Antibodies to influenza nucleoprotein cross-react with human hypocretin receptor 2.
Identifieur interne : 000C07 ( Main/Exploration ); précédent : 000C06; suivant : 000C08Antibodies to influenza nucleoprotein cross-react with human hypocretin receptor 2.
Auteurs : Syed Sohail Ahmed [Italie] ; Wayne Volkmuth [États-Unis] ; José Duca [États-Unis] ; Lorenzo Corti [Italie] ; Michele Pallaoro [Italie] ; Alfredo Pezzicoli [Italie] ; Anette Karle [Suisse] ; Fabio Rigat [Italie] ; Rino Rappuoli [Italie] ; Vas Narasimhan [États-Unis] ; Ilkka Julkunen [Finlande] ; Arja Vuorela [Finlande] ; Outi Vaarala [Finlande] ; Hanna Nohynek [Finlande] ; Franco Laghi Pasini [Italie] ; Emanuele Montomoli [Italie] ; Claudia Trombetta [Italie] ; Christopher M. Adams [États-Unis] ; Jonathan Rothbard [États-Unis] ; Lawrence Steinman [États-Unis]Source :
- Science translational medicine [ 1946-6242 ] ; 2015.
Descripteurs français
- KwdFr :
- Alignement de séquences, Anticorps antiviraux (immunologie), Données de séquences moléculaires, Enfant, Grippe humaine (immunologie), Grippe humaine (virologie), Humains, Immunité, Immunoglobuline G (sang), Lignée cellulaire, Narcolepsie (immunologie), Peptides (), Peptides (immunologie), Protéines de liaison à l'ARN (), Protéines de liaison à l'ARN (immunologie), Protéines du core viral (), Protéines du core viral (immunologie), Réactions croisées (immunologie), Récepteurs des orexines (), Récepteurs des orexines (immunologie), Saisons, Spectrométrie de masse, Séquence d'acides aminés, Vaccination, Vaccins antigrippaux (immunologie), Virus recombinants (immunologie).
- MESH :
- immunologie : Anticorps antiviraux, Grippe humaine, Narcolepsie, Peptides, Protéines de liaison à l'ARN, Protéines du core viral, Réactions croisées, Récepteurs des orexines, Vaccins antigrippaux, Virus recombinants.
- sang : Immunoglobuline G.
- virologie : Grippe humaine.
- Alignement de séquences, Données de séquences moléculaires, Enfant, Humains, Immunité, Lignée cellulaire, Peptides, Protéines de liaison à l'ARN, Protéines du core viral, Récepteurs des orexines, Saisons, Spectrométrie de masse, Séquence d'acides aminés, Vaccination.
English descriptors
- KwdEn :
- Amino Acid Sequence, Antibodies, Viral (immunology), Cell Line, Child, Cross Reactions (immunology), Humans, Immunity, Immunoglobulin G (blood), Influenza Vaccines (immunology), Influenza, Human (immunology), Influenza, Human (virology), Mass Spectrometry, Molecular Sequence Data, Narcolepsy (immunology), Orexin Receptors (chemistry), Orexin Receptors (immunology), Peptides (chemistry), Peptides (immunology), RNA-Binding Proteins (chemistry), RNA-Binding Proteins (immunology), Reassortant Viruses (immunology), Seasons, Sequence Alignment, Vaccination, Viral Core Proteins (chemistry), Viral Core Proteins (immunology).
- MESH :
- chemical , blood : Immunoglobulin G.
- chemical , chemistry : Orexin Receptors, Peptides, RNA-Binding Proteins, Viral Core Proteins.
- chemical , immunology : Antibodies, Viral, Influenza Vaccines, Orexin Receptors, Peptides, RNA-Binding Proteins, Viral Core Proteins.
- immunology : Cross Reactions, Influenza, Human, Narcolepsy, Reassortant Viruses.
- virology : Influenza, Human.
