Narcolepsy and A(H1N1)pdm09 vaccination

Abstract

Epidemiological data from several European countries suggested an increased risk of the chronic sleep disorder narcolepsy following vaccination with Pandemrix^™, an AS03-adjuvanted, pandemic A(H1N1)pdm09 influenza vaccine. Further research to investigate potential associations between Pandemrix™ vaccination, A(H1N1)pdm09 influenza infection and narcolepsy is required. Narcolepsy is most commonly caused by a reduction or absence of hypocretin produced by hypocretin-secreting neurons in the hypothalamus, and is tightly associated with HLA-II DQB1*06:02. Consequently, research focusing on CD4⁺ T-cell responses, building on the hypothesis that for disease development, T cells specific for antigen(s) from hypocretin neurons must be activated or reactivated, is considered essential. Therefore, the following key areas of research can be identified, (1) characterization of hypothetical narcolepsy-specific auto-immune CD4⁺ T cells, (2) mapping epitopes of such T cells, and (3) evaluating potential mechanisms that would enable such cells to gain access to the hypothalamus. Addressing these questions could further our understanding of the potential links between narcolepsy and A(H1N1)pdm09 vaccination and/or infection. Of particular interest is that any evidence of a mimicry-based mechanism could also explain the association between narcolepsy and A(H1N1)pdm09 influenza infection.

Keywords: :

• narcolepsy
• A(H1N1)pdm09 influenza
• pandemic
• vaccine
• Pandemrix
• CD4⁺ T cell
• hypocretin

10.4161/hv.27412

Disclosure of Potential Conflicts of Interest

We declare the following interests: R.V.D.M., M.V.M., E.D., M.W., and E.H. are employees of the GlaxoSmithKline group of companies and own shares in GlaxoSmithKline. R.V.D.M., M.V.M., M.W., and E.H. are listed as inventors of patents owned by GlaxoSmithKline Biologicals SA. Writing assistance was utilized in the production of this manuscript and was funded by GlaxoSmithKline Biologicals SA.

Acknowledgments

The authors would like to thank their colleagues Anne Schuind, Corey Mallett, Isabelle Martin, Vincent Bauchau, Ventzislav Vassilev, Camille Planty, and W Ripley Ballou, as well as Prof. Emmanuel Mignot at the Department of Psychiatry, Stanford University Center for Narcolepsy, Palo Alto, CA, for helpful discussions. Finally, they thank Ellen Oe (XPE Pharma & Science on behalf of GlaxoSmithKline) for writing assistance and Ulrike Krause for publication management.

Trademarks

Pandemrix is a trademark of the GlaxoSmithKline group of companies.

Author Contributions

All authors were involved in the initial discussions leading to the design of the research approaches. R.V.D.M., M.V.M., and E.D. further developed the research objectives based on published data and discussions with experts in the field of narcolepsy research. R.V.D.M. wrote the initial draft of the manuscript and is the guarantor of the article. All authors were involved in the further drafting of the manuscript or revising it critically for important intellectual content. All authors approved the manuscript before it was submitted by the corresponding author, had full access to the information used for the manuscript, and had final responsibility to submit for publication.