Development of a natural transmission model of COVID-19

Animal models form an important component to the assessment of vaccine and therapeutics, as currently no suitable alternatives exist. The emergence of SARS-CoV-2 led to models used for SARS-CoV to be assessed as a priority, including ferrets and non-human primates. These models demonstrate viral infection in the respiratory system, but with minor clinical effects. Recent results from China have demonstrated that hamsters develop a wider range of clinical disease signs, as well as virus shedding and pathological changes in respiratory tissues. With the increased disease severity and smaller size, they offer an opportunity for the testing of interventions using a rodent model which is ethically more acceptable than the use of larger non-rodent models. In addition, there is mounting evidence that they shed virus to their cagemates, which offers a challenge route that closely resembles natural infection. Therefore, this proposal will establish the hamster model within the UK for the use of testing interventions and evaluating differences between virus strains.

For the assessment of interventions against COVID-19, there are currently no alternatives to the use of animal systems that fully recapitulate a whole functioning body system. The initial focus on in vivo models for COVID-19, based on experiences of establishing animal models for the pathogenic coronaviruses which cause SARS and MERS, were with ferret and non-human primate models. However, recent results from international laboratories working on SARS-CoV-2 have highlighted that hamsters show a more distinctive COVID-19 disease with clinical signs associated with respiratory infection (rapid breathing, weight loss, ruffled fur). In addition to the clinical signs, hamsters have also been shown to shed SARS-CoV-2 and infect their naïve cage mates. Developing the means of establishing and investigating this natural challenge model will provide important and beneficial testing protocols that can be used evaluate prophylactic therapies and vaccines via a natural infection route under experimental conditions, within a carefully controlled containment level 3 (CL3) envelope. This capability will also enable investigations on transmissibility between animals and studies on different strains, including those SARS-CoV-2 viruses that may be engineered by molecular virology techniques to address questions on virus host interactions. Hamsters appear to offer a valuable disease model for COVID-19. Importantly, establishing the hamster model and associated techniques to evaluate interventions in the UK at the unique CL3 facilities of PHE-Porton, will also support a rapid intervention screening and in vivo research hub for the country on COVID-19. This will support UK industry and academia's research need's and evidence base to progress into clinical trials.