A/H1N1 hemagglutinin antibodies show comparable affinity in vaccine-related Narcolepsy type 1 and control and are unlikely to contribute to pathogenesis

Lind, A. R.; Marzinotto, Ilaria; Brigatti, Cristina; Ramelius, Anita; Piemonti, Lorenzo; Lampasona, Vito

doi:10.1038/s41598-021-83543-z

Cited by 8 publications

(2 citation statements)

References 41 publications

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“…Using LIPS (Secchi et al, 2020; Burbelo et al, 2005) we measured IgG binding to recombinant nanoluciferase tagged antigens corresponding to SARS-CoV-2 alpha, beta and gamma spike RBD and S2 domains, to HKU1 and OC43 seasonal betacoronaviruses spike S2 domains, and hemagglutinin (HA) antigen of the pandemic Ca2009 H1N1 influenza virus as previously described (Secchi et al, 2020; Lind et al, 2021) (Supplemental Figure 1). Briefly, we cloned recombinant nanoluciferase-tagged monomeric or multimeric antigens and expressed them by transient transfection into Expi293F™ cells (Expi293™ Expression System, Thermo Fisher Scientific Life Technologies, Carlsbad, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

Seasonal betacoronavirus antibodies expansion post BNT161b2 vaccination associates with reduced SARS-CoV-2 VoCs neutralization

Dispinseri

Marzinotto

Brigatti

et al. 2021

Preprint

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SARS-CoV-2 vaccination is known to induce antibodies that recognize also variants of concerns (VoCs) of the virus. However, epidemiological and laboratory evidences indicate that these antibodies have a reduce neutralization ability against VoCs. We studied binding and neutralizing antibodies against the Spike RBD and S2 domains of the Wuhan-Hu-1 virus and its alpha and beta VoCs and of seasonal betacoronaviruses (HKU1 and OC43) in a cohort of 31 health care workers vaccinated with BNT162b2-Comirnaty and prospectively followed post-vaccination. The study of sequential samples collected up to 64 days post-vaccination showed that serological assays measuring IgG against Wuhan-Hu-1 antigens were a poor proxy for VoCs neutralization. In addition, in subjects who had asymptomatic or mild COVID-19 prior to vaccination the loss of nAbs following disease can be rapid and protection from re-infection post-vaccination is often no better than in naïve subjects. Interestingly, in health care workers naïve for SARS-CoV-2 infection, vaccination induced a rapid and transient reactivation of pre-existing seasonal coronaviruses IgG responses that was associated with a subsequent reduced ability to neutralize some VoCs.

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Section: Methodsmentioning

confidence: 99%

Seasonal betacoronavirus antibodies expansion post BNT161b2 vaccination associates with reduced SARS-CoV-2 VoCs neutralization

Dispinseri

Marzinotto

Brigatti

et al. 2021

Preprint

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“…Furthermore, recent data by Lind et al. suggested that HA antibody responses are both qualitatively and quantitatively comparable between NT1 cases and controls, leading these authors to conclude that HA antibodies are likely not involved in the pathogenesis ( 95 ).…”

Section: Clinical and Translational Mechanistic Researchmentioning

confidence: 99%

Narcolepsy and H1N1 influenza immunology a decade later: What have we learned?

Buonocore

Most

2022

Front. Immunol.

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In the wake of the A/California/7/2009 H1N1 influenza pandemic vaccination campaigns in 2009-2010, an increased incidence of the chronic sleep-wake disorder narcolepsy was detected in children and adolescents in several European countries. Over the last decade, in-depth epidemiological and immunological studies have been conducted to investigate this association, which have advanced our understanding of the events underpinning the observed risk. Narcolepsy with cataplexy (defined as type-1 narcolepsy, NT1) is characterized by an irreversible and chronic deficiency of hypocretin peptides in the hypothalamus. The multifactorial etiology is thought to include genetic predisposition, head trauma, environmental triggers, and/or infections (including influenza virus infections), and an increased risk was observed following administration of the A/California/7/2009 H1N1 vaccine Pandemrix (GSK). An autoimmune origin of NT1 is broadly assumed. This is based on its strong association with a predisposing allele (the human leucocyte antigen DQB1*0602) carried by the large majority of NT1 patients, and on links with other immune-related genetic markers affecting the risk of NT1. Presently, hypotheses on the underlying potential immunological mechanisms center on molecular mimicry between hypocretin and peptides within the A/California/7/2009 H1N1 virus antigen. This molecular mimicry may instigate a cross-reactive autoimmune response targeting hypocretin-producing neurons. Local CD4+ T-cell responses recognizing peptides from hypocretin are thought to play a central role in the response. In this model, cross-reactive DQB1*0602-restricted T cells from the periphery would be activated to cross the blood-brain barrier by rare, and possibly pathogen-instigated, inflammatory processes in the brain. Current hypotheses suggest that activation and expansion of cross-reactive T-cells by H1N1/09 influenza infection could have been amplified following the administration of the adjuvanted vaccine, giving rise to a “two-hit” hypothesis. The collective in silico, in vitro, and preclinical in vivo data from recent and ongoing research have progressively refined the hypothetical model of sequential immunological events, and filled multiple knowledge gaps. Though no definitive conclusions can be drawn, the mechanistical model plausibly explains the increased risk of NT1 observed following the 2009-2010 H1N1 pandemic and subsequent vaccination campaign, as outlined in this review.

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Seasonal Betacoronavirus Antibodies’ Expansion Post-BNT161b2 Vaccination Associates with Reduced SARS-CoV-2 VoC Neutralization

et al. 2022

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SARS-CoV-2 vaccination is known to induce antibodies that recognize also variants of concerns (VoCs) of the virus. However, epidemiological and laboratory evidences indicate that these antibodies have a reduced neutralization ability against VoCs. We studied binding and neutralizing antibodies against the Spike protein domains and subunits of the Wuhan-Hu-1 virus and its alpha, beta, delta VoCs and of seasonal betacoronaviruses (HKU1 and OC43) in a cohort of 31 health care workers prospectively followed post-vaccination with BNT162b2-Comirnaty. The study of sequential samples collected up to 64 days post-vaccination showed that serological assays measuring IgG against Wuhan-Hu-1 antigens were a poor proxy for VoC neutralization. In addition, in subjects who had asymptomatic or mild COVID-19 prior to vaccination, the loss of nAbs following disease could be rapid and accompanied by post-vaccination antibody levels similar to those of naïve vaccinees. Interestingly, in health care workers naïve for SARS-CoV-2 infection, vaccination induced a rapid and transient reactivation of pre-existing seasonal coronaviruses IgG responses that was associated with a subsequent reduced ability to neutralize alpha and beta VoCs.

show abstract

A/H1N1 hemagglutinin antibodies show comparable affinity in vaccine-related Narcolepsy type 1 and control and are unlikely to contribute to pathogenesis

Cited by 8 publications

References 41 publications

Seasonal betacoronavirus antibodies expansion post BNT161b2 vaccination associates with reduced SARS-CoV-2 VoCs neutralization

Seasonal betacoronavirus antibodies expansion post BNT161b2 vaccination associates with reduced SARS-CoV-2 VoCs neutralization

Narcolepsy and H1N1 influenza immunology a decade later: What have we learned?

Seasonal Betacoronavirus Antibodies’ Expansion Post-BNT161b2 Vaccination Associates with Reduced SARS-CoV-2 VoC Neutralization

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