
Popis: Antibodies against SARS-CoV-2 are important to generate protective immunity, with convalescent plasma one of the first therapies approved. An alternative source of polyclonal antibodies suitable for upscaling would be more amendable to regulatory approval and widespread use. In this study, sheep were immunised with SARS-CoV-2 whole spike protein or one of the subunit proteins: S1 and S2. Once substantial antibody titres were generated, plasma was collected and samples pooled for each antigen. Non-specific antibodies were removed via affinity-purification to yield candidate products for testing in a hamster model of SARS-CoV-2 infection. Affinity-purified polyclonal antibodies to whole spike, S1 and S2 proteins were evaluated for in vitro for neutralising activity against SARS-CoV-2 Wuhan-like virus (Australia/VIC01/2020) and a recent variant of concern, B.1.1.529 BA.1 (Omicron), antibody-binding, complement fixation and phagocytosis assays were also performed. All antibody preparations demonstrated an effect against SARS-CoV-2 disease in the hamster model of challenge, with those raised against the S2 subunit providing the most promise. A rapid, cost-effective therapy for COVID-19 was developed which provides a source of highly active immunoglobulin specific to SARS-CoV-2 with multi-functional activity.
Databáze: OpenAIRE