- Amino Acid Sequence, Cell Line, Child, Humans, Immunity, Mass Spectrometry, Molecular Sequence Data, Seasons, Sequence Alignment, Vaccination.
Abstract
The sleep disorder narcolepsy is linked to the HLA-DQB1*0602 haplotype and dysregulation of the hypocretin ligand-hypocretin receptor pathway. Narcolepsy was associated with Pandemrix vaccination (an adjuvanted, influenza pandemic vaccine) and also with infection by influenza virus during the 2009 A(H1N1) influenza pandemic. In contrast, very few cases were reported after Focetria vaccination (a differently manufactured adjuvanted influenza pandemic vaccine). We hypothesized that differences between these vaccines (which are derived from inactivated influenza viral proteins) explain the association of narcolepsy with Pandemrix-vaccinated subjects. A mimic peptide was identified from a surface-exposed region of influenza nucleoprotein A that shared protein residues in common with a fragment of the first extracellular domain of hypocretin receptor 2. A significant proportion of sera from HLA-DQB1*0602 haplotype-positive narcoleptic Finnish patients with a history of Pandemrix vaccination (vaccine-associated narcolepsy) contained antibodies to hypocretin receptor 2 compared to sera from nonnarcoleptic individuals with either 2009 A(H1N1) pandemic influenza infection or history of Focetria vaccination. Antibodies from vaccine-associated narcolepsy sera cross-reacted with both influenza nucleoprotein and hypocretin receptor 2, which was demonstrated by competitive binding using 21-mer peptide (containing the identified nucleoprotein mimic) and 55-mer recombinant peptide (first extracellular domain of hypocretin receptor 2) on cell lines expressing human hypocretin receptor 2. Mass spectrometry indicated that relative to Pandemrix, Focetria contained 72.7% less influenza nucleoprotein. In accord, no durable antibody responses to nucleoprotein were detected in sera from Focetria-vaccinated nonnarcoleptic subjects. Thus, differences in vaccine nucleoprotein content and respective immune response may explain the narcolepsy association with Pandemrix.
DOI: 10.1126/scitranslmed.aab2354
PubMed: 26136476
Affiliations:
- Finlande, Italie, Suisse, États-Unis
- Californie, Finlande occidentale, Massachusetts
- Turku
- Université de Turku
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Le document en format XML
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type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Julkunen, Ilkka" sort="Julkunen, Ilkka" uniqKey="Julkunen I" first="Ilkka" last="Julkunen">Ilkka Julkunen</name><affiliation wicri:level="4"><nlm:affiliation>National Institute for Health and Welfare (THL), Helsinki 00300, Finland. Virology, University of Turku, Turku 20520, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>National Institute for Health and Welfare (THL), Helsinki 00300, Finland. Virology, University of Turku, Turku 20520</wicri:regionArea><placeName><settlement type="city">Turku</settlement><region type="région" nuts="2">Finlande occidentale</region></placeName><orgName type="university">Université de Turku</orgName><placeName><settlement type="city">Turku</settlement><region type="région" nuts="2">Finlande occidentale</region></placeName></affiliation></author><author><name sortKey="Vuorela, Arja" sort="Vuorela, Arja" uniqKey="Vuorela A" first="Arja" last="Vuorela">Arja Vuorela</name><affiliation wicri:level="1"><nlm:affiliation>National Institute for Health and Welfare (THL), Helsinki 00300, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>National Institute for Health and Welfare (THL), Helsinki 00300</wicri:regionArea><wicri:noRegion>Helsinki 00300</wicri:noRegion></affiliation></author><author><name sortKey="Vaarala, Outi" sort="Vaarala, Outi" uniqKey="Vaarala