Credit – Getty Images—Jonnie Miles
On Oct. 20, researchers at the Imperial College of London announced plans for the first human challenge study of COVID-19, which involves deliberately infecting volunteers with the virus that causes the disease, in order to test the effectiveness of vaccines.
The strategy is controversial, as researchers have to weigh the risks of infection against the benefits of learning how well the various vaccine candidates can fight that infection. The strongest argument in favor of the studies has to do with time. If cases of COVID-19 are waning, then the likelihood that people who are vaccinated would get exposed to and potentially infected with the virus naturally declines as well, and it takes researchers longer to accumulate enough data to tell if a vaccine is effective or not. By intentionally exposing people to the virus after they have been vaccinated, researchers can shrink this timeline significantly.
Scientists have used the model to test vaccines against a number of different diseases, including the very first one against smallpox—Edward Jenner infected his son with cowpox, and then exposed his son to smallpox as a way to test his theory that exposure to the former would protect his son from infection by the latter. Scientists tested an H1N1 influenza vaccine by exposing people to the flu, and did the same with a cholera vaccine and the bacterium that causes it. But the strategy requires a solid base of information about both the disease and the vaccine in order to justify the risks. More recently, for example, scientists considered intentionally infecting volunteers with the Zika virus to test vaccines against that disease, but ultimately decided they didn’t have enough data to justify the risk.
Adair Richards, honorary associate professor at the University of Warwick who last May published guidelines on how to ethically conduct human challenge studies, notes that during a pandemic, the risk of delays in developing treatments should be considered alongside the risks to volunteers who are intentionally exposed to disease. “There is a moral weight to inaction as well as action,” he says. “There is an unseen risk if we don’t do [these studies]. We send a lot of doctors, nurses and care workers to work every day, and some will get really sick and die of COVID-19 in the next few weeks. [Those] few weeks count—that’s the unseen risk.”
More than 38,000 people in the U.S. agree, and have registered their intention to volunteer for challenge studies on 1DaySooner.org, an online recruiting group—despite the fact that no such studies have been planned in the country yet.
The London-based scientists still need to submit a detailed proposal to regulatory agencies on how they could conduct their study. If the proposal is approved, the team won’t start exposing any volunteers until January. Before that, they will first need to determine what dose of SARS-CoV-2, the virus that causes COVID-19, is safe to give to people but can still produce
LONDON — Scientists at Imperial College London plan to deliberately infect volunteers with the coronavirus early next year, launching the world’s first effort to study how vaccinated people respond to being intentionally exposed to the virus and opening up a new, uncertain path to identifying an effective vaccine.
The hotly contested strategy, known as a human challenge trial, could potentially shave crucial time in the race to winnow a number of vaccine candidates. Rather than conducting the sort of trials now underway around the world, in which scientists wait for vaccinated people to encounter the virus in their homes and communities, researchers would purposely infect them in a hospital isolation unit.
Scientists have used this method for decades to test vaccines for typhoid, cholera and other diseases, even asking volunteers in the case of malaria to expose their arms to boxes full of mosquitoes to be bitten and infected. But whereas the infected could be cured of those diseases, Covid-19 has few widely used treatments and no known cure, putting the scientists in charge of Britain’s study in largely uncharted ethical territory.
Starting with tiny doses, the scientists will first administer the virus to small groups of volunteers who have not been vaccinated at all, in order to determine the lowest dose of the virus that will reliably infect them. That process, scheduled to begin in January at a hospital in north London, will be followed by tests in which volunteers are given a vaccine and then intentionally exposed to this carefully calibrated dose of the virus.
The study will be led by scientists with Imperial College London and hVivo, a company specializing in human challenge trials. It still requires approval from Britain’s drug regulation agency, but the government said on Tuesday that it would allot 34 million pounds, or $44 million, in public funding.
The first round of volunteers, up to 90 healthy adults aged 18 to 30, will have the virus dripped into their noses without having been vaccinated. If not enough participants become infected, the scientists will try to expose these early-stage volunteers to a higher dose, repeating the process until they have identified the necessary exposure level of the virus.
Only once the scientists decide on a dose, which they intend to do by late spring, will they begin the process of comparing vaccine candidates by immunizing the next group of volunteers and then exposing them to the virus.
Some vaccine candidates now undergoing trials may already have received approval by then, but researchers hope a challenge trial will add direct evidence of efficacy and help them compare the performance of different vaccines.
“Deliberately infecting volunteers with a known human pathogen is never undertaken lightly,” said Professor Peter Openshaw, an immunologist and co-investigator on the study. “However, such studies are enormously informative about a disease, even one so well studied as Covid-19.”
Many important questions about the study remain unanswered. The British government’s vaccine task force, which will select the first vaccine candidates to include in