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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 intentional exposure to the virus and blazing a new and uncertain path. to identify an effective vaccine. .
The highly controversial strategy, known as a human challenge test, could potentially cut a crucial time in the race to winnow a series of vaccine candidates. Rather than conducting the kinds of trials that are taking place around the world, in which scientists wait for vaccinated people to find the virus in their homes and communities, researchers would intentionally infect them in a hospital isolation unit. .
Scientists have used this method for decades to test vaccines against 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 while those infected could be cured of those diseases, Covid-19 has few widely used treatments and no known cures, putting the scientists in charge of Britain’s study in largely unexplored ethical territory.
Starting with small doses, scientists will first administer the virus to small groups of volunteers who have not been vaccinated at all, 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 from Imperial College London and hVivo, a company specializing in human challenge trials. It still requires approval from Britain’s drug regulatory agency, but the government said Tuesday it would allocate 34 million pounds, or $ 44 million, in public funds.
The first round of volunteers, up to 90 healthy adults between the ages of 18 and 30, will have the virus introduced 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 level of virus exposure.
Only once scientists decide on the dose, which they intend to do in 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 candidate vaccines that are undergoing trials may already have been approved by then, but the researchers hope that a challenge test will add direct evidence of efficacy and help them compare the performance of different vaccines.
“Deliberate infection of volunteers with a known human pathogen is never taken lightly,” said Professor Peter Openshaw, an immunologist and co-investigator on the study. “However, these studies are enormously informative about a disease, even one as 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 candidate vaccines to include in the human challenge trial, has yet to announce its plans.
The idea of human challenge trials has already been warmly welcomed by several leading vaccine manufacturers, including Johnson & Johnson and Moderna, leaving analysts unsure which company vaccines will end up being included.
And it is not yet clear how regulators in Europe or the United States will evaluate the results of human challenge trials, or whether such studies will speed up the vaccine approval process.
For proponents of the strategy, saving lives by potentially accelerating vaccine development and advancing understanding of the virus is a moral imperative. Those scientists and bioethicists say the risk of the coronavirus seriously ill or killing young, healthy volunteers – the kind of people who would become infected – is low enough to be outweighed by the possibility of saving tens of thousands of lives. .
“I’m surprised they haven’t been used before,” said Professor Julian Savulescu, director of the Oxford Uehiro Center for Practical Ethics, of human challenge trials with coronavirus vaccines. “Every day that the development of a vaccine and effective treatment is delayed, another 5,000 people die. It would be useful in detecting less effective vaccines and understanding the immune response. “
Skeptics have urged scientists to wait or forgo the approach entirely. There have been unexpected and unexplained cases of severe illness in young patients, and the long-term consequences of an infection are unknown, as the pandemic began only a few months ago. It is also difficult to extrapolate widely from a human challenge assay. It is not clear, for example, whether studies in healthy young adults could reliably predict the efficacy of a vaccine in older adults or people with pre-existing conditions.
Scientists have also warned about the challenges of mimicking real-world transmission in a laboratory. That could make it difficult for researchers to know whether a vaccine that can protect volunteers from deliberate exposure in a hospital would do the same for people who come across the virus at work or at home.
“Is it exhaled, sneezed, do you smell it all in a single piece of virus coming your way?” said John Moore, professor of microbiology and immunology at Weill Cornell Medical College. “Nobody really knows. It is so difficult to model. Spraying a bolus of virus into the nose is an imperfect pattern of natural transmission. “
The debate has divided an advisory panel to the World Health Organization, which published guidelines on the safest way to conduct challenge trials in June. In the United States, the National Institutes of Health said they did not plan to support such trials and that randomized clinical trials were sufficient.
But Britain took a different view.
Prime Minister Boris Johnson, facing a barrage of criticism for his handling of a pandemic that has left Britain with the highest death toll in Europe, has sought to position the country as at the forefront of scientific progress on the coronavirus. Researchers at the University of Oxford have developed one of the leading vaccine candidates, as well as one of the most promising treatments, the steroid dexamethasone.
Some scientists questioned whether fierce competition to be the first to develop an effective vaccine had unduly influenced plans for a challenge trial in humans.
“There is no question that there is a vaccine nationalism involved,” said Professor Moore. “It is a race for money and glory. Thats the reality “.
The scientists who supervised the trial said they would use the antiviral drug remdesivir to treat the volunteers as soon as they began to detect a viral infection, even before the onset of symptoms. But that drug has been found to have only modest benefit. And some analysts said the treatment, while necessary, would limit the researchers’ ability to determine whether the vaccine candidates being tested reduce the severity of the disease.
Volunteers in London will be paid roughly Britain’s minimum wage, which is roughly £ 9, or $ 11, an hour, for the time they have participated in the trial and their two to three weeks in mandatory quarantine. The researchers said they were wary of offering additional incentives that could cloud the volunteers’ judgment.
Thousands of people in Britain have already expressed interest in participating in challenge trials for the coronavirus through a US group, 1Day Sooner, which advocates for such studies.
But now that the virus is on the rise again in Europe and parts of the United States, some scientists have argued that there is no shortage of people enrolled in ordinary vaccine trials who are exposed to the virus under natural conditions.
“This is not a rare disease,” said Dr. Paul Offit, a professor at the University of Pennsylvania and a member of the Food and Drug Administration’s vaccine advisory panel. “You can probably find a hot spot to do a vaccine test.”
