Human-Challenge Trials – Should we deliberately infect volunteers with Covid-19 to test a vaccine?

Content originally from Medical Research Council

The UK has been a world-leader in vaccine research ever since Edward Jenner first introduced the term vaccine. What may surprise you is that Jenner’s iconic experiment performed in 1796 of deliberately infecting a boy with cowpox, and then subsequently infecting him with smallpox could be considered one of the first human-challenge trials. Today, deliberately infecting human volunteers in a controlled clinical setting is used to develop new vaccines for a range of different diseases, including malaria, influenza and typhoid to name just a few. Indeed, MRC has supported human-challenge trials for over 70 years, the earliest being at our Common Cold unit, where coronaviruses were identified as a cause of the common cold.

Dr Martin Broadstock

Recent reports of the potential use of human-challenge trials to tackle Covid-19 have brought this approach to vaccine development into the spotlight. Young, healthy volunteers could be injected with an experimental vaccine and then deliberately infected with SARS-CoV-2, the type of coronavirus which causes Covid-19. So, what are the arguments for and against this approach?

Those in support argue that this could significantly fast track the journey to an effective vaccine. The normal trial process for a vaccine takes 5-10 years and costs millions of pounds. Human-challenge trials are smaller than traditional vaccine trials and performed in highly controlled clinics, offering results more quickly and in fewer people. Results can be used to compare many different types of vaccine candidates against each other, speeding up the process from the lab bench to the doctor’s surgery and helping to find the most effective vaccine. This could help save lives. A recent publication suggests that a vaccine could be approved one month faster, preventing an additional 1.1 million infections and an additional 8,000 deaths in the US alone, if human-challenge trials were set up quickly[1].

However, these types of trials are not without risk. Usually, they are used for diseases which have existing cures or are self-limiting (i.e. a condition which will either resolve on its own or has no long-term harmful effects on a person’s health). The World Health Organisation has published a series of eight ethical criteria for the use of SARS-CoV-2 human-challenge trials. These include: a strong scientific justification, the overall benefits of the study should outweigh the risk, close public engagement, close coordination with regulators, be performed where there are good facilities, minimize the risk to the participants, be reviewed by specialist independent committee and involve rigorous informed consent[2].

Following these criteria, it may be possible to conduct human-challenge trials in younger participants, who are less likely to have serious disease. Risks can also be reduced by using the lowest possible dose of the virus that leads to infection whilst minimising symptoms. As with all human-challenge trials, informed consent is a critical issue, and existing study designs have many methods available to ensure that people understand what they are signing up for. This will be particularly important for studies using SARS-CoV-2 where we do not yet understand who will develop serious symptoms and may need hospitalisation or who will remain relatively symptom free. Crucially, there’s still a lot we don’t know about “long-Covid” – the longer-term health consequences that may follow infection.

Whilst these discussions on the use of human-challenge trials are ongoing, the worldwide research community has not stopped using traditional studies to try and develop an effective vaccine for SARS-CoV-2. There are currently hundreds of vaccines undergoing testing around the world, with many already in the final stages of clinical evaluation. It could be that these bear fruit sooner rather than later.

Our understanding of the human immune system and ways to combat disease have come a long way since Jenner’s time. The commitment and dedication from across the sector to finding a workable vaccine is resolute and our community is looking at every tool at its disposal to find a solution.

[1] https://www.medrxiv.org/content/10.1101/2020.09.15.20195495v1

[2] https://apps.who.int/iris/bitstream/handle/10665/331976/WHO-2019-nCoV-Ethics_criteria-2020.1-eng.pdf?ua=1