Global Clinical Sciences, Vaccines Research, Novartis Vaccines Srl, via, Fiorentina 1, Siena 53100, Italy.
Harvard Medical School, Division of Rheumatology, Brigham and Women's, Hospital, 45 Francis Street, Boston, MA 02115, USA.
J Autoimmun. 2014 May;50:1-11. doi: 10.1016/j.jaut.2014.01.033. Epub 2014 Feb 19.
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.
疫苗安全监测系统有效地检测到了一种非常罕见的不良事件，即接受使用欧洲失活/纯化方案制备的 AS03 佐剂 A(H1N1)大流行性流感疫苗的受试者中出现的发作性睡病。非接种疫苗但感染野生 A(H1N1)大流行性流感病毒的受试者中发作性睡病病例增加的报告表明，病毒抗原在疾病发展中起作用。但是，需要进一步研究以更好地了解野生流感感染中的哪些因素会引发易感宿主的发作性睡病。估计有 3100 万剂欧洲 AS03 佐剂 A(H1N1)大流行性流感疫苗在 47 个以上国家使用。加拿大 AS03 佐剂 A(H1N1)大流行性流感疫苗在加拿大广泛使用，估计接种了 1200 万剂。由于迄今为止，没有报告称使用加拿大失活/纯化方案制备的 AS03 佐剂 A(H1N1)大流行性流感疫苗与发作性睡病有关，这表明 AS03 佐剂本身可能不是发作性睡病的原因。迄今为止，未报告使用 MF59®佐剂 A(H1N1)大流行性流感疫苗与发作性睡病有关。本文简要介绍了发作性睡病，概述了不同类型的疫苗制剂，包括流感疫苗，综述了佐剂安全性方面的累积证据，并探讨了自身免疫性疾病与自然感染之间的关系。本文最后综合了历史观察和最近的临床研究结果，提出了一个可行的假设，即疫苗相关性发作性睡病可能不仅仅与 AS03 佐剂有关，而更可能与欧洲 AS03 佐剂大流行性流感疫苗中特定的流感抗原成分的制备方式有关。需要对接受使用欧洲失活/纯化方案制备的 AS03 佐剂 A(H1N1)大流行性流感疫苗后发生发作性睡病的受试者进行仔细和长期的流行病学研究。
