scholarly journals 0773 Why Did Pandemrix Trigger Narcolepsy? A Structural Approach

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A293-A294
Author(s):  
V Peris Sempere ◽  
A Ambati ◽  
G Luo ◽  
L Lin ◽  
E Mignot
Keyword(s):  
Influenza A ◽  
Promising Result ◽  
Influenza Pandemic ◽  
Vaccination Campaign ◽  
Type I ◽  
Cell Reactivity ◽  
Binding Core ◽  
The Difference ◽  
T Cell Reactivity ◽  
2009 Influenza Pandemic

Abstract Introduction The 2009 Pandemrix influenza A pH1N1 vaccine has been linked to an increased number of Narcolepsy type I onsets in children across Europe whereas administration of a very similar adjuvanted vaccine, Arepanrix, had little effects in Canada. One possible explanation for the difference may be vaccine composition differences that could modify peptide binding to narcolepsy associated HLA-DQ0602 allele, as viral extracts for these two vaccines used distinct processes in different factories. Other explanations may involve differences in vaccination timing in relation to the pandemic H1N1 infection wave, or other environmental factors. We have previously compared the amino acid sequence of the Hemagglutinin (HA) component of the Pandemrix and the 2010 Arepanrix vaccine, finding possible contributors, but excluding most of these after DQ0602-tetramer analysis of T cell reactivity in narcolepsy versus controls. Methods Mass spectrometric characterization of multiple additional batches of Pandemrix and Arepanrix used during 2009 influenza pandemic vaccination campaign was performed. Results In addition to confirming previously published results such as increased deamidation of hemagglutinin (HA) (146N>D) in Pandemrix (p=2.1e-9), we identified novel differences, including a significant 2-fold post-translation deamidation increase in 277N in Arepanrix versus Pandemrix (p=0.032), together with increased 2-fold glycosylation in the 286-323 positions in Arepanrix (p=0.00036). The 277 N to D/isoD substitution is located in pocket 1 of the binding core of a strong binder NAGSGIIIS, (< 10% rank) for HLA-DQ0602 allele and abolishes epitope binding. The increased glycosylation in Arepanrix occurs in the immediate flanking area of the same 277N epitope and could also reduce DQ0602 presentation of the same epitope through differential binding and/or proteolysis of HA in this region of the molecules. As CD4 T cells recognizing this epitope have been reported to be significantly increased in narcolepsy versus DQ0602 controls, with possible mimicry with homologous hypocretin sequence. Conclusion These changes could explain why Arepanrix was less narcolepsy inducing. Confirmatory studies, as well as studies of all novel changes observed, are ongoing, but this is a promising result. Support Wake Up Narcolepsy

scholarly journals Children under 10 years of age were more affected by the 2018/19 influenza A(H1N1)pdm09 epidemic in Canada: ‎possible cohort effect following the 2009 influenza pandemic

2019 ◽  
Vol 24 (15) ◽  
Author(s):  
Danuta M Skowronski ◽  
Siobhan Leir ◽  
Gaston De Serres ◽  
Michelle Murti ◽  
James A Dickinson ◽  
...  
Keyword(s):  
General Population ◽  
Influenza A ◽  
Influenza Pandemic ◽  
Age Distribution ◽  
Cohort Effect ◽  
Surveillance Network ◽  
Medical Visits ◽  
Influenza A H1n1 ◽  
2009 Influenza Pandemic ◽  
Negative Controls

