A group of scientists including three Nobel laureates in medicine has
proposed that U.S. health officials chart a new path to developing Ebola
drugs and vaccines by harnessing antibodies produced by survivors of
the deadly outbreak.
The proposal builds on the use of “convalescent serum,” or survivors’
blood, which has been given to at least four U.S. Ebola patients who
then recovered from the virus. It is based on an approach called passive
immunization, which has been used since the 19th century to treat
diseases such as diphtheria but has been largely surpassed by
vaccination.
The scientists propose using new genetic and other technologies to find
hundreds or thousands of different Ebola antibodies, determine their
genetic recipe, grow them in commercial quantities and combine them into
a single treatment analogous to the multi-drug cocktails that treat
HIV-AIDS.
That contrasts with current drug development, which focuses on finding
one molecule, or a small number, to defeat the Ebola virus that has
killed nearly 5,000 people in West Africa and infected thousands more
since March.
Nobel laureates David Baltimore, an expert in the molecular biology of
the immune system, James Watson, co-discoverer of the double helix that
is DNA, and Jim Simons, who founded hedge-fund Renaissance Technologies
and was a pioneer in the quant revolution on Wall Street, are among the
advocates of the idea. It was outlined in a letter that was reviewed by
Reuters.
The proposal was sent to officials at the Department of Health and
Human Services, including the Food and Drug Administration, to lawmakers
and to biotech companies. They have not responded, said geneticist
Michael Wigler of Cold Spring Harbor Lab, who wrote and gathered
signatures for the position paper. The recipients did not respond to
Reuters’ requests for comment or said they had no comment.
The scientists urged government leadership without offering a specific
development or production plan, and it is not clear whether the idea
would offer a faster track to success than current efforts.
“Government agencies, commercial manufacturers and perhaps
philanthropy” must work together to form a research and development
infrastructure capable of producing therapeutic antibodies, Wigler said
in an interview.
Although there is no proof that blood from survivors helps Ebola
patients survive, it is known that patients recover when their own blood
produces enough antibodies to stop the virus.
OLD PROCESS
Antibodies are proteins produced by the immune system to fight
bacteria, viruses, and other invaders, from colds to measles. Giving
antibodies to infected people would offer their immune systems a head
start in fighting Ebola, the theory goes.
If the antibodies in survivors’ blood is genetically sequenced, they
would provide a recipe for treatments, which could be produced with
technologies already used to manufacture antibodies that target cancer
or rheumatoid arthritis, the scientists said.
“It would cost less than $1 million to get the genetic sequences of the
antibodies from people who have recovered, and then we would have an
armamentarium of hundreds or even thousands of antibodies,” Wigler said.
He speculated that the idea has not gained traction before because
“academics are trained to overlook the obvious.” The approach would be
difficult, and “many people in this day and age are afraid to risk
failure,” he said.
Ebola experts were cautious about the possibility that hundreds of anti-Ebola antibodies would prevent or cure infections.
Studies have shown that some antibodies that neutralize Ebola virus in
test tubes don’t protect infected lab animals, said Dr. Thomas Geisbert
of the University of Texas Medical Branch, who is working on Ebola
vaccines. He also questioned whether the proposal would save time, given
the need to test any antibody cocktail in both lab animals and human
volunteers.
One of the most promising experimental treatments, Mapp
Biopharmaceutical’s ZMapp, consists of three different antibodies
produced by mice infected with Ebola. Initial research was published in
2000, but it took until this summer for a study to show that ZMapp cured
Ebola-infected lab monkeys.
GlaxoSmithKline Plc (GSK.L) and Johnson & Johnson (JNJ.N) are among
the drugmakers working on an Ebola vaccine. Both declined to comment on
whether the antibodies proposal might be effective against Ebola.
Wigler acknowledges that none of those who have signed on to the
proposal are experts on Ebola. Nor do they know how long it might take
to develop a production line, get regulatory approval, and test the
antibodies.
LESSON FROM DIPHTHERIA
European researchers separately are planning to test whether Ebola
survivors’ serum can cure patients, starting this month. But relying on
transfusions of survivors’ blood for those antibodies is a daunting task
in West Africa, given the need to screen it for other diseases and
ensure health workers aren’t exposed during the collection or infusion
process.
By contrast, “it takes a very short time” to produce countless copies
of antibody genes, said molecular biologist Michel Nussenzweig of the
Rockefeller University, an expert on the immune system who was not
involved in the Ebola proposal. “Hundreds are not a problem; this has
been automated,” he said. However, he questioned whether hundreds would
be necessary to fight Ebola.
Wigler’s answer: the Ebola virus is mutating. That might thwart an
three-antibody cocktail like ZMapp, he said, but it is highly unlikely
that the targets of hundreds of antibodies would all mutate. A diversity
of antibodies “mimics the body’s own defenses and could overcome
mutations in the virus that may develop,” he said.
Multiple antibodies is what finally worked against HIV, which causes AIDS and, like the Ebola virus, mutates rapidly.
“We should make sure we learn from HIV to take our best shot at Ebola,” Nobelist Baltimore said in an interview.
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