LONDON – The U.K. will become the first country to stage a human challenge trial in which volunteers are deliberately infected with SARS-CoV-2, as a fast route to assessing the effectiveness of COVID-19 vaccines, and to build understanding of what an effective immune response looks like.
The contract research organization Open Orphan plc said it is in advanced negotiations with the U.K. government and other partners for the studies, which are expected to be formally announced next week.
Assuming ethical approval, the study will be run by Dublin-based Open Orphan’s Hvivo subsidiary in London. Hvivo, which has long experience of running challenge trials in other infectious diseases, has Europe’s only quarantine clinic, a 24-bedroom facility, with linked virology lab.
The move has backing from researchers in the U.K., as a way to accelerate development of COVID-19 vaccines.
“[Human challenge studies] are particularly useful when studying infectious diseases for which there is no reliable animal model, or where we have only limited data on the immunobiology of a disease,” said Claire Waddington, clinical lecturer in infectious diseases at Cambridge University.
In addition, it is known exactly when people are exposed to a virus. “The response to infection and the protection of any vaccine used in the model can be directly and accurately investigated,” Waddington said.
Peter Wrighton-Smith, CEO of Oxford Immunotec plc, which is developing a commercial test for assessing the T-cell response to SARS-CoV-2 infection, said there is “absolutely no question” that a human challenge study would make a valuable contribution. “It’s a fantastic development, and will be important in understanding the correlates of protection,” he told BioWorld.
Support for human challenge studies to speed up development of vaccines has been growing since May, when the World Health Organization (WHO) released guidelines on how they should be conducted.
The EMA also has endorsed such trials, saying they could be very helpful in various parts of the vaccine development process and would provide information to speed up regulatory appraisal.
Also in May, Francis Collins, director of the U.S. NIH, called on vaccine developers from industry and universities to draw up a checklist of scientific and practical considerations to be addressed in laying the ground for human challenge trials.
One factor holding things back is that unlike other infections for which challenge trials have been conducted, there is no effective remedy if a volunteer who receives live SARS-CoV-2 virus falls ill.
However, Waddington said greater awareness of the course of the disease and improvements in treatment allay some of that concern. “As we gain more understanding of COVID-19, we are increasingly in a position to identify those people for who COVID-19 infection is a mild illness and these people could safely participate in a controlled human infection study after a thorough medical assessment and consent process,” she said.
The WHO advisory group that drew up the framework for human challenge trials was divided on that matter, with 10 members saying such a trial could begin without a rescue remedy, while nine said it should not begin unless there is a treatment.
The advisory group was unanimous in specifying that the age range of volunteers taking part should be 18 to 25. That raises a further concern, which is that findings in young and healthy volunteers might not be a reliable indicator a vaccine would work in the elderly, or in those with underlying health conditions.
Opinion is divided on that, but there could still be a benefit even if a vaccine proves effective only in younger people.
Waddington noted the value of a human challenge trial is not limited to assessing if a vaccine is protective or not. “[It] could give us some extremely useful information on how the immune system responds to COVID, and what responses are protective, as well as providing a model for early testing of candidate vaccines,” she said.
On the question of what form of SARS-CoV-2 volunteers should be exposed to, the WHO’s advisory group concluded two separate isolates should be selected from clade B1, which is circulating in North America and Europe, and two isolates from clade A, the original outbreak strain that circulated in China. A list of isolates has been drawn up from which to select the challenge trial virus.
The OneDaySooner campaign, set up to recruit volunteers for human challenge trials, congratulated the U.K. government on its plans, saying it is glad to have had the opportunity to provide input into the preparations. “We hope and expect that volunteer voices will be further incorporated into publicly available protocols for these studies,” campaigners said in a statement.
OneDaySooner has signed up 37,254 volunteers in 162 countries. It now intends to launch a petition calling for the setting up of a challenge study center that can house 100 to 200 trial participants.