COVID-19: New UK Challenge Trial to Investigate Reinfection

Peter Russell

April 19, 2021

Recruitment has begun for a human challenge trial to investigate what kind of immune response can prevent people from developing COVID-19 for a second time.

Prof Helen McShane/SMC

Researchers at the University of Oxford will re-expose participants to SARS-CoV-2 to see how the immune system reacts a second time round.

The trial will be led by Helen McShane, professor of vaccinology at the university's Department of Paediatrics.

She told a briefing, hosted by the Science Media Centre: "If we can determine the level of protection, or the level of immune response, above which an individual cannot be infected, then that will help us determine whether the vaccines will be effective, without necessarily having to test them in phase 3 efficacy trials."

Trial in Two Phases

The 12-month study will take place in two phases with different participants in each phase.

The first phase, starting this month, will be a dose escalation study involving 24 healthy participants aged 18 to 30 who have previously been naturally infected with SARS-CoV-2. They will be inoculated with the original strain from Wuhan, China.

It will seek to establish the lowest dose of the virus needed in order for it to begin replicating in around half of the participants, while producing few or no symptoms.

Participants will be quarantined in a hospital suite for a minimum of 17 days under the care of the research team. They will undergo CT scans of the lungs and MRI scans of the heart.

Any participants who develop symptoms will be given medical treatment with the Regeneron monoclonal antibody treatment.

The next part of the study will involve between 10 and 40 volunteers and aim to confirm the dose to be used in subsequent studies.

"In phase 2, we will explore two different things," said Prof McShane. "First, we will define very carefully the baseline immune response in the volunteers, before we infect them. We will then infect them with the dose of virus chosen from the first study and measure how much virus we can detect after infection.

"We will then be able to understand what kind of immune responses protect against reinfection. Second, we will measure the immune response at several time points after infection so we can understand what immune response is generated by the virus."

Prof McShane said she hoped the trial would provide answers about correlates of protection. "If we find that [in] volunteers who have above a certain level of, for example, antibody response, it is not possible to reinfect them, then we have a correlate of protection. That will help us with vaccine development, [and] that will enable us, potentially, to licence new vaccines, on the basis of that correlate."

'Larger Questions Can Be Addressed'

In February this year, the UK became the first country in the world to approve a COVID-19 human challenge trial in which healthy young people could be exposed to SARS-CoV-2 for the first time to increase understanding of how the virus affects people.

Prof Chris Chiu, clinical reader and honorary consultant in infectious diseases at Imperial College London, and chief investigator of that study, said: "We are very pleased that the Oxford study, on which we are collaborating closely, is to go ahead.  

"By bringing together the findings from our initial SARS-CoV-2 human challenge study in people who have previously not had COVID-19 with those from this study, larger and more broad-ranging questions can be addressed. 

"In particular, we will define how re-infection differs from a first infection with this virus, which may have important implications for how the pandemic is managed going forward as more people develop immunity."

Lawrence Young, a virologist and professor of molecular oncology at the University of Warwick, said: "An important aspect will be determining how long protection from symptomatic infection lasts after natural infection and what aspects of immunity are responsible for this protection."


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