Pandemic influenza vaccine (H1N1)(GlaxoSmithKline Biologicals SA)

To investigate a potential risk for multiple sclerosis (MS) after vaccination with Arepanrix, the GlaxoSmithKline AS03-adjuvanted influenza A(H1N1)pdm09 vaccine, we used the provincewide immunization registry for Manitoba, Canada, to match 341,347 persons vaccinated during the 2009 pandemic to 485,941 unvaccinated persons on age, sex, address, and a propensity score measuring the probability of vaccination. We used a previously validated algorithm to identify MS cases from provincial hospital, physician, and prescription drug claims databases. After 12 months of follow-up, the age-adjusted incidence rate of MS was 17.7 cases per 100,000 person-years in the Arepanrix cohort and 24.2 per 100,000 in the unvaccinated cohort. The corresponding adjusted hazard ratio was 0.9. We observed similar patterns when we measured incidence over the entire follow-up period. The AS03 adjuvant, a candidate for inclusion in future pandemic vaccines, does not appear to increase the short-term risk for MS when included in influenza vaccines.

We previously reported an increased frequency of antibodies to hypocretin (HCRT) receptor 2 in sera obtained from narcoleptic patients who received the European AS03-adjuvanted vaccine Pandemrix (GlaxoSmithKline Biologicals, s.a.) for the global influenza A H1N1 pandemic in 2009 [A(H1N1)pdm09]. These antibodies cross-reacted with a particular fragment of influenza nucleoprotein (NP) - one of the proteins naturally contained in the virus used to make seasonal influenza vaccine and pandemic influenza vaccines. The purpose of this commentary is to provide additional insights and interpretations of the findings and share additional data not presented in the original paper to help the reader appreciate the key messages of that publication. First, a brief background to narcolepsy and vaccine-induced narcolepsy will be provided. Then, additional insights and clarification will be provided on the following topics: 1) the critical difference identified in the adjuvanted A(H1N1)pdm09 vaccines, 2) the contributing factor likely for the discordant association of narcolepsy between the AS03-adjuvanted pandemic vaccines Pandemrix and Arepanrix (GlaxoSmithKline Biologicals, s.a.), 3) the significance of detecting HCRT receptor 2 (HCRTr2) antibodies in some Finnish control subjects, 4) the approach used for the detection of HCRTr2 antibodies in vaccine-associated narcolepsy, and 5) the plausibility of the proposed mechanism involving HCRTr2 modulation in vaccine-associated narcolepsy.