Antibody Affinity Against 2009 A/H1N1 Influenza and Pandemrix Vaccine Nucleoproteins Differs Between Childhood Narcolepsy Patients and Controls
(2017) In Viral Immunology 30(8). p.590-600- Abstract
Increased narcolepsy incidence was observed in Sweden following the 2009 influenza vaccination with Pandemrix(®). 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... (More)
Increased narcolepsy incidence was observed in Sweden following the 2009 influenza vaccination with Pandemrix(®). 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 (35)S-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 (68 ng/mL) and patients (74 ng/mL; p = 0.21) with NP-CA2009 and NP-PR1934 displacement (controls: 165 ng/mL; patients: 199 ng/mL; p = 0.48). In contrast, antibody affinity against NP-PR1934 was higher in controls with either NP-PR1934 (controls: 9 ng/mL; patients: 20 ng/mL; p = 0.0031) or NP-CA2009 (controls: 14 ng/mL; patients: 23 ng/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.
(Less)
- author
- Lind, Alexander
LU
; Freyhult, Eva
; Ramelius, Anita
LU
; Olsson, Tomas
; Arnheim-Dahlström, Lisen
; Lamb, Favelle
; Khademi, Mohsen
; Ambati, Aditya
; Maeurer, Markus
; Lima Bomfim, Izaura
; Fink, Katharina
; Fex, Malin
LU
; Törn, Carina
LU
; Elding Larsson, Helena
LU
and Lernmark, Åke
LU
(Less) - organization
- publishing date
- 2017-08-10
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Viral Immunology
- volume
- 30
- issue
- 8
- pages
- 590 - 600
- publisher
- Mary Ann Liebert, Inc.
- external identifiers
-
- scopus:85031129535
- wos:000412648900008
- pmid:28796576
- ISSN
- 0882-8245
- DOI
- 10.1089/vim.2017.0066
- language
- English
- LU publication?
- yes
- id
- bb4d8a71-f7e4-41c2-bb2a-aa55a2ef6b8b
- date added to LUP
- 2017-09-21 11:20:23
- date last changed
- 2024-03-13 08:08:55
@article{bb4d8a71-f7e4-41c2-bb2a-aa55a2ef6b8b,
abstract = {{<p>Increased narcolepsy incidence was observed in Sweden following the 2009 influenza vaccination with Pandemrix(®). 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 (35)S-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 (68 ng/mL) and patients (74 ng/mL; p = 0.21) with NP-CA2009 and NP-PR1934 displacement (controls: 165 ng/mL; patients: 199 ng/mL; p = 0.48). In contrast, antibody affinity against NP-PR1934 was higher in controls with either NP-PR1934 (controls: 9 ng/mL; patients: 20 ng/mL; p = 0.0031) or NP-CA2009 (controls: 14 ng/mL; patients: 23 ng/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.</p>}},
author = {{Lind, Alexander and Freyhult, Eva and Ramelius, Anita and Olsson, Tomas and Arnheim-Dahlström, Lisen and Lamb, Favelle and Khademi, Mohsen and Ambati, Aditya and Maeurer, Markus and Lima Bomfim, Izaura and Fink, Katharina and Fex, Malin and Törn, Carina and Elding Larsson, Helena and Lernmark, Åke}},
issn = {{0882-8245}},
language = {{eng}},
month = {{08}},
number = {{8}},
pages = {{590--600}},
publisher = {{Mary Ann Liebert, Inc.}},
series = {{Viral Immunology}},
title = {{Antibody Affinity Against 2009 A/H1N1 Influenza and Pandemrix Vaccine Nucleoproteins Differs Between Childhood Narcolepsy Patients and Controls}},
url = {{http://dx.doi.org/10.1089/vim.2017.0066}},
doi = {{10.1089/vim.2017.0066}},
volume = {{30}},
year = {{2017}},
}