The 2009 HINI influenza pandemic left a
troubling legacy in Europe: More than 1300 people who received a vaccine to
prevent the flu developed narcolepsy, an incurable, debilitating condition that
causes overpowering daytime sleepiness, sometimes accompanied by a sudden
muscle weakness in response to strong emotions such as laughter or anger. The
manufacturer, GlaxoSmithKline (GSK), has acknowledged the link, but how the
vaccine might have triggered the condition has been unclear.
In a paper in Science Translational Medicine (STM this week, researchers offer
a possible explanation. They show that the vaccine, caled Pandemrix, triggers
antibodies that can also bind to a receptor in brain cells that help regulate
sleepiness. The work strongly suggests that Pandemrix triggered an autoimmune
reaction that led to narcolepsy in some people who are genetically at risk.
“They put
together quite a convincing picture and provide a plausible explanation for
what has happened," says Pasi Penttinen, who heads the influenza program
at the European Centre for Disease Prevention and Control.“It's really the kind
of work we've been waiting for 5 years." But the results still need to be
confirmed in a larger study, the authors and other narcolepsy researchers say.
A 2013 paper in STM by another group, documenting a difrent type of
vaccine-triggered autoimmune reaction, was retracted after the results proved
irreproducible.
Narcolepsy, a myterious malady that afects roughly one in 3000 people in
Europe, most often appears in childhood or adolescence. Patients lose certain
brain cells in the hypothalamus, leading to a deficiency of hypo-cretin, a
molecule that helps regulate the sleep-wake cycle. Researchers suspect an
autoimmune reaction is to blame because many people who develop narcolepsy-and
just about everyone with the vaccine-associated form-have a specific variant in
a gene in the HLA family, which helps the body distinguish its own proteins
from those made by microbial invaders.
When they heard about the rise in narcolepsy in 2010, neuroscientist Lawrence
Steinman and rheumatologist Sohail Ahmed began scouring databases for proteins
expressed in the brain that might resemble those in the vaccine.
Their search turned up a suspect: a piece of a receptor for hypo-cretin
resembles part of the HIN1 influenza nucleoprotein- which binds to the virus
genome and plays a key role in its replication.The flu vaccine is designed to
trigger antibodies to influenza's surface proteins, but if it elicits
antibodies to the nucleoproteinas well, those might well latch on to the
hypocretin receptor, and eventually lead to death of the cells, the researchers
thought.
In the new work, the researchers added serum from Finnish narcolepsy patients
who had received Pandemrix to cells that were engineered to display human hypo
cretin receptor 2 on their surface. Antibodies from the patients bound to these
cells in 17 of 20 samples. Serum from Italians who had been vaccinated with a
different pandemic vaccine from Novartis, called Focetria, did not have such
antibodies. The researchers also showed that Focetria, which has not been
linked to narcolepsy, had a much lower concentration of nucleoprotein than
Pandemrix did.Approximately, according to the passage, how many people have been vaccinated withPandemrix in Europe?