Shrinking coronavirus outbreaks may hurt vaccine trials

LONDON — The top teams rushing to develop coronavirus vaccines are alerting governments, health officials and shareholders that they may have a big problem: The outbreaks in their countries may be getting too small to quickly determine whether vaccines work.

A leader of the Oxford University group, one of the furthest ahead with human trials, admits the reality is paradoxical, even “bizarre,” but said the declining numbers of new infections this summer could be one of the big hurdles vaccine developers face in the global race to beat down the virus.

Even as new cases are growing worldwide, transmission rates are falling in Britain, China and many of the hardest-hit regions in the United States — the three countries that have experimental vaccines ready to move into large-scale human testing in June, July and August.

The shrinking number of new infections in former hot spots is good news, of course. But vaccine developers need sufficient numbers of infected people, with and without symptoms, circulating in the general population — in the streets, workplaces, clinics — to test whether the vaccine protects volunteers when they are exposed.

Adrian Hill, director of the Jenner Institute at Oxford, told the Sunday Telegraph newspaper that his team was in “a race against the virus disappearing.”

Hill, who is a co-leader of the Oxford effort, said, “We’re in the bizarre position of wanting COVID to stay, at least for a little while. But cases are declining.”

In the United States, the Trump administration has pledged to pursue a vaccine at “warp speed,” plugging the possibility of having something ready by the end of the year. That would be an unprecedented feat, as vaccines in the past have taken years or decades to bring to market.

Getting approval for use in the United States will require largescale trials conducted over several months — long enough for researchers to observe whether people randomly assigned to receive the experimental vaccine are getting sick significantly less often than people who get a placebo.

Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said the trials will involve 30,000 volunteers, and, to assess how well a vaccine is working, scientists will need to see at least 100 of those volunteers get sick. If there’s not much virus around, hitting that target might be tough.

“I hope — I don’t want to see a lot of infections in the United States. I wouldn’t want people to get infected and suffer and die,” Fauci said.

Researchers may have to get creative to find the outbreaks they need.

Britain has the highest coronavirus death toll in Europe, but new infections here are rapidly tapering off. Dr. John McCauley, director of the Worldwide Influenza Centre at the Francis Crick Institute in London, imagined that healthy volunteers left to wander London might not encounter many infected individuals. The capital has been reporting several hundred new cases a day, but that’s in a city of almost 9 million.

And so the Oxford trial is focusing its volunteer recruitment effort on British health care workers, “as they have the highest rates of virus infections,” said Sarah Gilbert, a leader of the group.

If case infections continue to decline, the Oxford scientists are also looking beyond Britain and Europe for trial sites. They got approval last week from the health regulator of Brazil, where the virus continues to surge, to conduct a trial there involving 2,000 volunteers.

Fauci said sites in Brazil and South Africa may be considered for U.S.-led trials.

“I think you’re going to have to go with where the dynamics of the outbreak are, and that changes. You really have to be mobile and flexible,” Fauci said.

In China, where at least five groups are developing vaccines, a dwindling number of reported infections has similarly prompted researchers to move ahead with plans to test their vaccines in the Philippines and elsewhere.

But overseas trials can present ethical issues and questions about oversight. It may be harder to get true informed consent from volunteers, especially where literacy is low or translation is required. There’s also debate among ethicists about whether communities where trials were conducted should expect priority access once vaccines have been demonstrated to be safe and effective.

Another option for researchers would be “human challenge trials,” where healthy volunteers are given a vaccine and intentionally “challenged” with the coronavirus. Protocols for such experiments are being written.

Others say it might be worth a try. In an article in the journal Vaccine, Dr. Stanley A. Plotkin of the University of Pennsylvania and Dr. Arthur L. Caplan of New York University wrote that deliberately causing disease in humans “is normally abhorrent, but asking volunteers to take risks without pressure or coercion is not exploitation but benefiting from altruism.”

Then they quoted Shakespeare, who wrote, “Desperate diseases by desperate measures are relieved.”