More than £30m of UK government money is to fund the world’s first Covid-19 “challenge trials”, in which healthy young volunteers are intentionally infected with the virus to hasten the development of a vaccine.
The trials have the potential to yield results more quickly than conventional vaccine field trials in which researchers must wait for participants to get infected in the real world.
These studies can also be used to compare multiple vaccine candidates, develop treatments and gather data about the immediate aftermath of infection that would not be possible to procure otherwise.
The use of such trials dates back to the end of the 18th century, when the English physician Edward Jenner inoculated a young boy with cowpox virus and then exposed him to smallpox as part of an effort that led to the world’s first vaccine. Since then, the method has also been used to develop vaccines for typhoid, cholera and malaria.
Some scientists have reservations about exposing volunteers to a virus for which there is no cure, although there are some treatments that have been shown to help, such as the antiviral remdesivir that is proven to reduce the length of a hospital stay and two steroids have been shown to save lives. But proponents argue that the risks of coronavirus to young and healthy people are low and the benefits to society high.
The government has announced it is investing £33.6m to back the studies in partnership with Imperial College London, hVIVO and the Royal Free London NHS foundation trust. The funding includes a contract worth up to £10m signed with hVivo, a subsidiary of Dublin-based pharmaceutical services company Open Orphan, to develop the model for the trial.
The trial will start with a “characterisation study” in January at the Royal Free hospital in London, which will attempt to establish the minimum dose of the virus required to cause a Covid infection in up to 90 white volunteers aged 18 to 30, because they carry the lowest risk. This characterisation study, sponsored by Imperial College London, is pending regulatory and ethical review.
“We’re not trying to make these subjects really sick. In fact, quite the reverse. We’re religiously trying to get just enough that we can detect [the] virus,” said Andrew Catchpole, the chief scientific officer of hVivo. “We could achieve the goal with as much as only 10, 20, maybe even 30 people … and then we can move on to vaccine testing.”
He added that the characterisation study could take between two and four months to complete.
Apart from ensuring volunteers’ immune systems are not overburdened, one key component of the study is choosing the appropriate strain of the virus. The company isolated the strain about four months ago, said Catchpole, emphasising that it continues to represent the strain circulating in the UK population.
The company will get up to £10m to conduct the characterisation study, depending on the number of volunteers used. The government has also secured the first three slots to test vaccines, with each reservation valued at £2.5m, hVivo said.
“Human challenge studies have been ongoing for many years now – they are a useful way in which we can gain an awful lot of information in a relatively short space of time, from few numbers of people,” said Dr Martin Broadstock, the programme manager for vaccines at the Medical Research Council, which is an arm of UK Research and Innovation (UKRI).
On the relative risks of human challenge trials, Katharine Wright, assistant director at the Nuffield Council on Bioethics, noted that they take place to test flu vaccines without there being an effective treatment, and all “first in human” trials similarly present unknown risks.
Despite the uncertainty, volunteers are lining up. More than 2,500 UK volunteers have signed up to the 1Day Sooner movement, which has been petitioning parliament to support human challenge trials and fund a challenge study centre to quarantine between 100 and 200 volunteers. Globally, the non-profit organisation advocating for human challenge study volunteers has attracted over 38,500 willing participants.
“I’m young and healthy. To me, the risks are not insignificant, but small,” said 1Day Sooner volunteer and UK petition organiser Alastair Fraser-Urquhart, who recently deferred his acceptance to study cancer biology at University College London.
“I just don’t think that one or two vaccines are going to be enough to end the pandemic in the next few years. And without challenge trials, I really don’t see a practical path to get in as many vaccines as we need.”
Volunteers are typically compensated for their involvement in challenge trials. It’s normally in the region of about £4,000, said Catchpole, though that is something the ethics committee will decide.
But people were volunteering for altruistic reasons, said Wright. “People are publicly coming forward to volunteer for challenge trials because they want to help everyone return to ordinary life as soon as possible,” she said. “It’s very impressive … but they have to understand that nothing is certain in research.”