[Ip-health] New York Times: Ebola Vaccine, Ready for Test, Sat on the Shelf

Thiru Balasubramaniam thiru at keionline.org
Thu Oct 23 23:57:01 PDT 2014


http://www.nytimes.com/2014/10/24/health/without-lucrative-market-potential-ebola-vaccine-was-shelved-for-years.html
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HEALTH | NYT NOW
Ebola Vaccine, Ready for Test, Sat on the Shelf
By DENISE GRADY OCT. 23, 2014

GALVESTON, Tex. — Almost a decade ago, scientists from Canada and the
United States reported that they had created a vaccine that was 100 percent
effective in protecting monkeys against the Ebola virus. The results were
published in a respected journal, and health officials called them exciting.
The researchers said tests in people might start within two years, and a
product could potentially be ready for licensing by 2010 or 2011.

It never happened. The vaccine sat on a shelf. Only now is it undergoing
the most basic safety tests in humans — with nearly 5,000 people dead from
Ebola and an epidemic raging out of control in West Africa.

Its development stalled in part because Ebola is rare, and until now,
outbreaks had infected only a few hundred people at a time. But experts also
acknowledge that the absence of follow-up on such a promising candidate
reflects a broader failure to produce medicines and vaccines for diseases
that
afflict poor countries. Most drug companies have resisted spending the
enormous sums needed to develop products useful mostly to countries with
little ability to pay.

Now, as the growing epidemic devastates West Africa and is seen as a
potential threat to other regions as well, governments and aid groups have
begun to open their wallets. A flurry of research to test drugs and
vaccines is
underway, with studies starting for several candidates, including the
vaccine
produced nearly a decade ago.

A federal official said in an interview on Thursday that two large studies
involving thousands of patients were planned to begin soon in West Africa,
and were expected to be described in detail on Friday by the World Health
Organization.

With no vaccines or proven drugs available, the stepped-up efforts are a
desperate measure to stop a disease that has defied traditional means of
containing it.

“There’s never been a big market for Ebola vaccines,” said Thomas W.
Geisbert, an Ebola expert here at the University of Texas Medical Branch in
Galveston, and one of the developers of the vaccine that worked so well in
monkeys. “So big pharma, who are they going to sell it to?” Dr. Geisbert
added: “It takes a crisis sometimes to get people talking. ‘O.K. We’ve got
to
do something here.’ ”

Dr. James E. Crowe Jr., the director of a vaccine research center at
Vanderbilt University, said that academic researchers who developed a
prototype drug or vaccine that worked in animals often encountered a
“biotech valley of death” in which no drug company would help them cross
the finish line.

To that point, the research may have cost a few million dollars, but tests
in humans and scaling up production can cost hundreds of millions, and
bringing a new vaccine all the way to market typically costs $1 billion to
$1.5
billion, Dr. Crowe said. “Who’s going to pay for that?” he asked. “People
invest in order to get money back.”

The Ebola vaccine on which Dr. Geisbert collaborated is made from
another virus, V.S.V., for vesicular stomatitis virus, which causes a mouth
disease in cattle but rarely infects people. It had been used successfully
in
making other vaccines.

The researchers altered V.S.V. by removing one of its genes — rendering
the virus harmless — and inserting a gene from Ebola. The transplanted
gene forces V.S.V. to sprout Ebola proteins on its surface. The proteins
cannot cause illness, but they provoke an immune response that in monkeys,
considered a good surrogate for humans, fought off the disease.

The vaccine was actually produced in Winnipeg, Manitoba, by the
Public Health Agency of Canada. The Canadian government patented it, and
800 to 1,000 vials of the vaccine were produced. In 2010, it licensed the
vaccine, known as VSV-EBOV, to NewLink Genetics in Ames, Iowa.

The Canadian government donated the existing vials to the World
Health Organization, and safety tests of the vaccine in healthy volunteers
have begun.

NewLink’s product is one of two leading vaccines being tested. The
other, which uses a cold virus that infects chimpanzees, was developed by
researchers at the National Institutes of Health and GlaxoSmithKline. The
first tests of an earlier version of it, employing a different cold virus,
began
in 2003.

Several other vaccine candidates, not as far along, are also in the
pipeline and may be ready for safety testing next year. Once any drugs or
treatments pass the safety tests, they will be available for use in larger
numbers of people, and health officials are grappling with whether they
should be tested for efficacy in the traditional way, in which some people
at
risk are given placebos instead of the active drug.

Governments and the military became interested in making vaccines
against Ebola and a related virus, Marburg, during the 1990s after a Soviet
defector said the Russians had found a way to weaponize Marburg and load
it into warheads. Concerns intensified in 2001 after the Sept. 11 terrorist
attacks and anthrax mailings.

“The National Institutes of Health came up with a program called
Partnerships in Biodefense that partnered researchers like me with
companies, usually small companies,” Dr. Geisbert said.

The government money led to major advances in the laboratory, Dr.Geisbert
said, but was insufficient to cover the huge costs of human trials. Nor
could the small companies that were involved in the early studies in
animals afford to pay for human trials. No finished product came to market.

Dr. Geisbert moved on, working on treatments for Ebola and another
version of the V.S.V. vaccine. For the vaccine work, his main collaborator
has been Dr. Heinz Feldmann, the chief of virology at the Rocky Mountain
Laboratories in Hamilton, Mont., part of the National Institute of Allergy
and Infectious Diseases.

The newer version of the vaccine uses a slightly different form of V.S.V.,
one that Dr. Geisbert said he thought might be less likely to cause side
effects, and more likely to gain quick approval because it has been used as
the basis for an H.I.V. vaccine and is known to the Food and Drug
Administration. But the new version, VesiculoVax, made by Profectus
Biosciences in Baltimore, has not yet been tested in humans.

The V.S.V. products are live vaccines, with replicating viruses that may
cause a reaction. It is not clear what level of side effects will be
considered
acceptable.

Chills and nausea are possible, Dr. Geisbert said, but he added, “Who
cares, if you survive Ebola?”

Most vaccines are given to prevent disease before people are exposed to
it, and the plan is to use Ebola vaccines that way. But the V.S.V. vaccines
have also been shown to protect monkeys even after the animals have been
exposed to a heavy dose of Ebola — if given soon after exposure.

Researchers hope that they will work that way for people, too. If they
do, health workers and family members who have been in contact with a
patient might be protected, instead of having to spend 21 days of dread,
waiting to see if they get sick.

Dr. Geisbert spends much of his time working with Ebola and other
deadly viruses in a Biosafety Level 4 laboratory at the Galveston National
Laboratory, where the researchers wear spacesuits that each come with an
independent air supply, and visiting journalists are required not to report
which floor the labs are on.

This month, one of his tasks is to test the Profectus vaccine and an
experimental treatment against the Ebola strain that is causing the current
epidemic. The virus is from a species called Ebola Zaire, against which the
products have already been shown to work. But different strains within a
species can vary genetically by 2 percent to 7 percent, Dr. Geisbert said.

Most of the time, those small variations do not matter, and a drug or
treatment that works against one strain will work against all. But once in
a while, the difference matters.

“We don’t know for 100 percent certainty until we prove it in animals,”
Dr. Geisbert said. “The companies I work with are smart. They want that
answer sooner rather than later, before they go investing millions of
dollars
to put this into humans.”


Andrew Pollack contributed reporting from Los Angeles.
A version of this article appears in print on October 24, 2014, on page A



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