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Antigenic Differences between AS03 Adjuvanted Influenza A (H1N1) Pandemic Vaccines: Implications for Pandemrix-Associated Narcolepsy Risk
BACKGROUND: Narcolepsy results from immune-mediated destruction of hypocretin secreting neurons in hypothalamus, however the triggers and disease mechanisms are poorly understood. Vaccine-attributable risk of narcolepsy reported so far with the AS03 adjuvanted H1N1 vaccination Pandemrix has been man...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4266499/ https://www.ncbi.nlm.nih.gov/pubmed/25501681 http://dx.doi.org/10.1371/journal.pone.0114361 |
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author | Vaarala, Outi Vuorela, Arja Partinen, Markku Baumann, Marc Freitag, Tobias L. Meri, Seppo Saavalainen, Päivi Jauhiainen, Matti Soliymani, Rabah Kirjavainen, Turkka Olsen, Päivi Saarenpää-Heikkilä, Outi Rouvinen, Juha Roivainen, Merja Nohynek, Hanna Jokinen, Jukka Julkunen, Ilkka Kilpi, Terhi |
author_facet | Vaarala, Outi Vuorela, Arja Partinen, Markku Baumann, Marc Freitag, Tobias L. Meri, Seppo Saavalainen, Päivi Jauhiainen, Matti Soliymani, Rabah Kirjavainen, Turkka Olsen, Päivi Saarenpää-Heikkilä, Outi Rouvinen, Juha Roivainen, Merja Nohynek, Hanna Jokinen, Jukka Julkunen, Ilkka Kilpi, Terhi |
author_sort | Vaarala, Outi |
collection | PubMed |
description | BACKGROUND: Narcolepsy results from immune-mediated destruction of hypocretin secreting neurons in hypothalamus, however the triggers and disease mechanisms are poorly understood. Vaccine-attributable risk of narcolepsy reported so far with the AS03 adjuvanted H1N1 vaccination Pandemrix has been manifold compared to the AS03 adjuvanted Arepanrix, which contained differently produced H1N1 viral antigen preparation. Hence, antigenic differences and antibody response to these vaccines were investigated. METHODS AND FINDINGS: Increased circulating IgG-antibody levels to Pandemrix H1N1 antigen were found in 47 children with Pandemrix-associated narcolepsy when compared to 57 healthy children vaccinated with Pandemrix. H1N1 antigen of Arepanrix inhibited poorly these antibodies indicating antigenic difference between Arepanrix and Pandemrix. High-resolution gel electrophoresis quantitation and mass spectrometry identification analyses revealed higher amounts of structurally altered viral nucleoprotein (NP) in Pandemrix. Increased antibody levels to hemagglutinin (HA) and NP, particularly to detergent treated NP, was seen in narcolepsy. Higher levels of antibodies to NP were found in children with DQB1*06∶02 risk allele and in DQB1*06∶02 transgenic mice immunized with Pandemrix when compared to controls. CONCLUSIONS: This work identified 1) higher amounts of structurally altered viral NP in Pandemrix than in Arepanrix, 2) detergent-induced antigenic changes of viral NP, that are recognized by antibodies from children with narcolepsy, and 3) increased antibody response to NP in association of DQB1*06∶02 risk allele of narcolepsy. These findings provide a link between Pandemrix and narcolepsy. Although detailed mechanisms of Pandemrix in narcolepsy remain elusive, our results move the focus from adjuvant(s) onto the H1N1 viral proteins. |
format | Online Article Text |