O" first="Outi" last="Vaarala">Outi Vaarala</name><affiliation wicri:level="1"><nlm:affiliation>National Institute for Health and Welfare (THL), Helsinki 00300, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>National Institute for Health and Welfare (THL), Helsinki 00300</wicri:regionArea><wicri:noRegion>Helsinki 00300</wicri:noRegion></affiliation></author><author><name sortKey="Nohynek, Hanna" sort="Nohynek, Hanna" uniqKey="Nohynek H" first="Hanna" last="Nohynek">Hanna Nohynek</name><affiliation wicri:level="1"><nlm:affiliation>National Institute for Health and Welfare (THL), Helsinki 00300, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>National Institute for Health and Welfare (THL), Helsinki 00300</wicri:regionArea><wicri:noRegion>Helsinki 00300</wicri:noRegion></affiliation></author><author><name sortKey="Pasini, Franco Laghi" sort="Pasini, Franco Laghi" uniqKey="Pasini F" first="Franco Laghi" last="Pasini">Franco Laghi Pasini</name><affiliation wicri:level="1"><nlm:affiliation>Internal Medicine, Policlinico Santa Maria alle Scotte, Azienda Ospedaliera Universitaria Senese, Siena 53100, Italy. Medical Science, Surgery, and Neuroscience, University of Siena, Siena 53100, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Internal Medicine, Policlinico Santa Maria alle Scotte, Azienda Ospedaliera Universitaria Senese, Siena 53100, Italy. Medical Science, Surgery, and Neuroscience, University of Siena, Siena 53100</wicri:regionArea><wicri:noRegion>Siena 53100</wicri:noRegion></affiliation></author><author><name sortKey="Montomoli, Emanuele" sort="Montomoli, Emanuele" uniqKey="Montomoli E" first="Emanuele" last="Montomoli">Emanuele Montomoli</name><affiliation wicri:level="1"><nlm:affiliation>Molecular and Developmental Medicine, University of Siena, Siena 53100, Italy. VisMederi Srl, Siena 53100, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Molecular and Developmental Medicine, University of Siena, Siena 53100, Italy. VisMederi Srl, Siena 53100</wicri:regionArea><wicri:noRegion>Siena 53100</wicri:noRegion></affiliation></author><author><name sortKey="Trombetta, Claudia" sort="Trombetta, Claudia" uniqKey="Trombetta C" first="Claudia" last="Trombetta">Claudia Trombetta</name><affiliation wicri:level="1"><nlm:affiliation>Molecular and Developmental Medicine, University of Siena, Siena 53100, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Molecular and Developmental Medicine, University of Siena, Siena 53100</wicri:regionArea><wicri:noRegion>Siena 53100</wicri:noRegion></affiliation></author><author><name sortKey="Adams, Christopher M" sort="Adams, Christopher M" uniqKey="Adams C" first="Christopher M" last="Adams">Christopher M. Adams</name><affiliation wicri:level="2"><nlm:affiliation>Stanford University Mass Spectrometry, Stanford University School of Medicine, Palo Alto, CA 94305 USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>Stanford University Mass Spectrometry, Stanford University School of Medicine, Palo Alto</wicri:cityArea></affiliation></author><author><name sortKey="Rothbard, Jonathan" sort="Rothbard, Jonathan" uniqKey="Rothbard J" first="Jonathan" last="Rothbard">Jonathan Rothbard</name><affiliation wicri:level="2"><nlm:affiliation>Immunology, Stanford University School of Medicine, Palo Alto, CA 94305, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Immunology, Stanford University School of Medicine, Palo Alto, CA 94305</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Steinman, Lawrence" sort="Steinman, Lawrence" uniqKey="Steinman L" first="Lawrence" last="Steinman">Lawrence Steinman</name><affiliation wicri:level="2"><nlm:affiliation>Neurology and Neuroscience, Stanford University School of Medicine, Stanford, CA 94305, USA. sohail.q.ahmed@gsk.com steinman@stanford.