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Article

Mass Spectrometric Characterization of Narcolepsy-Associated Pandemic 2009 Influenza Vaccines

1
Stanford Center for Sleep Sciences and Medicine, Department of Psychiatry and Behavioral Sciences, Stanford University, 3165 Porter Drive, Stanford, CA 94304, USA
2
Stanford Mass Spectrometry Core, 333 Campus Drive, Mudd 175, Stanford University, Stanford, CA 94305, USA
3
Department of Laboratory Medicine, Karolinska Institutet, 14152 Stockholm, Sweden
*
Author to whom correspondence should be addressed.
Vaccines 2020, 8(4), 630; https://doi.org/10.3390/vaccines8040630
Received: 8 September 2020 / Revised: 21 October 2020 / Accepted: 23 October 2020 / Published: 30 October 2020
(This article belongs to the Special Issue Influenza Virus and Vaccine Development)
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. View Full-Text
Keywords: narcolepsy; influenza vaccine; mass spectrometry; mutations narcolepsy; influenza vaccine; mass spectrometry; mutations
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MDPI and ACS Style

Ambati, A.; Luo, G.; Pradhan, E.; Louis, J.; Lin, L.; Leib, R.D.; Ollila, H.M.; Poiret, T.; Adams, C.; Mignot, E. Mass Spectrometric Characterization of Narcolepsy-Associated Pandemic 2009 Influenza Vaccines. Vaccines 2020, 8, 630. https://doi.org/10.3390/vaccines8040630

AMA Style

Ambati A, Luo G, Pradhan E, Louis J, Lin L, Leib RD, Ollila HM, Poiret T, Adams C, Mignot E. Mass Spectrometric Characterization of Narcolepsy-Associated Pandemic 2009 Influenza Vaccines. Vaccines. 2020; 8(4):630. https://doi.org/10.3390/vaccines8040630

Chicago/Turabian Style

Ambati, Aditya, Guo Luo, Elora Pradhan, Jacob Louis, Ling Lin, Ryan D. Leib, Hanna M. Ollila, Thomas Poiret, Christopher Adams, and Emmanuel Mignot. 2020. "Mass Spectrometric Characterization of Narcolepsy-Associated Pandemic 2009 Influenza Vaccines" Vaccines 8, no. 4: 630. https://doi.org/10.3390/vaccines8040630

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