U.S. Ebola vaccine looks protective but may require high dose: study

TORONTO – A single dose of a U.S.-designed Ebola vaccine may be protective against the disease, a new study suggests. But the research also appears to indicate that dose will have to be relatively large, which may present problems for the vaccine.

The study found that people who got the higher of two doses tested in the trial developed immune responses that look similar to those seen in vaccinated non-human primates who survive exposure to what should have been lethal doses of Ebola. Many of them also developed mild to moderate side-effects.

The vaccine was created by scientists at the U.S. National Institute of Allergy and Infectious Diseases and is being developed by Pharma giant GSK, formerly known as GlaxoSmithKline. The study was published online Wednesday by the New England Journal of Medicine.

Dr. Anthony Fauci, director of the institute, agreed in an interview that the effective dose is “a pretty large” one. But he insisted if that is what it takes for this vaccine to work, that dose size would not be a show stopper.

“We don’t have any problem with the possibility that we might have to use (it),” he said of the higher dose.

It would mean that it will take more of the vaccine to do clinical trials to determine if the vaccine is truly effective, and to vaccinate in West Africa if a decision to do that is made. But that could be done, Fauci said. “They’ll have to make a bit more, but that’s the way it goes.”

He noted another trial of the vaccine, which is still ongoing, is studying a dose that is midway between the two doses this first trial tested. It could be that that dose might work, he said.

GSK also hailed the results.

“We are very encouraged by these positive first trial results showing this type of vaccine has an acceptable safety profile and can produce an immune response against Ebola in humans,” Dr. Moncef Slaoui, the company’s chairman of global vaccines, said in a statement.

Others, though, wondered about the practicality of the size of the effective dose, and about the side-effects seen in people who received the vaccine.

Michael Osterholm, director of the University of Minnesota’s Center for Infectious Diseases Research and Policy, said the amount of vaccine needed to reach the presumed protective response calls into question whether GSK can make enough of the vaccine soon enough to help bring this outbreak under control.

“It’s a front and centre question,” Osterholm said.

The vaccine, called chAd3, is designed to protect against two different Ebola viruses — Ebola Zaire, which is causing the current West African outbreak, and Ebola Sudan. There are five known types of Ebola, but virtually all human disease is caused by Zaire, Sudan and Bundibugyo viruses.

The vaccine cannot infect the recipient with either disease, but it does induce the immune system to respond in ways that should protect if the recipient is later exposed to either strain of Ebola.

The vaccine is one of two which will soon be tested in West Africa in the hopes that they can help to contain the epidemic that has been ravaged Guinea, Sierra Leone and Liberia. New case figures released Wednesday by the World Health Organization set the known cases at just shy of 16,000 and the death toll at 5,689.

The other vaccine, known as rVSV-EBOV, was designed by scientists at the Public Health Agency of Canada’s National Microbiology Laboratory in Winnipeg. The rights to the vaccine were purchased earlier this week by Merck, a major international player in the vaccine market.

There have been concerns that the GSK vaccine would be poorly immunogenic — that it might take two doses to induce a protective response. In the midst of an outbreak — especially one raging in countries with shattered health-care systems — a two-dose regimen is considered far from ideal and perhaps even unworkably complicated.

The Merck vaccine, for which the first trial results are still pending, is expected to generate a stronger immune response at a smaller dose, based on studies in non-human primates. But there have been concerns about it, related to what is known as reactogenicity — the side-effects seen when the vaccine is given.

The vaccine is expected to induce things like headache, malaise, chills and fevers. That constellation of side-effects might seem like a small price to pay for protection against Ebola. But they mirror the early symptoms of Ebola, which could complicate the situation on the ground in affected countries.

One of the surprises of the study of the GSK vaccine is that at the high dose, there were quite a few side-effects reported as well.

“This is sort of what I would have expected to see with the VSV” vaccine, said Dr. Daniel Bausch, an Ebola expert at Tulane School of Public Health and Tropical Medicine in New Orleans.

Osterholm agreed: “From the initial data which is very limited here it raises questions if there would really be any difference between the two.”

Bausch wrote an editorial for the journal which was published with the study. It suggests the world is “one step closer to an Ebola virus vaccine.”

He called the results promising, but noted that scientists do not really know what a protected human immune system looks like; they are extrapolating from what is seen in vaccinated primates.

Bausch also cautioned that results in healthy adults in the United States may not truly reflect how well the vaccine works in people in West Africa. For instance, he noted that studies have shown that some vaccines do not work as well in populations where malaria is omnipresent.

On the plus side, he noted a different formulation of the GSK vaccine currently being tested in Britain — one that protects against only one strain of Ebola, Ebola Zaire — may be more protective than the two-strain version.

Both the GSK and the Merck vaccines are expected to go into trials in West Africa early in the new year.