Ebola vaccine clinical trials in U.S. full of volunteers

The risk of contracting Ebola virus in suburban Washington, D.C., is vanishingly low. In fact, with the recovery and Friday's release from hospital there of Dallas nurse Nina Pham, it is actually nil.

But that fact isn't deterring people from stepping forward to volunteer for one of 78 spots in two clinical trials of an experimental Ebola vaccine designed by scientists at the National Microbiology Laboratory in Winnipeg.

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The clinical trials are being conducted in Bethesda, Md., a science hub that is home to the U.S. National Institutes of Health and the Walter Reed Army Institute of Research, the two facilities doing the research.

Ninety minutes drive away, straight up highway 270, is the U.S. Army Medical Research Institute on Infectious Diseases, where one of the strains of Ebola Ebola Reston was first identified in monkeys imported from the Philippines. Scientists at USAMRIID, as it is known, collaborated with the Winnipeg lab in the making of the Canadian vaccine.

In other words, this is a nexus of the high calibre research, with many laboratories devoted to work on very bad bugs. And scientists in the labs who study Ebola and its cousin, the Marburg virus, have waited a long time for a chance to be vaccinated against the deadly viruses they research.

Healthy adults over 18

"We're not short of volunteers," says Col. Shon Remich, director of translational medicine at Walter Reed and an associate investigator on one of the trials.

We're not short of volunteers.A lot of people want to be part of the solution.-Col.ShonRemich, Walter Reed Army Institute of Research

"A lot of people want to be part of the solution," says Remich, who acknowledges he wishes he could volunteer to take the vaccine.

That's not to say researchers are the only volunteers for the trials, or that volunteers are only being drawn from the research community. Organizers of the trials are looking for healthy adults 18 to 65 for the NIH trial, 18 to 50 at Walter Reed.

They want a mix of men and women, but are excluding pregnant women and medical professionals currently caring for patients. People who work with animals, take care of children under five or live with anyone who has a suppressed immune system are not eligible for the NIH trial.

Those exclusions are because the vaccine contains live virus though not, of course, Ebola virus. This vaccine cannot give a recipient Ebola disease.

Still, there is some possibility recipients will emit or "shed" the viruses the vaccine does contain. The researchers are being cautious. This is, after all, the first time this vaccine has been tested in people.

The vaccine, which the Canadian government licensed to NewLink Genetics of Ames, Iowa, is called VSV-ZEBOV. The VSV part of the name is short for vesicular stomatitis virus, a live animal virus that is harmless to humans.

It has been genetically modified so that it produces a protein made by Ebola viruses, in this case the Zaire strain of Ebola which is the one responsible for the West African outbreak. That's the Z (Zaire) EBOV (Ebola virus) part of the name.

Introducing that protein to recipients' immune systems should trigger the production of antibodies which would then mount up to fight off Ebola Zaire, if the recipient ever encounters it. Encountering it, though, is not part of these studies. While challenge studies are used for some mild pathogens vaccinated volunteers are exposed to a pathogen to see if the vaccine works that would never be done with something as dangerous as Ebola.

Antibodies

In these studies, the researchers will look for antibodies to the Ebola protein in blood drawn from the volunteers and will watch to see if antibody levels rise over time.

Volunteers will get either the vaccine or an injection of a placebo, probably saline. The primary goal is to see if people can safely take this vaccine. So far, some of the people who have received injections have experienced low grade fevers and muscle aches the type of reaction one often sees in people who get vaccinated for anything. They are actually signs the vaccine is working.

Both trials are starting with low doses and are working their way up to higher doses only after it is determined if low doses are tolerable. That approach is called a "safety stagger," says Remich. A safety review committee will assess the first dose results before the trial organizers can move up to the next dose.

"The protocol is written to be cautious, so there is a step-wise enrolment," explains Dr. John Beigel, an associate investigator on the NIH trial.

"The last thing you want to do is vaccinate 50 people all in one day and then find that it's really toxic."

One of the challenges with a new vaccine or drug is determining what constitutes a dose. How much is needed to get the desired effect? How little can you give, so you can minimize the risk of side-effects while still getting a protective effect?

"We're trying to find that sweet spot in the middle where we generate antibodies but the side-effects are tolerable," Beigel explains.

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The Walter Reed study is testing what happens when recipients receive only one dose of the vaccine, which many including the scientist who led the development program hope will be sufficient for this vaccine. A one-dose vaccine is much easier to administer, especially in emergency circumstances, than a two-dose vaccine, especially if the doses have to be given several weeks apart.

Two doses

The NIH study is looking at a two-dose regimen, trying to see if two low doses given 28 days apart would be as effective as a single dose that contains more vaccine than the two combined. It would be a way to stretch scarce vaccine, Beigel says.

Each study has three arms, which will receive a low, intermediate or high dose (or two) of vaccine. In the NIH trial, the intermediate dose is seven times larger than the low dose, and the high dose is five times higher than the intermediate. In the Walter Reed study, the intermediate and high doses involve 10 times more vaccine than the dose below.

In both trials, 10 people each will receive the low, intermediate and high doses, and nine people will receive placebo. Neither the researchers nor the recipients will know until after the results have been calculated who got which.

Both hope to have some data on the safety of the vaccine and information that can be used to make a decision about the size of a dose in December, though the results of the analysis of the impact of the second dose in the NIH study aren't expected until January, Beigel says.

The Walter Reed trial will follow volunteers for 180 days, drawing blood at sporadic intervals over that time. The NIH trial will follow its volunteers for a year to try to get a picture of how long the Ebola antibodies stick around.

Additional safety trials of the VSV-ZEBOV vaccine will soon start in Germany, Switzerland, Gabon and Kenya. The World Health Organization said Friday that much larger trials aimed at seeing if the vaccine is protective could start in December or shortly thereafter, depending on the safety trials results.