#Pandemic #vaccination #strategies and #influenza severe outcomes during the influenza #H1N1pdm09 pandemic and the post-pandemic influenza season: the Nordic experience (@eurosurveillanc, abstract)

[Source: Eurosurveillance, full page: (LINK). Abstract, edited.]

Eurosurveillance, Volume 21, Issue 16, 21 April 2016 / Surveillance and outbreak report

Pandemic vaccination strategies and influenza severe outcomes during the influenza A(H1N1)pdm09 pandemic and the post-pandemic influenza season: the Nordic experience

JG Cuesta 1 7 , P Aavitsland 2 , H Englund 3 , Ó Gudlaugsson 4 , SH Hauge 5 , O Lyytikäinen 6 , G Sigmundsdóttir 4 , A Tegnell 3 , M Virtanen 6 , the Nordic influenza comparison group 8 , TG Krause 1

Author affiliations: 1. Statens Serum Institut, Copenhagen, Denmark; 2. Epidemi, Kristiansand, Norway; 3. Public Health Agency Sweden, Stockholm, Sweden; 4. Centre for Health Security and Communicable Disease Control, Reykjavik, Iceland; 5. Norwegian Institute of Public Health, Oslo, Norway; 6. National Institute for Health and Welfare, Helsinki, Finland; 7. European Programme for Intervention Epidemiology Training (EPIET), European; Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden.; 8. The Nordic influenza comparison group members are listed at the end of the article

Correspondence: Julita Gil Cuesta (giljulita@gmail.com)

Citation style for this article: Cuesta JG, Aavitsland P, Englund H, Gudlaugsson Ó, Hauge SH, Lyytikäinen O, Sigmundsdóttir G, Tegnell A, Virtanen M, the Nordic influenza comparison group, Krause TG. Pandemic vaccination strategies and influenza severe outcomes during the influenza A(H1N1)pdm09 pandemic and the post-pandemic influenza season: the Nordic experience. Euro Surveill. 2016;21(16):pii=30208. DOI: http://dx.doi.org/10.2807/1560-7917.ES.2016.21.16.30208

Received:14 April 2015; Accepted:03 December 2015

 

Abstract

During the 2009/10 influenza A(H1N1)pdm09 pandemic, the five Nordic countries adopted different approaches to pandemic vaccination. We compared pandemic vaccination strategies and severe influenza outcomes, in seasons 2009/10 and 2010/11 in these countries with similar influenza surveillance systems. We calculated the cumulative pandemic vaccination coverage in 2009/10 and cumulative incidence rates of laboratory confirmed A(H1N1)pdm09 infections, intensive care unit (ICU) admissions and deaths in 2009/10 and 2010/11. We estimated incidence risk ratios (IRR) in a Poisson regression model to compare those indicators between Denmark and the other countries. The vaccination coverage was lower in Denmark (6.1%) compared with Finland (48.2%), Iceland (44.1%), Norway (41.3%) and Sweden (60.0%). In 2009/10 Denmark had a similar cumulative incidence of A(H1N1)pdm09 ICU admissions and deaths compared with the other countries. In 2010/11 Denmark had a significantly higher cumulative incidence of A(H1N1)pdm09 ICU admissions (IRR: 2.4; 95% confidence interval (CI): 1.9–3.0) and deaths (IRR: 8.3; 95% CI: 5.1–13.5). Compared with Denmark, the other countries had higher pandemic vaccination coverage and experienced less A(H1N1)pdm09-related severe outcomes in 2010/11. Pandemic vaccination may have had an impact on severe influenza outcomes in the post-pandemic season. Surveillance of severe outcomes may be used to compare the impact of influenza between seasons and support different vaccination strategies.

Keywords: Research; Abstracts; Pandemic Influenza; Vaccines; H1N1pdm09.

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#Globular Head-Displayed Conserved #Influenza #H1 #Hemagglutinin #Stalk #Epitopes Confer Protection against Heterologous #H1N1 Virus (PLoS One, abstract)

[Source: PLoS One, full page: (LINK). Abstract, edited.]

Open Access / Peer-reviewed / Research Article

Globular Head-Displayed Conserved Influenza H1 Hemagglutinin Stalk Epitopes Confer Protection against Heterologous H1N1 Virus

Miriam Klausberger, Rupert Tscheliessnig, Silke Neff, Raffael Nachbagauer, Teddy John Wohlbold, Monika Wilde, Dieter Palmberger, Florian Krammer, Alois Jungbauer, Reingard Grabherr

PLOS / Published: April 18, 2016 / http://dx.doi.org/10.1371/journal.pone.0153579

 