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Neurology and Neuroscience, Stanford University School of Medicine, Stanford, CA 94305</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2015">2015</date><idno type="RBID">pubmed:26136476</idno><idno type="pmid">26136476</idno><idno type="doi">10.1126/scitranslmed.aab2354</idno><idno type="wicri:Area/PubMed/Corpus">000637</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000637</idno><idno type="wicri:Area/PubMed/Curation">000637</idno><idno 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steinman@stanford.edu.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Global Clinical Sciences, Novartis Vaccines Srl, Siena 53100</wicri:regionArea><wicri:noRegion>Siena 53100</wicri:noRegion></affiliation></author><author><name sortKey="Volkmuth, Wayne" sort="Volkmuth, Wayne" uniqKey="Volkmuth W" first="Wayne" last="Volkmuth">Wayne Volkmuth</name><affiliation wicri:level="2"><nlm:affiliation>Informatics and Information Technology, Atreca Inc., Redwood City, CA 94063, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Informatics and Information Technology, Atreca Inc., Redwood City, CA 94063</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Duca, Jose" sort="Duca, Jose" uniqKey="Duca J" first="José" last="Duca">José Duca</name><affiliation wicri:level="2"><nlm:affiliation>Computer-Aided Drug Discovery, Novartis Institutes for BioMedical Research, Cambridge, MA 02139, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Computer-Aided Drug Discovery, Novartis Institutes for BioMedical Research, Cambridge, MA 02139</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Corti, Lorenzo" sort="Corti, Lorenzo" uniqKey="Corti L" first="Lorenzo" last="Corti">Lorenzo Corti</name><affiliation wicri:level="1"><nlm:affiliation>Formulation Analytics, Novartis Vaccines Srl, Siena 53100, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Formulation Analytics, Novartis Vaccines Srl, Siena 53100</wicri:regionArea><wicri:noRegion>Siena 53100</wicri:noRegion></affiliation></author><author><name sortKey="Pallaoro, Michele" sort="Pallaoro, Michele" uniqKey="Pallaoro M" first="Michele" last="Pallaoro">Michele Pallaoro</name><affiliation wicri:level="1"><nlm:affiliation>Formulation Analytics, Novartis Vaccines Srl, Siena 53100, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Formulation Analytics, Novartis Vaccines Srl, Siena 53100</wicri:regionArea><wicri:noRegion>Siena 53100</wicri:noRegion></affiliation></author><author><name sortKey="Pezzicoli, Alfredo" sort="Pezzicoli, Alfredo" uniqKey="Pezzicoli A" first="Alfredo" last="Pezzicoli">Alfredo Pezzicoli</name><affiliation wicri:level="1"><nlm:affiliation>In Vitro Cell Biology, Novartis Vaccines Srl, Siena 53100, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>In Vitro Cell Biology, Novartis Vaccines Srl, Siena 53100</wicri:regionArea><wicri:noRegion>Siena 53100</wicri:noRegion></affiliation></author><author><name sortKey="Karle, Anette" sort="Karle, Anette" uniqKey="Karle A" first="Anette" last="Karle">Anette Karle</name><affiliation wicri:level="1"><nlm:affiliation>Integrated Biologics Profiling Unit, Novartis Pharma AG, Basel 4057, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Integrated Biologics Profiling Unit, Novartis Pharma AG, Basel 4057</wicri:regionArea><wicri:noRegion>Basel 4057</wicri:noRegion></affiliation></author><author><name sortKey="Rigat, Fabio" sort="Rigat, Fabio" uniqKey="Rigat F" first="Fabio" last="Rigat">Fabio Rigat</name><affiliation wicri:level="1"><nlm:affiliation>Quantitative Sciences, Novartis Vaccines Srl, Siena 53100, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Quantitative Sciences, Novartis Vaccines Srl, Siena 53100</wicri:regionArea><wicri:noRegion>Siena 53100</wicri:noRegion></affiliation></author><author><name sortKey="Rappuoli, Rino" sort="Rappuoli, Rino" uniqKey="Rappuoli