Antibody Affinity Against 2009 A/H1N1 Influenza and Pandemrix Vaccine Nucleoproteins Differs Between Childhood Narcolepsy Patients and Controls
Antibody Affinity Against 2009 A/H1N1 Influenza and Pandemrix Vaccine Nucleoproteins Differs Between Childhood Narcolepsy Patients and Controls
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DOI：
10.1089/vim.2017.0066
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发表时间：
2017-10-01
期刊：
影响因子：
2.2
通讯作者：
Lernmark, Ake
中科院分区：
文献类型：
--
作者：
Lind, Alexander;Freyhult, Eva;Lernmark, Ake
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.
