Research ArticleInfluenza

Antibodies to influenza nucleoprotein cross-react with human hypocretin receptor 2

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Science Translational Medicine  01 Jul 2015:
Vol. 7, Issue 294, pp. 294ra105
DOI: 10.1126/scitranslmed.aab2354

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  • RE: Ahmed et al, Sci. Transl. Med. 7, 294ra105 (2015)
    • Robbert van der Most, GSK Vaccines
    • Other Contributors:
      • Sofia Maria Buonocore, GSK Vaccines
      • Bruce Innis, GSK Vaccines

    In their recent publication in Science Translational Medicine, Ahmed et al. proposed that the increased risk of narcolepsy following vaccination with Pandemrix™ could potentially be explained by antibody cross-reactivity between the H1N1 influenza virus nucleoprotein (NP) and the human hypocretin receptor 2 (HCRT-R2) (1). Subsequent comments in Science (2) and Science Translational Medicine (3) discussed the relevance of these findings in explaining any potential links between vaccination, influenza and narcolepsy.

    The starting point for Ahmed and colleagues was the observation that very few cases of narcolepsy were reported after vaccination with Focetria™ thus prompting a search for sequence differences between the re-assortant vaccine strains used to produce Pandemrix and Focetria (seed virus strains X-179A and X-181, respectively). Where differences between X-181 and X-179A sequences were found, they searched for sequence homologies between these influenza virus sequences, and the sequences of hypocretin and hypocretin receptors 1 and 2. The bio-informatic analysis was then based on the premise that a single amino acid difference existed at position 116 of the nucleoprotein (NP) sequences in the re-assortant strains for Pandemrix and Focetria, X-179A (I) and X-181 (M), respectively. This analysis resulted in the identification of amino acid similarity between the influenza A(H1N1)pdm09 virus nucleoprotein (NP) (YDKEEIRRIWR, defined as the mimicry sequence) and...

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    Competing Interests: All authors are employees of the GSK group of companies. Robbert van der Most and Bruce Innis own shares in GSK and are listed as inventors on patents owned by GSK

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