R" first="Rino" last="Rappuoli">Rino Rappuoli</name><affiliation wicri:level="1"><nlm:affiliation>Research, Novartis Vaccines Srl, Siena 53100, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Research, Novartis Vaccines Srl, Siena 53100</wicri:regionArea><wicri:noRegion>Siena 53100</wicri:noRegion></affiliation></author><author><name sortKey="Narasimhan, Vas" sort="Narasimhan, Vas" uniqKey="Narasimhan V" first="Vas" last="Narasimhan">Vas Narasimhan</name><affiliation wicri:level="2"><nlm:affiliation>Development, Novartis Vaccines, Cambridge, MA 02139, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Development, Novartis Vaccines, Cambridge, MA 02139</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Julkunen, Ilkka" sort="Julkunen, Ilkka" uniqKey="Julkunen I" first="Ilkka" last="Julkunen">Ilkka Julkunen</name><affiliation wicri:level="4"><nlm:affiliation>National Institute for Health and Welfare (THL), Helsinki 00300, Finland. Virology, University of Turku, Turku 20520, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>National Institute for Health and Welfare (THL), Helsinki 00300, Finland. Virology, University of Turku, Turku 20520</wicri:regionArea><placeName><settlement type="city">Turku</settlement><region type="région" nuts="2">Finlande occidentale</region></placeName><orgName type="university">Université de Turku</orgName><placeName><settlement type="city">Turku</settlement><region type="région" nuts="2">Finlande occidentale</region></placeName></affiliation></author><author><name sortKey="Vuorela, Arja" sort="Vuorela, Arja" uniqKey="Vuorela A" first="Arja" last="Vuorela">Arja Vuorela</name><affiliation wicri:level="1"><nlm:affiliation>National Institute for Health and Welfare (THL), Helsinki 00300, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>National Institute for Health and Welfare (THL), Helsinki 00300</wicri:regionArea><wicri:noRegion>Helsinki 00300</wicri:noRegion></affiliation></author><author><name sortKey="Vaarala, Outi" sort="Vaarala, Outi" uniqKey="Vaarala O" first="Outi" last="Vaarala">Outi Vaarala</name><affiliation wicri:level="1"><nlm:affiliation>National Institute for Health and Welfare (THL), Helsinki 00300, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>National Institute for Health and Welfare (THL), Helsinki 00300</wicri:regionArea><wicri:noRegion>Helsinki 00300</wicri:noRegion></affiliation></author><author><name sortKey="Nohynek, Hanna" sort="Nohynek, Hanna" uniqKey="Nohynek H" first="Hanna" last="Nohynek">Hanna Nohynek</name><affiliation wicri:level="1"><nlm:affiliation>National Institute for Health and Welfare (THL), Helsinki 00300, Finland.</nlm:affiliation><country xml:lang="fr">Finlande</country><wicri:regionArea>National Institute for Health and Welfare (THL), Helsinki 00300</wicri:regionArea><wicri:noRegion>Helsinki 00300</wicri:noRegion></affiliation></author><author><name sortKey="Pasini, Franco Laghi" sort="Pasini, Franco Laghi" uniqKey="Pasini F" first="Franco Laghi" last="Pasini">Franco Laghi Pasini</name><affiliation wicri:level="1"><nlm:affiliation>Internal Medicine, Policlinico Santa Maria alle Scotte, Azienda Ospedaliera Universitaria Senese, Siena 53100, Italy. Medical Science, Surgery, and Neuroscience, University of Siena, Siena 53100, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Internal Medicine, Policlinico Santa Maria alle Scotte, Azienda Ospedaliera Universitaria Senese, Siena 53100, Italy. Medical Science, Surgery, and Neuroscience, University of Siena, Siena 53100</wicri:regionArea><wicri:noRegion>Siena 53100</wicri:noRegion></affiliation></author><author><name sortKey="Montomoli, Emanuele" sort="Montomoli, Emanuele" uniqKey="Montomoli E" first="Emanuele" last="Montomoli">Emanuele Montomoli</name><affiliation wicri:level="1"><nlm:affiliation>Molecular