Ferret chosen as animal model to test coronavirus vaccines

A team led by India-born virologist Seshadri Vasan has established an animal model – the ferret – as a preclinical model to test COVID-19 vaccines and therapies.

Vasan, who holds an honorary chair in Health Sciences at the University of York, UK, leads the Dangerous Pathogens team at the Australian Animal Health Laboratory and is senior principal research consultant for Health and Biosecurity at the Commonwealth Scientific and Industrial Research Organization (CSIRO), Australia's national science agency.

His team has shown that ferrets (Mustela putorius furo) – the domesticated form of the European polecat – could be used as a preclinical model for COVID-19 vaccine and therapies. Ferrets are a popular model for influenza and other respiratory infections because their lung physiology is similar to that of humans, and researchers hope they will mimic aspects of COVID-19 in people, such as its spread. Vasan, who is currently based at the high-containment laboratory in Geelong, Australia, has found that the animals are susceptible to SARS-CoV-2.

There are many vaccines¹ for COVID-19 under development of which eight are funded by The Coalition for Epidemic Preparedness Innovations (CEPI), a foundation that takes donations from philanthropic, and civil society organisations to finance independent projects to develop vaccines against emerging infectious disease.

Although provocative questions² like "should scientists infect healthy people with the coronavirus to test vaccines?" are being asked, the regulatory route usually mandates animal efficacy data before human efficacy data can be collected in Phase 2 and Phase 3 trials.

"In this context, my team was the first to show ferrets are susceptible³ and we have now started what are probably the world's first animal studies involving multiple vaccines," Vasan told Nature India . The Australian government has announced it will provide $220 million to upgrade CSIRO bio-security research facility in Geelong to help better understand the coronavirus and test potential vaccines. The preclinical research by Vasan's team is funded by a partnership between CSIRO and CEPI.

Two of the candidate vaccines we are testing are University of Oxford's viral vectored vaccine and the DNA vaccine of Pennsylvania-based Inovio Pharmaceuticals ", Vasan who is the Principal Investigator of the CEPI projects said. "These two are due to enter Phase-1 clinical trials with healthy volunteers," Vasan said. "But before they can advance to Phase 2, it will be necessary to complete efficacy testing in animals and therefore CEPI has funded us to run the world’s first multi-vaccine efficacy studies in animals.

Vasan's team has grown the virus for this work. “Having demonstrated that ferrets are susceptible to this virus, we have designed a staggered challenge study to get timely information on vaccine efficacy, initially with just the prime dose, followed closely by prime and boost doses," Vasan said. Oxford’s vaccine is currently being designed as an intramuscular injection. Vasan said his team intends to additionally investigate if giving it through the nose (intranasally) would confer additional protection due to mucosal immunity, and whether one or two doses will be necessary for Oxford’s vectored vaccine and Inovio’s DNA vaccine.

University of York, in a press release, quoted the Chair of CEPI, Jane Halton, as saying "this is the first time that we’ve done these animal model tests to look at two candidate vaccines for both of which the CEPI coalition has provided funding." CEPI vice-chair Gagandeep Kang said they were hoping the project moves fast and the challenge studies in ferrets can be done. "They have been very useful for influenza vaccines and could advance the development of SARS-CoV-2 vaccines," she told Nature India .

“The virus strain can be currently organised into three major clusters, with more emerging,” Vasan said. Some of the mutations in the virus may be significant for the development and evaluation of new diagnostics, drugs and vaccines. “So it is very important for us to understand it,” Vasan added. He said his team is also investigating the physical and molecular characterisation of the virus to find differences and similarities with other known coronaviruses.

[Nature India's latest coverage on the novel coronavirus and COVID-19 pandemic here . More updates on the global crisis here .]

References

1. Hidgson, J. The pandemic pipeline. Nat. Biotechnol. (2020) doi: 10.1038/d41587-020-00005-z

2. Callaway, E. Should scientists infect healthy people with the coronavirus to test vaccines? Nature 580, 17 (2020) doi: 10.1038/d41586-020-00927-3

3. Callaway, E. Labs rush to study coronavirus in transgenic animals — some are in short supply. Nature 579, 183 (2020) doi: 10.1038/d41586-020-00698-x