Earlier challenge trials deliberately infected

volunteers with flu virus and other pathogens.

approve, scientists could infect the first vol-

unteers in January 2021. The first studies,
involving up to 100 volunteers ages 18 to 30,
would identify the lowest viral dose needed
to cause an infection. Then they could move
forward with head-to-head comparisons of
different vaccine candidates. Although the
experiment won’t replace traditional efficacy
trials, it could highlight which vaccines war-
rant further investment, Chiu says.
Chiu is comfortable with intentionally
infecting people with SARS-CoV-2 because
there is growing evidence that young adults
have a low risk of serious illness. He con-
sulted with researchers at King’s College
London who help manage an app tracking
COVID-19 COVID-19 symptoms for more than 4 mil-

Downloaded from http://science.sciencemag.org/ on December 5, 2020

lion people. Among 650 young adults with

New challenges emerge for confirmed cases, 90% had no symptoms after
3 weeks, and the symptoms of a few “outliers”
resolved after a few months, Chiu says.

planned human challenge trials In the United States, however, the en-
couraging recent vaccine results have put a
damper on human challenge trials. A month
Scientists debate risks and benefits of intentionally ago, virologist Matthew Memoli put the final
exposing volunteers to dangerous virus touches on plans for a challenge trial at the
National Institute of Allergy and Infectious
Diseases (NIAID). But Anthony Fauci, head
By Warren Cornwall cal concerns. For example, because there are of NIAID, and Francis Collins, head of the Na-
no reliable treatments for severe COVID-19, tional Institutes of Health, recently suggested

I
n the early days of the COVID-19 pan-
demic, tens of thousands of young volun-
teers offered to risk their health by letting
scientists intentionally infect them with
the pandemic coronavirus, hoping to
speed the hunt for a vaccine or treatment.
Several research groups announced plans to
run these so-called human challenge trials,
even as some scientists questioned whether
they could be conducted ethically.
Now, with recent news that conventional
human trials have produced several promis-
ing vaccines, scientists are debating whether
planned challenge trials are still needed. In
the United States, one nascent effort is on
hold. In the United Kingdom, however, re-
searchers say they are moving ahead. “There
are still many strong arguments for pursu-
ing” challenge trials, says immunologist
Christopher Chiu of Imperial College Lon-
don, leader of the proposed U.K. trial.
In traditional human trials, researchers
people who volunteer to test a vaccine could the experiment is no longer necessary.
die if they get sick. So, medical authorities That’s welcome news to some, who fear
around the world have adopted a cautious that challenge trials present serious risks to
approach. Even 1 year after the outbreak be- volunteers. Others, however, say the apparent
gan, no such trial is underway. Meanwhile, success of some vaccines could strengthen
11 vaccines have entered the final phase of the case for challenge trials. Once viable vac-
conventional human testing, with cines are available, it’s harder to
promising results already emerg- justify continuing with traditional
ing: Four vaccines have shown up Science’s trials, in which thousands of people
to 95% efficacy (see p. 1151). COVID-19 are given a placebo while others are
Proponents say challenge experi- reporting is vaccinated, says bioethicist Nir Eyal
supported by the
ments could still advance science of Rutgers University, New Bruns-
Pulitzer Center
and save lives. They could be used and the wick. “Are you going to hope that
to compare the effectiveness of dif- Heising-Simons tens of thousands of people will
ferent vaccines, for instance, and Foundation. altruistically be willing to forgo ac-
help quickly screen the most prom- cess to a proven vaccine?” he asks.
ising second-generation candidates from the Seema Shah, a bioethicist at Northwest-
dozens now in the works. Challenge studies ern University, thinks human challenge trials
could also help answer unknowns, such as could still be useful, but there is less urgency
whether vaccines block infection entirely or now. And she would like to see more ways
simply prevent people from getting sick. to ensure participants’ safety, such as find-
It’s hard to use large trials to determine ing biological markers for people at greater
PHOTO: AP PHOTO/CHARLES DHARAPAK

give volunteers either a vaccine or a placebo,
then wait months or longer for enough cases
to emerge to gather statistically rigorous re-
sults. Challenge trials can move faster by first
vaccinating volunteers and then intentionally
exposing them to SARS-CoV-2 in a controlled
setting. Researchers would then closely mon-
itor the volunteers for days or weeks.
But challenge trials are also rife with ethi-
whether a vaccinated person still sheds the
virus, says epidemiologist Marc Lipsitch
of Harvard University. “It’s almost pro-
hibitively expensive because in a 30,000-
person trial you have to test 30,000 people
a week,” he says.
The initiative Chiu heads, the Human
Challenge Consortium, is backed by £33 mil-
lion from the U.K. government. If regulators
risk of getting sick. “I think I would feel more
comfortable waiting a bit to see how those
things developed and whether the risk could
be minimized further,” she says.
Lipsitch agrees that “the immediate
need is not great” for human challenge tri-
als. But, he adds, researchers “need to keep
preparing in case we have reason to start
doing them.” j

1150 4 DECEMBER 2020 • VOL 370 ISSUE 6521 sciencemag.org SCIENCE

Published by AAAS
New challenges emerge for planned human challenge trials
Warren Cornwall

Science 370 (6521), 1150.

DOI: 10.1126/science.370.6521.1150

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