and Developmental Medicine, University of Siena, Siena 53100, Italy. VisMederi Srl, Siena 53100, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Molecular and Developmental Medicine, University of Siena, Siena 53100, Italy. VisMederi Srl, Siena 53100</wicri:regionArea><wicri:noRegion>Siena 53100</wicri:noRegion></affiliation></author><author><name sortKey="Trombetta, Claudia" sort="Trombetta, Claudia" uniqKey="Trombetta C" first="Claudia" last="Trombetta">Claudia Trombetta</name><affiliation wicri:level="1"><nlm:affiliation>Molecular and Developmental Medicine, University of Siena, Siena 53100, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Molecular and Developmental Medicine, University of Siena, Siena 53100</wicri:regionArea><wicri:noRegion>Siena 53100</wicri:noRegion></affiliation></author><author><name sortKey="Adams, Christopher M" sort="Adams, Christopher M" uniqKey="Adams C" first="Christopher M" last="Adams">Christopher M. Adams</name><affiliation wicri:level="2"><nlm:affiliation>Stanford University Mass Spectrometry, Stanford University School of Medicine, Palo Alto, CA 94305 USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>Stanford University Mass Spectrometry, Stanford University School of Medicine, Palo Alto</wicri:cityArea></affiliation></author><author><name sortKey="Rothbard, Jonathan" sort="Rothbard, Jonathan" uniqKey="Rothbard J" first="Jonathan" last="Rothbard">Jonathan Rothbard</name><affiliation wicri:level="2"><nlm:affiliation>Immunology, Stanford University School of Medicine, Palo Alto, CA 94305, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Immunology, Stanford University School of Medicine, Palo Alto, CA 94305</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Steinman, Lawrence" sort="Steinman, Lawrence" uniqKey="Steinman L" first="Lawrence" last="Steinman">Lawrence Steinman</name><affiliation wicri:level="2"><nlm:affiliation>Neurology and Neuroscience, Stanford University School of Medicine, Stanford, CA 94305, USA. sohail.q.ahmed@gsk.com steinman@stanford.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Neurology and Neuroscience, Stanford University School of Medicine, Stanford, CA 94305</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author></analytic><series><title level="j">Science translational medicine</title><idno type="eISSN">1946-6242</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Sequence</term><term>Antibodies, Viral (immunology)</term><term>Cell Line</term><term>Child</term><term>Cross Reactions (immunology)</term><term>Humans</term><term>Immunity</term><term>Immunoglobulin G (blood)</term><term>Influenza Vaccines (immunology)</term><term>Influenza, Human (immunology)</term><term>Influenza, Human (virology)</term><term>Mass Spectrometry</term><term>Molecular Sequence Data</term><term>Narcolepsy (immunology)</term><term>Orexin Receptors (chemistry)</term><term>Orexin Receptors (immunology)</term><term>Peptides (chemistry)</term><term>Peptides (immunology)</term><term>RNA-Binding Proteins (chemistry)</term><term>RNA-Binding Proteins (immunology)</term><term>Reassortant Viruses (immunology)</term><term>Seasons</term><term>Sequence Alignment</term><term>Vaccination</term><term>Viral Core Proteins (chemistry)</term><term>Viral Core Proteins (immunology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Alignement de séquences</term><term>Anticorps antiviraux (immunologie)</term><term>Données de séquences moléculaires</term><term>Enfant</term><term>Grippe humaine (immunologie)</term><term>Grippe humaine (virologie)</term><term>Humains</term><term>Immunité</term><term>Immunoglobuline G (sang)</term><term>Lignée cellulaire</term><term>Narcolepsie (immunologie)</term><term>Peptides ()</term><term>Peptides (immunologie)</term><term>Protéines de liaison à l'ARN ()</term><term>Protéines