Development of an NHP model of infection and ADE with COVID-19 (SARS-CoV-2)

The three important things that are urgently required to fight SARS-CoV-2 are prevention, and protection & treatment. Prevention is being implemented by screening and self isolation but as the number of countries reporting cases has risen to 29, the lack of a licenced vaccine or therapeutic to protect patients is increasingly important. PHE propose to develop a model of infection to evaluate interventions. Additionally, we need to develop a model to assess safety as there are concerns that some vaccines or treatments may accidentally enhance the disease. We cannot ethically test this in humans and we cannot risk using vaccines without checking that the vaccine or therapy is safe. We know whole virus vaccines against SARS can accidentally make things worse and that vaccines need to be carefully designed to avoid this risk. This project will test if this complication is relevant for SARS-CoV-2 as well as SARS-CoV-1. Once we have established this, we will be able to offer the ability to test for this problem to all vaccine developers or authorities wishing to check this before use in humans.

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.

PHE Porton's extensive experience in the development of high containment infectious disease models will be applied to set up the UK's first primate model of SARS-CoV-2 infection. This will be achieved by intra-tracheal infection using a virus stock of SARS-CoV-2 acquired through international collaboration. PHE's Victoria stock of virus has been propagated in vitro and has already been used to challenge ferrets at PHE Porton. PHE will also assess the ability of a crude (killed whole virus) vaccine to induce immune mediated disease enhancement. This will be achieved by serially immunising NHPs and then infecting them with live SARS-CoV-2. PHE will assess the clinical signs of infection as well as assessing lung pathology in-life through X-ray and/or CT imaging. In this way, if unusal pathology is observed in the immunised groups, PHE will have set up a "positive control" ADE model to help discriminate vaccines or therapies which assist the host or accidentally enhance the immunopathology of acquired infection.