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

Lead Research Organisation: Public Health England
Department Name: UNLISTED

Abstract

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.

Technical Summary

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.
 
Description Mechanism of SARS-CoV-2 Vaccine Enhanced Disease, funded by PHE Studentship competition
Amount £100,000 (GBP)
Organisation Public Health England 
Sector Public
Country United Kingdom
Start 08/2021 
End 09/2024
 
Description Collaboration with Quentin Sattentau`s lab in Oxford 
Organisation University of Oxford
Department Oxford University Innovation
Country United Kingdom 
Sector Private 
PI Contribution A member of our team worked in Quentin Sattentau`s lab for two months learning the relevant ELISA technique. They then brought this back to our lab in Oxford.
Collaborator Contribution Quentin Sattentau`s lab trained members of staff and performed a number of assays looking into antibody binding to formulin inactivated spike protein.
Impact Training in ELISA procedure. Assistance writing manuscript on Vaccine enhanced disease.
Start Year 2021
 
Description Twitter based discussion related to vaccine hesitancy 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact IN response to a vaccine hesitancy view on the danger of vaccine enhanced disease for COVID-19 vaccines. Our work was presented as a key study to illustrate VED had not been observed in NHP vaccine studies.
Year(s) Of Engagement Activity 2021
 
Description World Health Organisation COVID-19 R&D Road Map: In vivo models working group 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The work was presented before publication to the working group which sparked discussion on COVID vaccine safety. Regulators were also present and this information helped them to understand the relative risks of enhanced diseases associated with novel COVID-19 vaccine candidates.
Year(s) Of Engagement Activity 2020