de liaison à l'ARN (immunologie)</term><term>Protéines du core viral ()</term><term>Protéines du core viral (immunologie)</term><term>Réactions croisées (immunologie)</term><term>Récepteurs des orexines ()</term><term>Récepteurs des orexines (immunologie)</term><term>Saisons</term><term>Spectrométrie de masse</term><term>Séquence d'acides aminés</term><term>Vaccination</term><term>Vaccins antigrippaux (immunologie)</term><term>Virus recombinants (immunologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Immunoglobulin G</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Orexin Receptors</term><term>Peptides</term><term>RNA-Binding Proteins</term><term>Viral Core Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Antibodies, Viral</term><term>Influenza Vaccines</term><term>Orexin Receptors</term><term>Peptides</term><term>RNA-Binding Proteins</term><term>Viral Core Proteins</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Anticorps antiviraux</term><term>Grippe humaine</term><term>Narcolepsie</term><term>Peptides</term><term>Protéines de liaison à l'ARN</term><term>Protéines du core viral</term><term>Réactions croisées</term><term>Récepteurs des orexines</term><term>Vaccins antigrippaux</term><term>Virus recombinants</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Cross Reactions</term><term>Influenza, Human</term><term>Narcolepsy</term><term>Reassortant Viruses</term></keywords><keywords scheme="MESH" qualifier="sang" xml:lang="fr"><term>Immunoglobuline G</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Grippe humaine</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Influenza, Human</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term><term>Cell Line</term><term>Child</term><term>Humans</term><term>Immunity</term><term>Mass Spectrometry</term><term>Molecular Sequence Data</term><term>Seasons</term><term>Sequence Alignment</term><term>Vaccination</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Alignement de séquences</term><term>Données de séquences moléculaires</term><term>Enfant</term><term>Humains</term><term>Immunité</term><term>Lignée cellulaire</term><term>Peptides</term><term>Protéines de liaison à l'ARN</term><term>Protéines du core viral</term><term>Récepteurs des orexines</term><term>Saisons</term><term>Spectrométrie de masse</term><term>Séquence d'acides aminés</term><term>Vaccination</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The sleep disorder narcolepsy is linked to the HLA-DQB1*0602 haplotype and dysregulation of the hypocretin ligand-hypocretin receptor pathway. Narcolepsy was associated with Pandemrix vaccination (an adjuvanted, influenza pandemic vaccine) and also with infection by influenza virus during the 2009 A(H1N1) influenza pandemic. In contrast, very few cases were reported after Focetria vaccination (a differently manufactured adjuvanted influenza pandemic vaccine). We hypothesized that differences between these vaccines (which are derived from inactivated influenza viral proteins) explain the association of narcolepsy with Pandemrix-vaccinated subjects. A mimic peptide was identified from a surface-exposed region of influenza nucleoprotein A that shared protein residues in common with a fragment of the first extracellular domain of hypocretin receptor 2. A significant proportion of sera from HLA-DQB1*0602 haplotype-positive narcoleptic Finnish patients with a history of Pandemrix vaccination (vaccine-associated narcolepsy) contained antibodies to hypocretin receptor 2 compared to sera from nonnarcoleptic individuals with either 2009 A(H1N1) pandemic influenza infection or history of Focetria vaccination. Antibodies from vaccine-associated narcolepsy sera cross-reacted with both influenza nucleoprotein and hypocretin receptor 2, which was demonstrated by competitive binding