The
vaccine safety surveillance system effectively detected a very rare adverse event,
narcolepsy, in subjects receiving AS03-adjuvanted A(H1N1) pandemic
vaccine made using the European inactivation/purification protocol. The reports of increased cases of
narcolepsy in non-vaccinated subjects infected with wild A(H1N1) pandemic influenza virus suggest a role for the
viral antigen(s) in disease development. However, additional investigations are needed to better understand what factor(s) in wild
influenza infection trigger(s)
narcolepsy in susceptible hosts. An estimated 31 million doses of European AS03-adjuvanted A(H1N1) pandemic
vaccine were used in more than 47 countries. The Canadian AS03-adjuvanted A(H1N1) pandemic
vaccine was used with high coverage in Canada where an estimated 12 million doses were administered. As no similar
narcolepsy association has been reported to date with the AS03-adjuvanted A(H1N1) pandemic
vaccine made using the Canadian inactivation/purification protocol, this suggests that the
AS03 adjuvant alone may not be responsible for the
narcolepsy association. To date, no
narcolepsy association has been reported with the MF59®-adjuvanted A(H1N1) pandemic
vaccine. This review article provides a brief background on
narcolepsy, outlines the different types of
vaccine preparations including the ones for
influenza, reviews the accumulated evidence for the safety of adjuvants, and explores the association between
autoimmune diseases and natural
infections. It concludes by assimilating the historical observations and recent clinical studies to formulate a feasible hypothesis on why
vaccine-associated
narcolepsy may not be solely linked to the
AS03 adjuvant but more likely be linked to how the specific
influenza antigen component of the European AS03-adjuvanted pandemic
vaccine was prepared. Careful and long-term epidemiological studies of subjects who developed
narcolepsy in association with AS03-adjuvanted A(H1N1) pandemic
vaccine prepared with the European inactivation/purification protocol are needed.