No serological evidence of influenza A H1N1pdm09 virus infection as a contributing factor in childhood narcolepsy after Pandemrix vaccination campaign in Finland.
BACKGROUND
Narcolepsy cataplexy syndrome, characterised by excessive daytime sleepiness and cataplexy, is strongly associated with a genetic marker, human leukocyte antigen (HLA) DQB1*06:02. A sudden increase in the incidence of childhood narcolepsy was observed after vaccination with AS03-adjuvanted Pandemrix influenza vaccine in Finland at the beginning of 2010. Here, we analysed whether the coinciding influenza A H1N1pdm pandemic contributed, together with the Pandemrix vaccination, to the increased incidence of childhood narcolepsy in 2010. The analysis was based on the presence or absence of antibody response against non-structural protein 1 (NS1) from H1N1pdm09 virus, which was not a component of Pandemrix vaccine.


METHODS
Non-structural (NS) 1 proteins from recombinant influenza A/Udorn/72 (H3N2) and influenza A/Finland/554/09 (H1N1pdm09) viruses were purified and used in Western blot analysis to determine specific antibody responses in human sera. The sera were obtained from 45 patients who fell ill with narcolepsy after vaccination with AS03-adjuvanted Pandemrix at the end of 2009, and from controls.


RESULTS
Based on quantitative Western blot analysis, only two of the 45 (4.4%) Pandemrix-vaccinated narcoleptic patients showed specific antibody response against the NS1 protein from the H1N1pdm09 virus, indicating past infection with the H1N1pdm09 virus. Instead, paired serum samples from patients, who suffered from a laboratory confirmed H1N1pdm09 infection, showed high levels or diagnostic rises (96%) in H1N1pdm virus NS1-specific antibodies and very high cross-reactivity to H3N2 subtype influenza A virus NS1 protein.


CONCLUSIONS
Based on our findings, it is unlikely that H1N1pdm09 virus infection contributed to a sudden increase in the incidence of childhood narcolepsy observed in Finland in 2010 after AS03-adjuvanted Pandemrix vaccination.
Department of Infectious Disease Surveillance and Control, National Institute for Health and Welfare, Helsinki, Finland. krister.melen@thl.fi
Krister
K
Melén
Markku
M
Partinen
Janne
J
Tynell
Maarit
M
Sillanpää
Sari-Leena
SL
Himanen
Outi
O
Saarenpää-Heikkilä
Christer
C
Hublin
Päivi
P
Olsen
Jorma
J
Ilonen
Hanna
H
Nohynek
Ritva
R
Syrjänen
Terhi
T
Kilpi
Arja
A
Vuorela
Turkka
T
Kirjavainen
Outi
O
Vaarala
Ilkka
I
Julkunen
D000293:Adolescent; D000917:Antibody Formation; D002648:Child; D002675:Child, Preschool; D005387:Finland / Q000453:epidemiology; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology; D007252:Influenza Vaccines / Q000009:adverse effects* / Q000627:therapeutic use*; D007251:Influenza, Human / Q000150:complications* / Q000453:epidemiology / Q000276:immunology* / Q000517:prevention & control; D009290:Narcolepsy / Q000209:etiology*; D058873:Pandemics; D012698:Serologic Tests; D017361:Viral Nonstructural Proteins / Q000276:immunology
D007252:Influenza Vaccines; D017361:Viral Nonstructural Proteins; C556153:pandemrix