Swine flu jab and narcolepsy may be linked by autoimmune response
Vaccine may have caused narcolepsy by triggering the production of antibodies which destroy a sleep-regulating part of the brain, a new study suggests
Scientists appear close to pinpointing why a swine flu vaccine given to six million people in Britain triggered the devastating sleep disorder, narcolepsy, in rare cases.
The Pandemrix vaccine, made by GlaxoSmithKline (GSK), and which was recommended by the UK government to high-risk groups during the 2009-10 swine flu pandemic, was withdrawn after medical records showed a spike in the number of cases of narcolepsy presenting in doctors’ surgeries.
But until now it has not been clear why the jab caused the chronic illness, which involves uncontrollable daytime sleepiness, in around one in 55,000 recipients.
The latest study suggests that in rare cases, Pandemrix led to patients producing antibodies that attacked and destroyed a critical hub of brain cells that help regulate tiredness.
Dr Sohail Ahmed, global head of clinical sciences at Novartis Vaccines and first author of the study, said: “There’s a lot of evidence now to suggest that narcolepsy is an autoimmune disease. In our study, we found antibodies that could cross-react to both the flu protein produced by the vaccine and receptors on the neurons.”
The study, published in the journal Science Translational Medicine, suggests that shortly after having the vaccine, the patients affected would have lost most of a group of 70,000 neurons that are responsible for producing the “wakefulness” hormone, hypocretin.
As a result, they developed narcolepsy, which is characterised by overwhelming daytime sleepiness.
The condition is permanent and sleep attacks can strike dozens of times a day at random – even mid-conversation. Some people also experience night terrors and a condition called cataplexy, where muscle control disappears after a sudden burst of emotion such as surprise or happiness, leading to a person slumping or collapsing on the spot.
The condition can be controlled somewhat with a combination of powerful sleeping drugs at night and stimulants, such as Modafinil, during the day.
Although the government in the UK acknowledges the link between Pandemrix and narcolepsy, they have rejected the compensation claims of about 80 people on the grounds that their disabilities are not “severe”.
Last month, compensation for the patients became more likely, however, after a tribunal ordered the government to pay £120,000 in damages to a 12-year-old boy, after finding that narcolepsy had changed his life severely and permanently.
In the latest work, the researchers started by trawling databases for brain proteins that might resemble those in the vaccine. The search turned up a suspect, showing that part of the receptor for hypocretin closely resembles part of the H1N1 swine flu virus.
“It was a really exciting moment,” said Lawrence Steinman, a professor of paediatrics and of neurology at Stanford University and the paper’s senior author.
The scientists found that the virus protein was present in much higher levels in the Pandemrix vaccine than another swine flu vaccine, used at the time, that has not been linked to narcolepsy. The exact form of the protein was also slightly different.
The scientists then obtained blood samples from 20 patients who had developed narcolepsy after being given Pandemrix and six people who had been immunised with the other vaccine, called Focetria.
They found that 17 of the 20 narcolepsy patients had antibodies that reacted to both flu virus proteins produced by the vaccine and to the hypocretin receptor, suggesting that their immune system had confused the two targets. None of the six people in the control group had “cross-reacting” antibodies.
In a statement, GSK said it was closely reviewing the findings. “Patient safety is GSK’s number one priority and we are actively conducting research into the observed association between Pandemrix and narcolepsy and the interaction this vaccine might have had with other risk factors in those affected,” the company said.
“We’re also continuing to support ongoing work from other experts and organisations investigating reported cases of this condition and we hope these efforts will enable us to provide more answers in the future. We take the safety of patients who entrust their health in our vaccines and medicines very seriously.”