The onset of
narcolepsy, an irreversible
sleep disorder, has been associated with 2009
influenza pandemic (pH1N1)
infections in China, and with ASO3-adjuvanted pH1N1 vaccinations using
Pandemrix in Europe. Intriguingly, however, the increased incidence was only observed following vaccination with
Pandemrix but not
Arepanrix in Canada. In this study, the mutational burden of actual
vaccine lots of
Pandemrix (n = 6) and
Arepanrix (n = 5) sourced from Canada, and Northern Europe were characterized by mass spectrometry. The four most abundant
influenza proteins across both
vaccines were
nucleoprotein NP,
hemagglutinin HA, matrix
protein M1, with the exception that
Pandemrix harbored a significantly increased proportion of
neuraminidase NA (7.5%) as compared to
Arepanrix (2.6%). Most significantly, 17 motifs in HA, NP, and M1 harbored mutations, which significantly differed in
Pandemrix versus
Arepanrix. Among these, a 6-fold higher deamidation of HA146 (p.Asn146Asp) in
Arepanrix was found relative to
Pandemrix, while NP257 (p.Thr257Ala) and NP424 (p.Thr424Ile) were increased in
Pandemrix. DQ0602 binding and tetramer analysis with mutated
epitopes were conducted in
Pandemrix-vaccinated cases versus controls but were unremarkable.
Pandemrix harbored lower mutational burden than
Arepanrix, indicating higher similarity to wild-type 2009 pH1N1, which could explain differences in
narcolepsy susceptibility amongst the
vaccines.