Healthy, young volunteers who previously fought off Covid-19 will be deliberately exposed to the virus for a second time in a trial at the University of Oxford that may shed light on how to develop more effective vaccines.
Researchers are looking for 64 healthy, previously Covid-infected volunteers aged 18 to 30 to be studied under controlled, quarantined conditions for at least 17 days, the UK university said on Monday. Participants will be infected with the original strain from Wuhan, China and analysed for a year.
The “human challenge” trial aims to determine what dose of virus is needed to re-infect after natural infection, how the immune system responds and what this could mean for developing protective immunity against the disease.
The study is funded by the Wellcome Trust and is expected to start this month after receiving ethics approval.
Human challenge studies have played a key role in furthering the development of treatments for diseases such as malaria, TB, typhoid, cholera and flu.
A similar study is ongoing in the UK where volunteers are being infected with coronavirus to test vaccines and treatments.
Helen McShane, professor of vaccinology at the department of paediatrics, University of Oxford and chief investigator on the study, said: “Challenge studies tell us things that other studies cannot because, unlike natural infection, they are tightly controlled.
“When we reinfect these participants, we will know exactly how their immune system has reacted to the first Covid infection, exactly when the second infection occurs, and exactly how much virus they got.
“As well as enhancing our basic understanding, this may help us to design tests that can accurately predict whether people are protected.”
Initial data from the Oxford study should be available within several months, helping vaccine developers look at levels and types of immunity needed to prevent reinfection, and how long protection persists. Challenge trials, involving deliberate, supervised infections, are seen as particularly helpful for answering questions like these, because they allow scientists to scrutinise the details of how the body confronts the virus and vice versa.
While vaccines and previous infections provide some immune protection against the coronavirus, concerns and doubts remain about how long it lasts. A recent study indicated that as much as 10 per cent of previously infected young adults were reinfected, underscoring the need for effective vaccines to prevent spread, and Pfizer's chief executive officer has said that booster shots may be needed to maintain the immunity provided by the two doses of the company’s drug.
The Oxford study “has the potential to transform our understanding by providing high-quality data on how our immune system responds to a second infection,” said Shobana Balasingam, a research adviser at the Wellcome Trust. The findings could “inform not just vaccine development but also research into the range of effective treatments that are also urgently needed.”
One of the goals of the study is to determine how much virus, on average, it takes to infect someone who’s already had the virus. In a second phase of the study, a different group of patients will be given that dose and studied for their immune responses, Oxford said.
The earliest volunteers in the world’s first human challenge trial involving the coronavirus, conducted by Imperial College in London, left quarantine in late March. That trial, which intentionally infected people who hadn’t previously had the virus, was backed by £33.6m ($46.3m) of UK government funding.
Critics of challenge trials have pointed out the ethical dangers of infecting people without being sure of long-term consequences. The Oxford researchers said that all those enrolled would be completely fit, well and recovered from their first Covid infection.
Participants who develop Covid symptoms will be treated with an antibody drug from Regeneron Pharmaceuticals Inc. that’s been authorised by US regulators, Oxford said. Subjects will only be discharged from quarantine when they are no longer infected and not at risk of infecting others.
While Covid-19 infections have been rare, recent research suggests prior infection may not fully protect young people against reinfection.
The observational study involving US Marine Corps members mostly aged 18 to 20, published in The Lancet, showed that between May and November 2020, about 10 per cent of participants who had previously caught coronavirus became reinfected.
People under 65 who had previously caught coronavirus had 80 per cent protection against reinfection over a six-month window.
Researchers found elderly people were more likely to be infected again, reinforcing the need for vaccine prioritisation.
