In mid-February, it was confirmed that a selection of up to 90 young, healthy volunteers, unlikely to develop serious illness, would be deliberately infected with COVID-19 in a UK study1. This will be the world’s first study of this type for COVID-19, and has been under consideration since the pandemic began.
The UK has ostensibly done nothing by halves during the last year – hit overwhelmingly hard by cases, pressure on the National Health Service, and, tragically, lost lives, it is now seemingly the poster child for rapid vaccination roll-out. As of February 20th 2021, almost 17 million2 people have received the first dose of a coronavirus vaccine in the United Kingdom.
The UK government appears determined to remain at the forefront; this challenge study has already received £33.6 million3 in investment.
In the first stage – known as the virus characterisation study4 – researchers will investigate the required viral load to cause infection in this group (using the ‘original’ strain that has been circulating in the UK since March 2020). Following this, a small number of volunteers will be given vaccine candidates proven safe in clinical trials, and then exposed to COVID-19, with the aim of identifying the most effective vaccines and accelerating their development.
The history of challenge trials
The first challenge trial is perhaps the best known5, as a staple of school biology syllabuses. In 1796, Edward Jenner created the earliest version of a smallpox vaccine by taking a sample from a cowpox sore and putting it into the skin of his gardener’s eight-year-old son. He then deliberately exposed the child to smallpox, but he did not become infected. Not likely that this would be ethically acceptable today!
Jenner went on to test the method in over 6,000 people – and 200 years later, smallpox vaccines allowed for the eradication of the disease in the global population.
During the 20th and 21st centuries, challenge trials have been conducted in influenza, cholera and malaria, among others. They have also been under consideration for the Zika virus that emerged as a major health crisis in Brazil and other South American and Caribbean countries in 2015.
Why conduct challenge trials?
Challenge trials are not a required element of every vaccination development program. However, there are a number of factors that may make conducting such a study desirable for a specific disease6:
- Animal models are imprecise in reflecting human disease caused by the infection
- The disease has an acute onset, and can be readily and objectively detected
- There are existing effective treatments that can be administered at an appropriate time to prevent significant illness, and prevent risk of death
- There is a significant time imperative to develop understanding of the disease and vaccines/treatments for it – clearly the case with COVID-19
There will inevitably be questions as to the requirement for such trials for COVID-19:
- Why would anybody agree to be deliberately infected with a virus that, as yet, has no effective rescue therapy?
- Do we need to take the risks when we now have a number of approved vaccines being rolled out?
- Whilst young people may be at the lowest risk of serious illness and death, some people suffer with debilitating symptoms for many months (‘long-COVID’), which may not be reversible
- Considering the current lack of full understanding of COVID-19, how does this challenge trial sit with the medical principle of ‘do no harm’?
- If a participant becomes seriously ill, will significant damage be done to public trust in science at a critical time, when vaccine hesitancy is already prevalent in some communities?
Human challenge trials are not new, and hold promise in building our knowledge of COVID-19. However, the ethical implications are many, and must be carefully considered.