Ebola Vaccine Trials Carry Risks for Companies in Chase
Each of the Ebola vaccines being
lined up for testing carries potential downsides, researchers
say, ranging from efficacy that faded in less than a year to the
chance it will give healthy people flu-like symptoms.
Human trials, just starting on some vaccines, could also
unveil unknown side effects, an unwelcome possibility for shots
designed to be taken by people who may never be infected with
Ebola. That’s why it’s imperative to cast a wide net in seeking
a solution, said Matthias Schnell, a microbiologist at Thomas
Jefferson University in Philadelphia.
“We really should test as many vaccines as we can,”
Schnell, who is working on a vaccine that targets Ebola and
rabies, said in a telephone interview. “We need way more
clinical data for each vaccine before we go ahead with mass
vaccination.”
Safety testing has already begun on vaccines from
GlaxoSmithKline Plc (GSK), which is working with the U.S. National
Institutes of Health, and NewLink Genetics Corp. (NLNK), which is
testing a product developed by government researchers in Canada.
The next step, efficacy trials in humans, could start next year
for Glaxo’s product in affected regions in Africa.
Meanwhile, clinical trials could begin later next year for
as many as three other vaccines. While the vaccines have shown
some levels of effectiveness in animals, that’s no guarantee
they’ll work as well when they are tested in humans, said Thomas
Geisbert, a virologist at the University of Texas Medical Branch
in Galveston, Texas.
U.S. Navy microbiologist Lt. Jimmy Regeimbal handles a vaccine box with blood samples... Read More
Arsenal of Alternatives
“That’s why it’s good to have an arsenal,” Geisbert said
by telephone. “So that if one doesn’t work, you will have
plenty of alternatives.”
Vaccines work by stimulating the body to generate
antibodies with the ability to remember the virus. That allows
them to recognize Ebola once an infection takes place, and mount
a rapid counterattack. They differ from ZMapp and other
experimental medicines given to Ebola patients primarily because
the vaccines are designed for healthy people as a way to keep
them from becoming infected.
The Glaxo and NewLink vaccines “have both been shown to be
effective in monkeys, so there’s every reason to think they’ll
be effective,” said Kartik Chandran, a microbiologist at the
Albert Einstein College of Medicine in New York. “But you can’t
assume the same thing will hold true in humans. There have been
nasty surprises before.”
Modified Viruses
The vaccines from Glaxo and NewLink are based on modified
viruses that are changed so they express an Ebola protein that’s
strong enough to stimulate an immune response, but doesn’t carry
the part of the Ebola virus that makes people sick. Glaxo’s
vaccine is based on a chimpanzee cold virus, while the NewLink
vaccine is based on vesicular stomatitis virus, which is found
in cows.
For London-based Glaxo’s vaccine, there are unanswered
questions about whether it will be able to protect against Ebola
for an extended length of time, Schnell said.
A study in monkeys, published last month in the journal
Nature Medicine, showed efficacy of the single-dose version of
the vaccine waning over several months. While one dose of the
vaccine protected all of the monkeys given the vaccine from a
lethal dose of Ebola after five weeks, it only protects about
half of the animals after 10 months.
Giving the monkeys a booster shot of a different vaccine
construct provided longer-lasting protection, but Glaxo isn’t
using that version in its initial studies in humans.
‘Effective Response’
Even with the one-dose version “we are hoping this vaccine
will effectively prime the immune system so that when it does
see a small amount of virus” the body will be able to mount an
effective response, said Ripley Ballou, a Glaxo vice president.
Johnson & Johnson (JNJ), meanwhile, plans to test a vaccine it
developed with a planned booster shot. The company’s human trial
is set to begin in March 2015. While giving everyone two shots
rather than one adds a logistical challenge, J&J thinks it could
be the best way to provide long-term protection.
It “has the potential to provide the durability needed to
ensure complete protection against the disease, particularly
when we don’t how long an Ebola outbreak will continue,” said
Seema Kumar, a J&J spokeswoman.
Durability, though, remains a key question for Ebola
vaccines, according to Geisbert. In Africa, if patients have to
keep coming in for booster shots, “it could be a very big
problem,” he said. “You are lucky to get someone to come in
one time, not multiple times.”
Vaccines based on weakened, live viruses that can still
replicate “tend to have more durability,” said Geisbert. But
they may also cause flu-like symptoms in some cases, he said.
“If you get high fever after you get vaccinated, that
would be the end of the vaccine,” Schnell said.
NewLink Vaccine
NewLink’s vaccine is one with a weakened live virus that
can still replicate. The Ames, Iowa-based company has started or
will soon begin first-stage clinical trials in the U.S., Canada,
Switzerland, Germany, and two African nations, Chief Executive
Officer Charles Link said in an Oct. 14 interview.
Healthy volunteers in the trial will receive the vaccine,
and then be tracked to see how their body responds, Link said.
The first participants will get a very low dose of the vaccine
to make sure it is safe before the dosage is gradually escalated
for later subjects, Link said by telephone.
“We’re doing everything in our power to get the vaccine
moving forward and get it into the hot zone,” he said.
NewLink’s Chief Financial Officer John Henneman declined to
comment on potential side effects.
While researchers often look at how well vaccines do in
stimulating the production of antibodies, that isn’t always the
best predictor, said Ben Neuman, a virologist at the University
of Reading in the U.K. For example, he said, vaccines for HIV
have triggered a good antibody response yet failed in human
testing.
“Ebola is good at hiding,” Neuman said in a telephone
interview. Making a vaccine “is hard,” he added. “If it was
easy we would have one by now.”
To contact the reporters on this story:
Robert Langreth in New York at
rlangreth@bloomberg.net;
Shannon Pettypiece in New York at
spettypiece@bloomberg.net;
Caroline Chen in New York at
cchen509@bloomberg.net
To contact the editors responsible for this story:
Reg Gale at
rgale5@bloomberg.net
Andrew Pollack
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