Pandemic influenza vaccine (H1N1)(GlaxoSmithKline Biologicals SA)

After the initial identification of the H1N1 pandemic influenza strain in Mexico in April 2009 and its subsequent global spread, several monovalent influenza vaccines were developed as part of the pandemic response. Three of these vaccines, Pandemrix, Arepanrix and Focetria were adjuvanted. One of these, the AS03-adjuvanted Pandemrix vaccine, was primarily used in Europe. Following widespread Pandemrix vaccine administration in Scandinavia, an increased risk of narcolepsy was noted in observational studies. Subsequently, this increased risk was also reported in other European countries as well. In contrast, studies from Canada of a similar AS03-adjuvanted vaccine, Arepanrix, did not demonstrate a similar increased risk of narcolepsy. No studies have identified an increased risk of narcolepsy following the MF59-adjuvanted Focetria vaccine. For many potential pandemic influenza strains, adjuvants might be required to solicit a protective immune response. Thus, it is critical that we understand the nature of the association between adjuvanted vaccine receipt and narcolepsy. Here, we present a potential hypothesis for narcolepsy seen during the 2009 H1N1 pandemic in AS03-adjuvanted influenza vaccine recipients.

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.