Introduction Findings from the community-based Canadian Sentinel Practitioner Surveillance Network (SPSN) suggest children were more affected by the 2018/19 influenza A(H1N1)pdm09 epidemic. Aim To compare the age distribution of A(H1N1)pdm09 cases in 2018/19 to prior seasonal influenza epidemics in Canada. Methods The age distribution of unvaccinated influenza A(H1N1)pdm09 cases and test-negative controls were compared across A(H1N1)pdm09-dominant epidemics in 2018/19, 2015/16 and 2013/14 and with the general population of SPSN provinces. Similar comparisons were undertaken for influenza A(H3N2)-dominant epidemics. Results In 2018/19, more influenza A(H1N1)pdm09 cases were under 10 years old than controls (29% vs 16%; p < 0.001). In particular, children aged 5–9 years comprised 14% of cases, greater than their contribution to controls (4%) or the general population (5%) and at least twice their contribution in 2015/16 (7%; p < 0.001) or 2013/14 (5%; p < 0.001). Conversely, children aged 10–19 years (11% of the population) were under-represented among A(H1N1)pdm09 cases versus controls in 2018/19 (7% vs 12%; p < 0.001), 2015/16 (7% vs 13%; p < 0.001) and 2013/14 (9% vs 12%; p = 0.12). Conclusion Children under 10 years old contributed more to outpatient A(H1N1)pdm09 medical visits in 2018/19 than prior seasonal epidemics in Canada. In 2018/19, all children under 10 years old were born after the 2009 A(H1N1)pdm09 pandemic and therefore lacked pandemic-induced immunity. In addition, more than half those born after 2009 now attend school (i.e. 5–9-year-olds), a socio-behavioural context that may enhance transmission and did not apply during prior A(H1N1)pdm09 epidemics.

scholarly journals Pandemic H1N1 influenza: predicting the course of a pandemic and assessing the efficacy of the planned vaccination programme in the United States

2009 ◽  
Vol 14 (41) ◽  
Author(s):  
S Towers ◽  
Z Feng
Keyword(s):  
United States ◽  
Influenza A ◽  
Influenza Pandemic ◽  
Vaccination Campaign ◽  
H1n1 Influenza ◽  
The United States ◽  
Pandemic H1n1 ◽  
Pandemic H1n1 Influenza ◽  
Influenza A H1n1 ◽  
Control And Prevention

We use data on confirmed cases of pandemic influenza A(H1N1), disseminated by the United States Centers for Disease Control and Prevention(US CDC), to fit the parameters of a seasonally forced Susceptible, Infective, Recovered (SIR) model. We use the resulting model to predict the course of the H1N1 influenza pandemic in autumn 2009, and we assess the efficacy of the planned CDC H1N1 vaccination campaign. The model predicts that there will be a significant wave in autumn, with 63% of the population being infected, and that this wave will peak so early that the planned CDC vaccination campaign will likely not have a large effect on the total number of people ultimately infected by the pandemic H1N1 influenza virus.

scholarly journals The RIG-I Agonist 3pRNA Synergizes with Checkpoint Blockade in Cancer Immunotherapy

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3436-3436 ◽  
Author(s):  
Simon Heidegger ◽  
Diana Kreppel ◽  
Michael Bscheider ◽  
Alexander Wintges ◽  
Sarah Bek ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Immunity ◽  
Conflicts Of Interest ◽  
Cytotoxic T Cells ◽  
Type I ◽  
Therapeutic Success ◽  
Cell Reactivity ◽  
T Cell Reactivity ◽  
Systemic Antibiotics

Abstract Antibody-mediated targeting of regulatory T cell receptors such as CTLA-4 has been shown to enhance anti-tumor immune responses against several cancer entities including malignant melanoma. Yet, therapeutic success in patients remains variable underscoring the need for novel combinatorial approaches. Here we established a vaccination protocol that combines selective engagement of the nucleic acid-sensing pattern recognition receptor RIG-I, antigen and CTLA-4-blockade. We found that vaccination together with RIG-I ligation strongly synergized with CTLA-4 blockade to induce expansion and activation of antigen-specific CD8+ T cells and potent anti-tumor immunity. Cross-priming of cytotoxic T cells as well as anti-tumor immunity required the adapter protein MAVS and type I interferon (IFN) signaling and were mediated by dendritic cells. In addition, the benefit of the combined immunization with anti-CTLA-4 was reduced by systemic antibiotics pointing to the requisite of an intact commensal microbiota in this context. Together, our findings describe a novel combinatorial strategy that may form the basis for the design of new type I IFN-based regimens that enhance antigen-specific T cell reactivity against cancer. Disclosures No relevant conflicts of interest to declare.

