Controversial ‘human challenge’ trials for COVID-19 vaccines gain support

Sciences COVID-19 reporting is supported by the Pulitzer Center and the Heising-Simons Foundation.

Since the early days of the pandemic, some researchers have advocated a fast way to determine whether a COVID-19 vaccine works: Intentionally attempt to infect vaccinated volunteers with the virus, SARS-CoV-2. Ethicists and vaccine scientists alike raised red flags, and the discussion has remained mostly theoretical. But now two key elements are taking shape: a large corps of volunteers willing to take part in a “human challenge” trial, and the well-understood lab-grown virus strains needed for the studies.

The volunteers come from an advocacy group, 1Day Sooner, that has signed up more than 30,000 people from 140 countries. The group, co-founded by a 22-year-old, organized an open letter that was signed by 15 Nobel laureates and 100 other prominent researchers, ethicists, and philosophers, which it sent to U.S. National Institutes of Health Director Francis Collins on 15 July. The letter urged the U.S. government “to undertake immediate preparations for human challenge trials” in young, healthy people, who are less likely to suffer severe disease from COVID-19. Among the signatories was Adrian Hill of the University of Oxford, whose lab developed one of the leading COVID-19 vaccine candidates and plans to produce virus strains that could be used in the trials.

Researchers use human challenges to test vaccines for other diseases, including cholera and malaria, but in those experiments, proven drugs can help “rescue” study participants if the vaccine doesn’t work and they become seriously ill. In a June report on COVID-19 vaccine challenges, an advisory group to the World Health Organization (WHO) was split over whether they should take place in the absence of a rescue treatment. The group was also evenly divided on whether human challenges would truly speed the vaccine effort, given that efficacy trials using participants at risk of natural infection have already begun. Still, the report offered guidelines for these trials, suggesting they should recruit volunteers between ages 18 and 25 and require them to remain in “high-level isolation units” during the study so they don’t infect others.

Sophie Rose, 22, says she is ready to take part. She co-founded 1DaySooner with Josh Morrison, a Harvard Law School graduate who, in 2014, helped start Waitlist Zero, an advocacy group for kidney donations. Rose earned her bachelor’s degree in biology from Stanford University in 2019 and that December moved to the University of Oxford to work on cancer research, hoping to tour Europe during breaks. Because of COVID-19, she has not yet had the chance to leave Oxford. “It’s been a weird, weird turn of events,” says Rose, who plans to study epidemiology at Johns Hopkins University’s Bloomberg School of Public Health in the fall.

Morrison was thinking of starting an advocacy group when he came upon an unpublished literature review about COVID-19 human challenge studies that Rose had co-authored. He invited her to join the nascent effort. “She immediately stood out as a star in our early, informal group working on what would become 1Day Sooner,” says Morrison, who is 35 and too old to take part in a human challenge study himself. “Sophie was someone who was young enough to represent the challenge volunteer perspective, but knowledgeable enough to hold her own in any conversation with experts.”

“This is definitely not a space that I thought I would end up in,” says Rose, now the director of research for the group. “Advocacy is not my area. I much prefer to lean into the research side.”

1Day Sooner “is playing a major role in showing that there are young people willing to take risks for the greater good,” says Stanley Plotkin, a veteran vaccine researcher who has played a leading role in pushing forward the SARS-CoV-2 human challenge model.

Rose says she decided she would put her body on the line because of “logistical reasoning” and data. A 6 July paper she and Morrison co-authored with their team and academic researchers in Clinical Infectious Diseases explored ways human challenge studies might speed the search for a safe and effective COVID-19 vaccine, such as revealing whether a vaccine candidate elicits the immune responses that correlate with protection.

The challenge trials will require large amounts of strains of SARS-CoV-2 that are grown in a biosafety level 3 laboratory under strict “good manufacturing practices.” Based on how readily the strains infect tissue cultures, developers can carefully calibrate the doses. Hill’s lab at Oxford—which is formally collaborating with 1Day Sooner—and Curative Inc., a biotech startup in Los Angeles that makes diagnostics for the disease, have both agreed to make the challenge strains. “A number of people were pretty frustrated that no one was working on this,” says Fred Turner, a 25-year-old who co-founded Curative 6 months ago.

Making the challenge virus will likely take at least until September, Turner says. At that point, according to the WHO proposal, trials should recruit volunteers to test three different doses to find one that causes mild respiratory illness in 70% of people. WHO estimates it will take 2 months after viral strains are made and characterized to launch a challenge study.

Even if human challenge trials can’t be started until late fall, they could still answer key questions about how well a potential vaccine works, Rose says. And if conventional trials have failed to identify a good candidate by then, challenge trials could help triage the more than 150 COVID-19 vaccines being developed. Enthusiasm for the human challenge model could also grow if a rescue treatment becomes available.

“If the last 6 months have taught us nothing else, the progression of this entire thing has been fairly uncertain,” Rose says. “There is a world in which we have a vaccine by then and that would be great, but there’s also a world in which we don’t. I know I would much rather live in a world where we were ready to implement a human challenge study.”

 

https://www.sciencemag.org/news/2020/07/controversial-human-challenge-trials-covid-19-vaccines-gain-support