LONDON – In the coming weeks, a small, carefully selected group of volunteers is expected to arrive on the 11th floor of a London hospital to get what the rest of the world’s 7.8 billion people are trying to avoid: a coronavirus infection.
They will inject small droplets of virus into their nostrils as part of a plan approved by British regulators on Wednesday to deliberately infect unvaccinated volunteers with the coronavirus.
The scientists hope to eventually vaccinate people exposed to the virus as a way to compare the effectiveness of different vaccines. But before that, supporters of the project have to expose unvaccinated volunteers to determine the lowest dose of virus they can reliably infect.
By controlling and monitoring the amount of virus that humans undergo from the moment they are infected, scientists hope to discover things about how the immune system responds to the coronavirus that would be impossible outside the laboratory – and to develop ways to directly compare the effectiveness of treatments and vaccines.
“We are going to learn a lot about the immunology of the virus,” said Peter Openshaw, a professor at Imperial College London who was involved on Wednesday. He added that the study “could not only speed up the understanding of diseases caused by infections, but also the discovery of new treatments and vaccines.”
The idea of such a study, called a human challenge test, has been hotly debated since the first months of the pandemic.
In the past, scientists have deliberately exposed volunteers to diseases such as typhus and cholera to test vaccinations. But infected people can be cured of these diseases; Covid-19 has no known remedy, which puts the scientists in charge of the British study in largely unknown ethical realm.
To try and ensure that participants do not become seriously ill, the UK study will be limited to healthy volunteers in the age group 18 to 30.
There have been severe cases of Covid-19, even in such patients, and the long-term consequences of an infection are also unknown. The age restrictions can also make it difficult to translate the findings to older adults or people with pre-existing conditions, whose immune response may be different and what the target group for treatments and vaccinations is.
“This will be a limited study,” said Ian Jones, a professor of virology at the University of Reading who is not part of the study. “And you could argue that by definition it’s not going to study those with whom it’s most important to know what’s going on.”
The only part of the study formally approved by UK regulators is the experiment to determine the lowest dose of virus needed to infect humans.
After the participants are exposed to the virus, they will be isolated in the hospital for two weeks. For that and for the year’s follow-up appointments planned, £ 4,500, or about £ 6,200, will be paid. The researchers said it would compensate people for time away from work or families without creating too great an economic incentive for people to participate.
When the idea of human challenge trials was first pursued last year, some scientists saw it as a way to shave off the important time in the race to identify a vaccine. Unlike in large clinical trials, in which scientists wait for vaccinated people to experience the virus in their communities, researchers in this project will end up deliberately infecting people who have been vaccinated.
Now that several vaccines have been authorized, the objectives of this trial for human challenges are somewhat different.
For now, the researchers will expose people to the version of the virus that has been spreading in Britain since last spring, and not the more contagious and potentially deadly variant that has recently gained more traction. But ultimately, they said, they could give experimental vaccines designed to address the effect of new, worrying variants and then subject them to versions of the virus.
They can also directly compare different vaccine doses and dose ranges for the same vaccine.
And once the pandemic subsides and there are fewer patients in the hospital to enroll in drug trials, the scientists behind the study said that additional such trials where people are directly infected will enable them to continue investigating new treatments.
“In the future, we will not have a large number of people in the field,” said Robert Read, a professor of infectious diseases at the University of Southampton.
Andrew Catchpole, chief scientific officer at hVIVO, a company specializing in human challenge trials involved in the study, can deliver contamination to unvaccinated people with even low doses of the virus.
As intensively as the coronavirus has been studied, relatively little is understood about how people’s immune systems react in the immediate aftermath of infection.
Scientists do not yet know the specific type or level of immune responses needed to protect most people from infection, an idea of how the dozens of vaccines still being studied will perform against the virus.
“One of the things we do not understand is a real protective response,” said Lawrence Young, a virologist at Warwick Medical School who was not involved in the study. “It’s a great way to understand the host-pathogen interaction, although it obviously has a whole bunch of ethical issues.”
In the first part of the study, the scientists will administer small doses of virus to a small group of volunteers. If they do not become infected, the scientists will give slightly larger doses to another group of volunteers and repeat the process up to 90 participants until they have determined the correct dose.
By this spring, scientists hope to repeat a version of their experiment by exposing vaccinated people to the virus. The British government, which is helping to fund the study, will help select the vaccines. These and other future phases of the trial will require new regulatory approvals.
There was no shortage of interest among potential volunteers for this type of trial, and thousands of people around the world registered their interest with 1Day Sooner, a group advocating human challenge trials as a way to accelerate the development of enough vaccines to to vaccinate people. in parts of the world still waiting for doses
It is not clear how drug regulators in Britain or around the world would rate the results of a human challenge test, given the age restrictions and the small number of people involved.
But dr. Catchpole said the UK’s drug regulator had indicated it would take any of the group’s findings into account as it evaluates future vaccine candidates.
Since the virus now produces dangerous mutations, the scientists one question is whether they will be able to keep up with its evolution.
Just as making new vaccines takes time, so does the production of new viral particles to infect humans. Dr Catchpole said it would take three to four months to make a new coronavirus variant in a laboratory before they could start dropping drops of it into the noses of volunteers.