scholarly journals Pandemic influenza A(H1N1) 2009 breakthrough infections and estimates of vaccine effectiveness in Germany 2009-2010

2010 ◽  
Vol 15 (18) ◽  
Author(s):  
O Wichmann ◽  
P Stöcker ◽  
G Poggensee ◽  
D Altmann ◽  
D Walter ◽  
...  
Keyword(s):  
Pandemic Influenza ◽  
Influenza A ◽  
Influenza Pandemic ◽  
Rapid Assessment ◽  
Screening Method ◽  
Age Groups ◽  
Vaccine Effectiveness ◽  
Influenza A H1n1 ◽  
Reported Data ◽  
2009 Influenza Pandemic

During the 2009 influenza pandemic, a monovalent AS03-adjuvanted vaccine was almost exclusively used in Germany for immunisation against the 2009 pandemic influenza A(H1N1) virus. One-dose vaccination was recommended for all age groups. We applied the screening method for the rapid assessment of vaccine effectiveness (VE) based on reported data of vaccinated and unvaccinated pandemic influenza cases and vaccination coverage estimates. Preliminary results demonstrate excellent VE in persons aged 14-59 years (96.8%; 95% confidence interval (CI): 95.2-97.9) and moderately high VE in those 60 years or older (83.3%; 95% CI: 71.0-90.5).

scholarly journals Global dynamic spatiotemporal pattern of seasonal influenza since 2009 influenza pandemic

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Zhi-Wei Xu ◽  
Zhong-Jie Li ◽  
Wen-Biao Hu
Keyword(s):  
South Africa ◽  
Influenza A ◽  
Seasonal Influenza ◽  
Influenza Pandemic ◽  
Influenza Viruses ◽  
Sub Saharan Africa ◽  
Spatiotemporal Pattern ◽  
Influenza B ◽  
2009 Influenza Pandemic ◽  
Influenza Seasonality

Abstract Background Understanding the global spatiotemporal pattern of seasonal influenza is essential for influenza control and prevention. Available data on the updated global spatiotemporal pattern of seasonal influenza are scarce. This study aimed to assess the spatiotemporal pattern of seasonal influenza after the 2009 influenza pandemic. Methods Weekly influenza surveillance data in 86 countries from 2010 to 2017 were obtained from FluNet. First, the proportion of influenza A in total influenza viruses (PA) was calculated. Second, weekly numbers of influenza positive virus (A and B) were divided by the total number of samples processed to get weekly positive rates of influenza A (RWA) and influenza B (RWB). Third, the average positive rates of influenza A (RA) and influenza B (RB) for each country were calculated by averaging RWA, and RWB of 52 weeks. A Kruskal-Wallis test was conducted to examine if the year-to-year change in PA in all countries were significant, and a universal kriging method with linear semivariogram model was used to extrapolate RA and RB in all countries. Results PA ranged from 0.43 in Zambia to 0.98 in Belarus, and PA in countries with higher income was greater than those countries with lower income. The spatial patterns of high RB were the highest in sub-Saharan Africa, Asia-Pacific region and South America. RWA peaked in early weeks in temperate countries, and the peak of RWB occurred a bit later. There were some temperate countries with non-distinct influenza seasonality (e.g., Mauritius and Maldives) and some tropical/subtropical countries with distinct influenza seasonality (e.g., Chile and South Africa). Conclusions Influenza seasonality is not predictable in some temperate countries, and it is distinct in Chile, Argentina and South Africa, implying that the optimal timing for influenza vaccination needs to be chosen with caution in these unpredictable countries.