Abstract

Significant genetic variability in the head region of the influenza A hemagglutinin, the main target of current vaccines, makes it challenging to develop a long-lived seasonal influenza prophylaxis. Vaccines based on the conserved hemagglutinin stalk domain might provide broader cross-reactive immunity. However, this region of the hemagglutinin is immunosubdominant to the head region. Peptide-based vaccines have gained much interest as they allow the immune system to focus on relevant but less immunogenic epitopes. We developed a novel influenza A hemagglutinin-based display platform for H1 hemagglutinin stalk peptides that we identified in an epitope mapping assay using human immune sera and synthetic HA peptides. Flow cytometry and competition assays suggest that the identified stalk sequences do not recapitulate the epitopes of already described broadly neutralizing stalk antibodies. Vaccine constructs displaying 25-mer stalk sequences provided up to 75% protection from lethal heterologous virus challenge in BALB/c mice and induced antibody responses against the H1 hemagglutinin. The developed platform based on a vaccine antigen has the potential to be either used as stand-alone or as prime-vaccine in combination with conventional seasonal or pandemic vaccines for the amplification of stalk-based cross-reactive immunity in humans or as platform to evaluate the relevance of viral peptides/epitopes for protection against influenza virus infection.

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Citation: Klausberger M, Tscheliessnig R, Neff S, Nachbagauer R, Wohlbold TJ, Wilde M, et al. (2016) Globular Head-Displayed Conserved Influenza H1 Hemagglutinin Stalk Epitopes Confer Protection against Heterologous H1N1 Virus. PLoS ONE 11(4): e0153579. doi:10.1371/journal.pone.0153579

Editor: Stephen J. Turner, Monash University, Australia, AUSTRALIA

Received: November 11, 2015; Accepted: March 31, 2016; Published: April 18, 2016

Copyright: © 2016 Klausberger et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the paper and its Supporting Information files.

Funding: MK and MW received funding from the Austrian Science Foundation FWF Doctoral program BioToP-Molecular Technology of Proteins W1224 and DP also was funded by the FWF (P 25092-B13). RT was funded by the Austrian Centre of Industrial Biotechnology (ACIB). ACIB is a non-profit research centre supported by the Federal Ministry of Economy, Family and Youth (BMWJF), the Federal Ministry of Traffic, Innovation and Technology (BMVIT), the Syrian Business Promotion Agency SFG, the Standortagentur Tirol and ZIT – Technology Agency of the City of Vienna through the COMET-Funding Program managed by the Austrian Research Promotion Agency FFG. FK was supported by an Erwin Schrödinger fellowship (J 3232) from the Austrian Science Fund. This work was partially supported by NIH (National Institutes of Health) program project grant 1P01AI097092-01A1 and PATH (Program for Appropriate Technology in Health). The Austrian Centre of Industrial Biotechnology provided support in the form of salaries for authors [RT], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.

Competing interests: Rupert Tscheliessnig was funded by and is employed by the Austrian Centre of Industrial Biotechnology. The Icahn School of Medicine at Mount Sinai together with the University of Natural Resources and Life Sciences has filed a patent on the mentioned display system for influenza epitopes (influenza virus vaccines and uses thereof; application no. 62180405). There are no further patents, products in development or marketed products to declare. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

Keywords: Research; Abstracts; H1N1; Seasonal Influenza; Pandemic Influenza; Vaccines.

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1918 #Influenza #RBD #variants bind and replicate in primary #human #airway #cells regardless of receptor specificity (Virology, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Virology. 2016 Apr 7;493:238-246. doi: 10.1016/j.virol.2016.03.025. [Epub ahead of print]

1918 Influenza receptor binding domain variants bind and replicate in primary human airway cells regardless of receptor specificity.

Davis AS1, Chertow DS2, Kindrachuk J3, Qi L4, Schwartzman LM4, Suzich J2, Alsaaty S3, Logun C3, Shelhamer JH3, Taubenberger JK5.

 

Author information: 1Viral Pathogenesis and Evolution Section, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, United States; Diagnostic Medicine and Pathobiology, Kansas State University College of Veterinary Medicine, Manhattan, KS, United States. 2Viral Pathogenesis and Evolution Section, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, United States; Critical Care Medicine Department, Clinical Center, NIH, Bethesda, MD, United States. 3Critical Care Medicine Department, Clinical Center, NIH, Bethesda, MD, United States. 4Viral Pathogenesis and Evolution Section, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, United States. 5Viral Pathogenesis and Evolution Section, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, United States. Electronic address: taubenbergerj@niaid.nih.gov.

 

Abstract

The 1918 influenza pandemic caused ~50 million deaths. Many questions remain regarding the origin, pathogenicity, and mechanisms of human adaptation of this virus. Avian-adapted influenza A viruses preferentially bind α2,3-linked sialic acids (Sia) while human-adapted viruses preferentially bind α2,6-linked Sia. A change in Sia preference from α2,3 to α2,6 is thought to be a requirement for human adaptation of avian influenza viruses. Autopsy data from 1918 cases, however, suggest that factors other than Sia preference played a role in viral binding and entry to human airway cells. Here, we evaluated binding and entry of five 1918 influenza receptor binding domain variants in a primary human airway cell model along with control avian and human influenza viruses. We observed that all five variants bound and entered cells efficiently and that Sia preference did not predict entry of influenza A virus to primary human airway cells evaluated in this model.

