The US government’s medical research arm is preparing the ground for Covid-19 “human challenge trials” that would deliberately infect healthy volunteers with coronavirus, as part of efforts to accelerate work on the development of a vaccine.
Francis Collins, director of National Institutes of Health, has asked the NIH vaccines working group to “write a perspective on the scientific and practical considerations for a Covid-19 human challenge model”.
The group, which includes senior vaccine developers from universities and industry, will meet on May 11 to discuss the issue.
Challenge trials have a long history in medicine because deliberately infecting volunteers gives results more quickly than waiting for them to be infected in the community, but they are inevitably risky.
A growing number of scientists say the world needs a Covid-19 vaccine so urgently that regulators and research funders should make preparations now, enabling human infection studies to begin after potential vaccines have completed their initial safety testing.
Around 100 Covid-19 vaccines are currently in development worldwide, with several in the early stages of clinical trials.
Volunteers are unlikely to be in short supply — more than 14,000 have already signed up on an online register run by the US-based vaccine advocacy group 1DaySooner.
Political support is also growing. Last month 35 members of Congress signed a letter written by their colleagues Bill Foster and Donna Shalala to the Commissioner of the Food and Drug Administration and Secretary of Health and Human Services, urging them to speed up the approval and deployment of a Covid-19 vaccine, including the use of challenge trials.
“We wanted to let the regulators know that we in Congress understand the justifiable risks involved in human challenge trials,” said Mr Foster. “They may be essential if we want to sort through realistic vaccine candidates to find the one that works best — or as an insurance if something goes wrong and the first vaccines don’t work as well as we hope, or if the virus mutates and we have to identify rapidly the best alternatives.”
The pharmaceutical industry would be supportive. Paul Stoffels, chief scientist at Johnson & Johnson, said his company would consider using a human challenge trial for its Covid-19 vaccine to speed up the process, if such a study was accepted by ethicists.
J&J has done human challenge trials with other vaccines, including for the common cold, influenza, and RSV, a respiratory infection that mainly affects premature babies and the elderly.
But Dr Stoffels warned that deliberately infecting people was “very challenging” without a drug or antibody therapy to treat the disease. “If the ethical committees, or the ethical world accepts that is do-able, we will join,” he said. “But we are not counting on it at the moment.”
Dr Stoffels added that it would still take several months for people to research how to manufacture and deliver the virus and what dose to give to infect a human.
The FDA said in a statement: “Human challenge studies are a way to expedite the development of a vaccine to prevent Covid-19. Because these studies involve exposing volunteers to the virus, the studies raise a variety of potential scientific, feasibility, and ethical issues.
“The FDA will work with those who are interested in conducting human challenge trials to help them evaluate these issues.”
Its regulatory counterpart across the Atlantic, the European Medicines Agency, is also potentially supportive. “Human challenge trials could be very helpful in various parts of the vaccine development process and could provide useful information to regulators,” said Marco Cavaleri, EMA’s head of vaccines strategy.
But such studies must provide not only volunteers but also the professionals looking after them with maximum protection against any harm from infection, including possible long-term consequences, Dr Cavaleri said.
The World Health Organization has just issued a 19-page paper outlining the “key criteria for the ethical acceptability of Covid-19 human challenge studies”. Among many other things, it says initial studies should be limited to healthy young adults aged 18 to 30, in whom fatal infection rates are currently estimated at about 0.03 per cent.
So far the discussion of Covid-19 human challenge trials “has been driven almost entirely by the altruism of potential volunteer advocates and the intense considerations of bioethicists”, according to a paper prepared for the NIH vaccines working group. It says the next stage must be to prepare the operational and logistical details of a trial.
The practical questions range from how to administer the virus to arranging a secure facility where participants and staff would have to stay for at least four weeks while the trial took place.
Then there is the question of what virus to use. The NIH group suggests developing a special “challenge strain” with reduced virulence to administer in challenge trials.