Amirah Al Idrus | FierceVaccines | 17 December 2014
Finnish Scientists Identify Link Between GlaxoSmithKline’s Swine Flu Vaccine Pandemrix and Narcolepsy
Of the more than 30 million people in almost 50 countries who have received GlaxoSmithKline’s ($GSK) Pandemrix, close to 800 have developed narcolepsy. And now, for the first time, a team from Finland thinks it knows why.
Comparing Pandemrix with Arepanrix, a vaccine used in Canada with the same adjuvant, the researchers found that Pandemrix had more of one structurally altered viral nucleoprotein–a disparity lead researcher Outi Vaarala attributed to the way the vaccines were prepared.
“The vaccine virus itself has components of the virus. It is also supposed to contain viral protein. There’s nothing extraordinary about that,” she told Yle, Finland’s national broadcasting company. “The difference was that Pandemrix had one viral protein in a different form and there was more of it.”
In February 2011, Finland’s National Institute for Health and Welfare announced a spike in narcolepsy cases and a link between Pandemrix and the sleep disorder. Recipients of the vaccine aged between four and 19 had a “manifold” increased risk of developing narcolepsy during the 8 months following vaccination, as compared with those of the same age group who had foregone the vaccine, said the health agency.
In May 2013, researchers in Finland found that it wasn’t only kids who were susceptible to narcolepsy after getting Pandemrix, but adults, too, though the findings suggested that the risk of developing narcolepsy tapers off with age.
And in September 2013, the U.K. government, which had previously turned down compensation claims for Pandemrix-related narcolepsy, changed its mind 7 months after new evidence came to light. Research published in the British Medical Journal showed an increased risk of narcolepsy in English children who had received Pandemrix.
Plos One | 15 December 2014
Antigenic Differences between AS03 Adjuvanted Influenza A (H1N1) Pandemic Vaccines: Implications for Pandemrix-Associated Narcolepsy Risk
Abstract
Background
Narcolepsy results from immune-mediated destruction of hypocretin secreting neurons in hypothalamus, however the triggers and disease mechanisms are poorly understood. Vaccine-attributable risk of narcolepsy reported so far with the AS03 adjuvanted H1N1 vaccination Pandemrix has been manifold compared to the AS03 adjuvanted Arepanrix, which contained differently produced H1N1 viral antigen preparation. Hence, antigenic differences and antibody response to these vaccines were investigated.
Methods and Findings
Increased circulating IgG-antibody levels to Pandemrix H1N1 antigen were found in 47 children with Pandemrix-associated narcolepsy when compared to 57 healthy children vaccinated with Pandemrix. H1N1 antigen of Arepanrix inhibited poorly these antibodies indicating antigenic difference between Arepanrix and Pandemrix. High-resolution gel electrophoresis quantitation and mass spectrometry identification analyses revealed higher amounts of structurally altered viral nucleoprotein (NP) in Pandemrix. Increased antibody levels to hemagglutinin (HA) and NP, particularly to detergent treated NP, was seen in narcolepsy. Higher levels of antibodies to NP were found in children with DQB1*06:02 risk allele and in DQB1*06:02 transgenic mice immunized with Pandemrix when compared to controls.
Conclusions
This work identified 1) higher amounts of structurally altered viral NP in Pandemrix than in Arepanrix, 2) detergent-induced antigenic changes of viral NP, that are recognized by antibodies from children with narcolepsy, and 3) increased antibody response to NP in association of DQB1*06:02 risk allele of narcolepsy. These findings provide a link between Pandemrix and narcolepsy. Although detailed mechanisms of Pandemrix in narcolepsy remain elusive, our results move the focus from adjuvant(s) onto the H1N1 viral proteins.
Click here for the full study and the list of authors.
