By Rich Haridy, October 20, 2020
The first stage of the trial will be infecting healthy volunteers with the virus to discover the lowest dose that consistently leads to the development of COVID-19
Researchers in the United Kingdom are set to undertake controversial human challenge trials to accelerate the testing of COVID-19 vaccines. The trials, planned to commence in January 2021, will initially begin by deliberately infecting young and healthy volunteers with the SARS-CoV-2 virus to investigate how low doses of the virus lead to acute disease.
Vaccines generally take a long time to produce. Aside from all the clinical work that goes into the development of a vaccine, real-world human trials are slow. First, a candidate vaccine must to be tested for safety in small groups, and then larger cohorts are recruited to test for efficacy.
Just this final efficacy phase of vaccine trials often takes over a year. Thousands of subjects are recruited, randomized into either placebo or vaccine groups, and then followed for months. Researchers then compare the amount of infections between the vaccine and placebo groups to determine what real-world efficacy the vaccine has protecting a person from infection.
One way to speed up this process is by conducting what are called “human challenge studies.” These trials involve testing a vaccine by deliberately exposing volunteers to a virus. These kinds of trials are ethical minefields, requiring expansive knowledge of individual viruses in order to minimize risk to healthy volunteers.
And while calls for COVID-19 challenge trials began almost as soon as the pandemic kicked off early in 2020, it has taken months to better understand exactly how this novel coronavirus behaves in humans. Now, authorities in the UK say they are ready for challenge trials to commence in January 2021.
Called the Human Challenge Programme, the project is a large partnership between Imperial College London, the UK National Health Service, and hVIVO – an organization that has conducted human challenge studies for over 30 years. The UK Government will initially invest £33.6 million (USD $43.5 million) in the project.
The first phase of the project is called a virus characterization study. This phase involves exposing young and healthy volunteers to very low doses of SARS-CoV-2. The goal of this initial phase is to find the lowest dose of virus that can consistently lead to COVID-19 in most subjects.
This phase will take place in an isolated research unit at London’s Royal Free Hospital. Up to 90 subjects will be recruited, aged between 18 and 30.
This virus characterization phase is expected to run until May 2021. After that point, once the effects of the virus have been evaluated and an appropriate dose has been established, vaccine efficacy trials will commence.
The exact details of the actual vaccine challenge trials have yet to be determined. So it is unclear exactly which vaccines will be tested, and what kind of protocol will be used to test them.
Chris Chiu, lead researcher on the upcoming challenge studies, suggests the project will move cautiously and with appropriate oversight from regulatory bodies to ensure volunteers are as safe as possible.
“Our number one priority is the safety of the volunteers,” explains Chiu, from Imperial College London. “My team has been safely running human challenge studies with other respiratory viruses for over 10 years. No study is completely risk free, but the Human Challenge Programme partners will be working hard to ensure we make the risks as low as we possibly can.”
Experts not directly affiliated with the Human Challenge Programme have welcomed the UK government’s move, however, many suggest ethical concerns do need to be carefully managed. Katharine Wright, from the Nuffield Council on Bioethics, cites informed consent as perhaps one of the most important aspects of these kinds of trials.
“There are significant challenges in ensuring volunteers thoroughly understand the risks of what they are being asked to do, and the uncertainty of any benefit,” says Wright. “The implications are significant as volunteers will be committing to stay within a biosecure facility until they are no longer infectious.”
Julian Tang, from the University of Leicester, points out that ethical issues are certainly being managed in regards to COVID-19 challenge trials. However, he does add these kinds of trials can sometimes be of limited value as they only evaluate vaccine response in the youngest, healthiest populations.
“…perhaps the main limitation is that the challenge studies can ethically only select healthy adult volunteers – not children or the elderly, or those vulnerable groups with diabetes, hypertension, chronic heart, lung, kidney disease, or pregnant women or immunocompromised people – so the interpretation of such studies will, ironically, be only applicable to those who least need the protection,” notes Tang.
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