Development of an ovine polyclonal immunoglobulin therapy against COVID-19.

This COVID-19 Rapid Response award is jointly funded (50:50) between the Medical Research Council and the National Institute for Health Research. The figure displayed is the total award amount of the two funders combined, with each partner contributing equally towards the project. The new coronavirus disease that emerged in 2019 (COVID-19) is caused by a pathogen termed SARS-CoV-2. To develop a rapid and effective therapy against infection, we are proposing to develop an ovine immunoglobulin treatment against the spike protein of this virus. Binding of antibodies to this protein will neutralise cell entry and prevent it's infectivity. Use of ovine immunoglobulin therapy is widespread for other applications, and a therapy rapidly developed for Ebola virus disease (termed EBOTAb) which demonstrated protection in guinea pigs and non-human primates. The use of polyclonal sera recognising muitiple epitopes eliminates risks of escape mutations occuring and eliminating the effectiveness of antibody therapy. This approach is also rapid, cost-effective and has a proven path to regulatory approval. To develop this therapy, recombinant spike protein will be produced in a mammalian expression system to ensure relevant protein folding and confirmation. A large batch will be produced for immunisation of sheep. Immunisations will be conducted using a facility in Australia, to mitigate risks associated with BSE. Sera will be sent to PHE for assessment of antibody levels and once sufficient antibody levels are achieved, plasmapheresis sampling will be undertaken. Immunoglobulin from these samples will be purified to develop the therapeutic material. This will be characterised at PHE for binding and functional properties before being testing using a susceptible animal model for protection against infection and disease progression.