scholarly journals Myocarditis Associated with Influenza A H1N1pdm2009

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Akira Ukimura ◽  
Hidetoshi Satomi ◽  
Yukimasa Ooi ◽  
Yumiko Kanzaki
Keyword(s):  
Influenza A ◽  
Case Reports ◽  
Acute Myocarditis ◽  
Influenza Pandemic ◽  
Influenza Infection ◽  
Clinical Severity ◽  
Fulminant Myocarditis ◽  
Circulatory Support ◽  
Influenza Pandemics ◽  
2009 Influenza Pandemic

Acute myocarditis is a well-known complication of influenza infection. The frequency of myocardial involvement in influenza infection varies widely, with the clinical severity ranging from asymptomatic to fulminant varieties. The worst cases can result in death due to impaired cardiac function, although such fulminant myocarditis associated with influenza infection is rare, as shown by previous papers. Following the 2009 influenza pandemic, we reported on the clinical features of a cohort of 15 patients in Japan with H1N1pdm2009 myocarditis. In our subsequent survey of the literature for case reports or series of patients with myocarditis associated with H1N1pdm2009, we identified 58 detailed cases. We discuss here the high prevalence of fulminant myocarditis (36/58, 62%) among patients reported to have myocarditis associated with H1N1pdm2009. Mechanical circulatory support was required in 17 of the patients with fulminant myocarditis, 13 of whom recovered. We stress the need for increased awareness of influenza-associated myocarditis; such knowledge will facilitate earlier diagnosis and treatment of this fatal complication during future influenza pandemics.

Drug susceptibility of influenza A/H3N2 strains co-circulating during 2009 influenza pandemic: First report from Mumbai

2015 ◽  
Vol 29 ◽  
pp. 75-81 ◽  
Author(s):  
Devanshi J. Gohil ◽  
Sweta T. Kothari ◽  
Pramod S. Shinde ◽  
Anand S. Chintakrindi ◽  
Rhuta Meharunkar ◽  
...  
Keyword(s):  
Influenza A ◽  
Influenza Pandemic ◽  
Drug Susceptibility ◽  
First Report ◽  
2009 Influenza Pandemic

scholarly journals Vaccination against influenza: a five-year study in the Post Office

1979 ◽  
Vol 83 (1) ◽  
pp. 157-170 ◽  
Author(s):  
J. W. G. Smith ◽  
R. Pollard
Keyword(s):  
Sickness Absence ◽  
Influenza A ◽  
Vaccination Campaign ◽  
First Year ◽  
Post Office ◽  
Financial Benefit ◽  
Apparent Reduction ◽  
Absence Rate ◽  
The Difference ◽  
And Control

SUMMARYAn injection of influenza vaccine was offered to approximately 60 000 Postal and Telecommunications staff at the beginning of five successive winters. The sickness absence of this group, which included those who accepted the offer of vaccine as well as those who did not, was compared throughout the winter with that of a similar number of employees who were not offered vaccine. The two groups, ‘vaccinated’ and control, comprised the staff of nearly 400 Post Office units scattered throughout Great Britain, the units of the two groups being matched as far as practicable for numbers employed, type of work, region and type of location.The proportion who accepted vaccine fell from 42% in the first year (when only 26 000 Telecommunications employees were offered vaccine) to 35% in the second year, and 25% by the fifth year.With the exception of Telecommunications employees in 1972–73, the sickness absence rate of the group offered vaccine was less than that of the group not offered vaccine, and the difference was evident during the winter observation periods both when influenza was prevalent and when it was not. In the last four years of the study the average difference in sickness absence between the ‘vaccinated’ and control groups was 1.26 days per 100 employees per week during and 1.12 days outside the influenza periods. Moreover, the difference during the influenza periods was greater than could be expected from the acceptance rate of vaccine and the estimated attack rate of influenza. The apparent reduction in sickness absence of the group offered vaccine in comparison with the groupnot offered vaccine represented an appreciable saving in cost.It is suggested than an annual influenza vaccination campaign in industry may produce financial benefit, but that only a proportion of the benefit is due to an improvement in health.

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