using 21-mer peptide (containing the identified nucleoprotein mimic) and 55-mer recombinant peptide (first extracellular domain of hypocretin receptor 2) on cell lines expressing human hypocretin receptor 2. Mass spectrometry indicated that relative to Pandemrix, Focetria contained 72.7% less influenza nucleoprotein. In accord, no durable antibody responses to nucleoprotein were detected in sera from Focetria-vaccinated nonnarcoleptic subjects. Thus, differences in vaccine nucleoprotein content and respective immune response may explain the narcolepsy association with Pandemrix. </div></front></TEI><affiliations><list><country><li>Finlande</li><li>Italie</li><li>Suisse</li><li>États-Unis</li></country><region><li>Californie</li><li>Finlande occidentale</li><li>Massachusetts</li></region><settlement><li>Turku</li></settlement><orgName><li>Université de Turku</li></orgName></list><tree><country name="Italie"><noRegion><name sortKey="Ahmed, Syed Sohail" sort="Ahmed, Syed Sohail" uniqKey="Ahmed S" first="Syed Sohail" last="Ahmed">Syed Sohail Ahmed</name></noRegion><name sortKey="Corti, Lorenzo" sort="Corti, Lorenzo" uniqKey="Corti L" first="Lorenzo" last="Corti">Lorenzo Corti</name><name sortKey="Montomoli, Emanuele" sort="Montomoli, Emanuele" uniqKey="Montomoli E" first="Emanuele" last="Montomoli">Emanuele Montomoli</name><name sortKey="Pallaoro, Michele" sort="Pallaoro, Michele" uniqKey="Pallaoro M" first="Michele" last="Pallaoro">Michele Pallaoro</name><name sortKey="Pasini, Franco Laghi" sort="Pasini, Franco Laghi" uniqKey="Pasini F" first="Franco Laghi" last="Pasini">Franco Laghi Pasini</name><name sortKey="Pezzicoli, Alfredo" sort="Pezzicoli, Alfredo" uniqKey="Pezzicoli A" first="Alfredo" last="Pezzicoli">Alfredo Pezzicoli</name><name sortKey="Rappuoli, Rino" sort="Rappuoli, Rino" uniqKey="Rappuoli R" first="Rino" last="Rappuoli">Rino Rappuoli</name><name sortKey="Rigat, Fabio" sort="Rigat, Fabio" uniqKey="Rigat F" first="Fabio" last="Rigat">Fabio Rigat</name><name sortKey="Trombetta, Claudia" sort="Trombetta, Claudia" uniqKey="Trombetta C" first="Claudia" last="Trombetta">Claudia Trombetta</name></country><country name="États-Unis"><region name="Californie"><name sortKey="Volkmuth, Wayne" sort="Volkmuth, Wayne" uniqKey="Volkmuth W" first="Wayne" last="Volkmuth">Wayne Volkmuth</name></region><name sortKey="Adams, Christopher M" sort="Adams, Christopher M" uniqKey="Adams C" first="Christopher M" last="Adams">Christopher M. Adams</name><name sortKey="Duca, Jose" sort="Duca, Jose" uniqKey="Duca J" first="José" last="Duca">José Duca</name><name sortKey="Narasimhan, Vas" sort="Narasimhan, Vas" uniqKey="Narasimhan V" first="Vas" last="Narasimhan">Vas Narasimhan</name><name sortKey="Rothbard, Jonathan" sort="Rothbard, Jonathan" uniqKey="Rothbard J" first="Jonathan" last="Rothbard">Jonathan Rothbard</name><name sortKey="Steinman, Lawrence" sort="Steinman, Lawrence" uniqKey="Steinman L" first="Lawrence" last="Steinman">Lawrence Steinman</name></country><country name="Suisse"><noRegion><name sortKey="Karle, Anette" sort="Karle, Anette" uniqKey="Karle A" first="Anette" last="Karle">Anette Karle</name></noRegion></country><country name="Finlande"><region name="Finlande occidentale"><name sortKey="Julkunen, Ilkka" sort="Julkunen, Ilkka" uniqKey="Julkunen I" first="Ilkka" last="Julkunen">Ilkka Julkunen</name></region><name sortKey="Nohynek, Hanna" sort="Nohynek, Hanna" uniqKey="Nohynek H" first="Hanna" last="Nohynek">Hanna Nohynek</name><name sortKey="Vaarala, Outi" sort="Vaarala, Outi" uniqKey="Vaarala O" first="Outi" last="Vaarala">Outi Vaarala</name><name sortKey="Vuorela, Arja" sort="Vuorela, Arja" uniqKey="Vuorela A" first="Arja" last="Vuorela">Arja Vuorela</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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