As Ebola outbreak calms down, University of Minnesota must wait to test vaccines

University of Minnesota researchers overseeing a major drug trial in West Africa are having to play catch-up with the Ebola virus, which emerged there last year, killed thousands of people — and then retreated before researchers could test two experimental vaccines against it.

Plans to inject 28,000 people with one of two experimental vaccines — or a placebo — have been suspended in Liberia because the country that once was the epicenter of the deadly Ebola outbreak is reporting no new infections.

If the virus isn't circulating, the trial is pointless because there is no way to know if experimental vaccines are protecting people, said James Neaton, a U biostatistics professor and a global authority on running clinical trials.

"What you want to know is … are there more cases of Ebola among the people who received placebo vs. those who received the vaccine?" he said. "That's the true test. Once you've got that data, then you feel comfortable giving [the vaccine] to millions of people."

The Minnesota researchers were invited late last year by the National Institutes of Health to provide data analysis and leadership on the vaccine study because of their experience running trials of treatments for HIV and other disorders in Africa.

Neaton and colleagues already have participated since February in safety testing of the vaccines on more than 1,000 people in Liberia, and since March in a clinical trial of experimental treatments for patients who are sick with Ebola. In May, they also will start a monitoring trial of as many as 2,000 Ebola survivors in Liberia to see if they develop medical complications over time.

But hopes have been pinned on the so-called PREVAIL trial and others like it to produce the world's first Ebola vaccines and prove they are safe and effective.

"We must move forward … so that ultimately we can determine whether these experimental vaccines can protect against Ebola virus disease and therefore be used in future Ebola outbreaks," said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, in a March press statement.

The slowdown caused by the absence of Ebola disrupted what has been one of the fastest vaccine developments in medical history. Neaton said his team was ready to begin the Phase 1 clinical trial of the vaccine's safety in Liberia in February, even as manufacturers still were determining the appropriate dosages.

"Once the world recognized this was a major problem last summer," Neaton said, "the vaccine manufacturers really accelerated their research."

One vaccine in the trial is cAd3-EBOZ, developed by federal researchers and GlaxoSmithKline, and the other is VSV-ZEBOV, developed by Canadian health authorities and licensed to Merck. The vaccines use genetically modified variations of other viruses to provoke the immune system to respond against Ebola.

Now, one option is to move the trial north to Guinea, where Ebola still seems to be circulating. Beyond gaining the cooperation of that nation's government, the switch would require re-creating the intricate system created in Liberia for dispensing vaccine, said Cavan Reilly, a U associate biostatistics professor who just returned from Liberia.

The Ebola outbreak raised particular concern in Minnesota, which is home to a large Liberian immigrant population. No local cases have been reported, despite Health Department monitoring of 566 travelers from West Africa.

Only four cases of Ebola have been diagnosed in the U.S. — a Liberian who died at a Texas hospital, two nurses who treated him, and a New York doctor who returned from an aid mission in Guinea.

The race for a vaccine has been punctuated by Ebola's fatality rate. In Africa, 41 percent of the suspected and confirmed infections proved fatal.

Health officials believe the death rate from an outbreak would be lower in the U.S., given the wealth of medical resources available. Among seven people brought from Africa to designated U.S. hospitals for treatment, only one died, and his condition was dire upon arrival.

Success in tamping down the outbreak shouldn't result in complacency over vaccine development, Neaton said. A safe vaccine would be a welcome alternative to costly and intrusive measures to identify infected people and prevent them from spreading the virus.