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Antibody Affinity Against 2009 A/H1N1 Influenza and Pandemrix Vaccine Nucleoproteins Differs Between Childhood Narcolepsy Patients and Controls
Lund Univ, Skåne Univ Hosp SUS, Dept Clin Sci, Clin Res Ctr.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
Lund Univ, Skåne Univ Hosp SUS, Dept Clin Sci, Clin Res Ctr.
Karolinska Inst, Dept Clin Neurosci.
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2017 (English)In: Viral immunology, ISSN 0882-8245, E-ISSN 1557-8976, Vol. 30, no 8, p. 590-600Article in journal (Refereed) Published
Abstract [en]

Increased narcolepsy incidence was observed in Sweden following the 2009 influenza vaccination with Pandemrix((R)). A substitution of the 2009 nucleoprotein for the 1934 variant has been implicated in narcolepsy development. The aims were to determine (a) antibody levels toward wild-type A/H1N1-2009[A/California/04/2009(H1N1)] (NP-CA2009) and Pandemrix-[A/Puerto Rico/8/1934(H1N1)] (NP-PR1934) nucleoproteins in 43 patients and 64 age-matched controls; (b) antibody affinity in reciprocal competitive assays in 11 childhood narcolepsy patients compared with 21 age-matched controls; and (c) antibody levels toward wild-type A/H1N1-2009[A/California/04/2009(H1N1)] (H1N1 NS1), not a component of the Pandemrix vaccine. In vitro transcribed and translated S-35-methionine-labeled H1N1 influenza A virus proteins were used in radiobinding reciprocal competition assays to estimate antibody levels and affinity (Kd). Childhood patients had higher NP-CA2009 (p=0.0339) and NP-PR1934 (p=0.0246) antibody levels compared with age-matched controls. These childhood controls had lower NP-CA2009 (p=0.0221) and NP-PR1934 (p=0.00619) antibodies compared with controls 13 years or older. In contrast, in patients 13 years or older, the levels of NP-PR1934 (p=0.279) and NP-CA2009 (p=0.0644) antibodies did not differ from the older controls. Childhood antibody affinity (Kd) against NP-CA2009 was comparable between controls (68ng/mL) and patients (74ng/mL; p=0.21) with NP-CA2009 and NP-PR1934 displacement (controls: 165ng/mL; patients: 199ng/mL; p=0.48). In contrast, antibody affinity against NP-PR1934 was higher in controls with either NP-PR1934 (controls: 9ng/mL; patients: 20ng/mL; p=0.0031) or NP-CA2009 (controls: 14ng/mL; patients: 23ng/mL; p=0.0048). A/H1N1-NS1 antibodies were detected in 0/43 of the narcolepsy patients compared with 3/64 (4.7%) controls (p=0.272). Similarly, none (0/11) of the childhood patients and 1/21 (4.8%) of the childhood controls had A/H1N1-NS1 antibodies. The higher antibody affinities against NP-PR1934 in controls suggest better protection against wild-type virus. In contrast, the reduced NP-PR1934 antibody affinities among childhood narcolepsy patients suggest poor protection from the wild-type A/H1N1 virus and possibly increased risk for viral damage.

Place, publisher, year, edition, pages
2017. Vol. 30, no 8, p. 590-600
Keywords [en]
radiobinding assay, Pandemrix-vaccination, A, H1N1 pandemic, vaccine-related-adverse-reactions
National Category
Immunology
Identifiers
URN: urn:nbn:se:uu:diva-337750DOI: 10.1089/vim.2017.0066ISI: 000412648900008PubMedID: 28796576OAI: oai:DiVA.org:uu-337750DiVA, id: diva2:1170873
Funder
Gunvor och Josef Anérs stiftelseAvailable from: 2018-01-04 Created: 2018-01-04 Last updated: 2018-01-04Bibliographically approved

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