id | pubmed-4266499 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-42664992014-12-26 Antigenic Differences between AS03 Adjuvanted Influenza A (H1N1) Pandemic Vaccines: Implications for Pandemrix-Associated Narcolepsy Risk Vaarala, Outi Vuorela, Arja Partinen, Markku Baumann, Marc Freitag, Tobias L. Meri, Seppo Saavalainen, Päivi Jauhiainen, Matti Soliymani, Rabah Kirjavainen, Turkka Olsen, Päivi Saarenpää-Heikkilä, Outi Rouvinen, Juha Roivainen, Merja Nohynek, Hanna Jokinen, Jukka Julkunen, Ilkka Kilpi, Terhi PLoS One Research Article BACKGROUND: Narcolepsy results from immune-mediated destruction of hypocretin secreting neurons in hypothalamus, however the triggers and disease mechanisms are poorly understood. Vaccine-attributable risk of narcolepsy reported so far with the AS03 adjuvanted H1N1 vaccination Pandemrix has been manifold compared to the AS03 adjuvanted Arepanrix, which contained differently produced H1N1 viral antigen preparation. Hence, antigenic differences and antibody response to these vaccines were investigated. METHODS AND FINDINGS: Increased circulating IgG-antibody levels to Pandemrix H1N1 antigen were found in 47 children with Pandemrix-associated narcolepsy when compared to 57 healthy children vaccinated with Pandemrix. H1N1 antigen of Arepanrix inhibited poorly these antibodies indicating antigenic difference between Arepanrix and Pandemrix. High-resolution gel electrophoresis quantitation and mass spectrometry identification analyses revealed higher amounts of structurally altered viral nucleoprotein (NP) in Pandemrix. Increased antibody levels to hemagglutinin (HA) and NP, particularly to detergent treated NP, was seen in narcolepsy. Higher levels of antibodies to NP were found in children with DQB1*06∶02 risk allele and in DQB1*06∶02 transgenic mice immunized with Pandemrix when compared to controls. CONCLUSIONS: This work identified 1) higher amounts of structurally altered viral NP in Pandemrix than in Arepanrix, 2) detergent-induced antigenic changes of viral NP, that are recognized by antibodies from children with narcolepsy, and 3) increased antibody response to NP in association of DQB1*06∶02 risk allele of narcolepsy. These findings provide a link between Pandemrix and narcolepsy. Although detailed mechanisms of Pandemrix in narcolepsy remain elusive, our results move the focus from adjuvant(s) onto the H1N1 viral proteins. Public Library of Science 2014-12-15 /pmc/articles/PMC4266499/ /pubmed/25501681 http://dx.doi.org/10.1371/journal.pone.0114361 Text en © 2014 Vaarala et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Vaarala, Outi Vuorela, Arja Partinen, Markku Baumann, Marc Freitag, Tobias L. Meri, Seppo Saavalainen, Päivi Jauhiainen, Matti Soliymani, Rabah Kirjavainen, Turkka Olsen, Päivi Saarenpää-Heikkilä, Outi Rouvinen, Juha Roivainen, Merja Nohynek, Hanna Jokinen, Jukka Julkunen, Ilkka Kilpi, Terhi Antigenic Differences between AS03 Adjuvanted Influenza A (H1N1) Pandemic Vaccines: Implications for Pandemrix-Associated Narcolepsy Risk |
title | Antigenic Differences between AS03 Adjuvanted Influenza A (H1N1) Pandemic Vaccines: Implications for Pandemrix-Associated Narcolepsy Risk |
title_full | Antigenic Differences between AS03 Adjuvanted Influenza A (H1N1) Pandemic Vaccines: Implications for Pandemrix-Associated Narcolepsy Risk |
title_fullStr | Antigenic Differences between AS03 Adjuvanted Influenza A (H1N1) Pandemic Vaccines: Implications for Pandemrix-Associated Narcolepsy Risk |
title_full_unstemmed | Antigenic Differences between AS03 Adjuvanted Influenza A (H1N1) Pandemic Vaccines: Implications for Pandemrix-Associated Narcolepsy Risk |
title_short | Antigenic Differences between AS03 Adjuvanted Influenza A (H1N1) Pandemic Vaccines: Implications for Pandemrix-Associated Narcolepsy Risk |
title_sort | antigenic differences between as03 adjuvanted influenza a (h1n1) pandemic vaccines: implications for pandemrix-associated narcolepsy risk |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4266499/ https://www.ncbi.nlm.nih.gov/pubmed/25501681 http://dx.doi.org/10.1371/journal.pone.0114361 |
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