Published by Elsevier Inc.

KEYWORDS: Hemagglutinin; Influenza A virus; Pandemic; Receptor binding

PMID: 27062579 [PubMed – as supplied by publisher]

Keywords: Research; Abstracts; Pandemic Influenza; Spanish Flu; H1N1.

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#Antibody #Persistence in #Adults Two Years after #Vaccination with an #H1N1 2009 #Pandemic #Influenza Virus-Like Particle Vaccine (PLoS One, abstract)

[Source: PLoS One, full page: (LINK). Abstract, edited.]

Open Access / Peer-reviewed / Research Article

Antibody Persistence in Adults Two Years after Vaccination with an H1N1 2009 Pandemic Influenza Virus-Like Particle Vaccine [      ]

Nuriban Valero-Pacheco,  Marisol Pérez-Toledo,  Miguel Ángel Villasís-Keever,  Adriana Núñez-Valencia,  Ilka Boscó-Gárate,  … Bernardo Lozano-Dubernard,  Horacio Lara-Puente,  Clara Espitia,  Celia Alpuche-Aranda,  Laura C. Bonifaz

Published: February 26, 2016 / DOI: 10.1371/journal.pone.0150146

 

Abstract

The influenza virus is a human pathogen that causes epidemics every year, as well as potential pandemic outbreaks, as occurred in 2009. Vaccination has proven to be sufficient in the prevention and containment of viral spreading. In addition to the current egg-based vaccines, new and promising vaccine platforms, such as cell culture-derived vaccines that include virus-like particles (VLPs), have been developed. VLPs have been shown to be both safe and immunogenic against influenza infections. Although antibody persistence has been studied in traditional egg-based influenza vaccines, studies on antibody response durations induced by VLP influenza vaccines in humans are scarce. Here, we show that subjects vaccinated with an insect cell-derived VLP vaccine, in the midst of the 2009 H1N1 influenza pandemic outbreak in Mexico City, showed antibody persistence up to 24 months post-vaccination. Additionally, we found that subjects that reported being revaccinated with a subsequent inactivated influenza virus vaccine showed higher antibody titres to the pandemic influenza virus than those who were not revaccinated. These findings provide insights into the duration of the antibody responses elicited by an insect cell-derived pandemic influenza VLP vaccine and the possible effects of subsequent influenza vaccination on antibody persistence induced by this VLP vaccine in humans.

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Citation: Valero-Pacheco N, Pérez-Toledo M, Villasís-Keever MÁ, Núñez-Valencia A, Boscó-Gárate I, Lozano-Dubernard B, et al. (2016) Antibody Persistence in Adults Two Years after Vaccination with an H1N1 2009 Pandemic Influenza Virus-Like Particle Vaccine. PLoS ONE 11(2): e0150146. doi:10.1371/journal.pone.0150146

Editor: Florian Krammer, Icahn School of Medicine at Mount Sinai, UNITED STATES

Received: December 3, 2015; Accepted: February 9, 2016; Published: February 26, 2016

Copyright: © 2016 Valero-Pacheco et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the paper.

Funding: This work was supported by grants from the Mexican Social Security Institute (IMSS) through the IMSS Fondo de Investigación en Salud projects as follows: FIS/IMSS/PROT/G12/1152 and FIS/IMSS/PROT/PRIO/11/013 awarded to CLM. Funding was also provided by the Mexican National Science and Technology Council (CONACYT), project number CB166946-2011, awarded to RPP. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Keywords: Research; Abstracts; Pandemic Influenza; Vaccines; Mexico.

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Application of Probabilistic Multiple-Bias #Analyses to a Cohort- and a Case-Control Study on the Association between #Pandemrix™and #Narcolepsy (PLoS One, abstract)

[Source: PLoS One, full page: (LINK). Abstract, edited.]

Open Access / Peer-reviewed / Research Article

Application of Probabilistic Multiple-Bias Analyses to a Cohort- and a Case-Control Study on the Association between Pandemrixand Narcolepsy [      ]

Kaatje Bollaerts,  Vivek Shinde,  Gaël Dos Santos,  Germano Ferreira,  Vincent Bauchau,  Catherine Cohet,  Thomas Verstraeten

Published: February 22, 2016 / DOI: 10.1371/journal.pone.0149289

 

Abstract

Background

An increase in narcolepsy cases was observed in Finland and Sweden towards the end of the 2009 H1N1 influenza pandemic. Preliminary observational studies suggested a temporal link with the pandemic influenza vaccine Pandemrix™, leading to a number of additional studies across Europe. Given the public health urgency, these studies used readily available retrospective data from various sources. The potential for bias in such settings was generally acknowledged. Although generally advocated by key opinion leaders and international health authorities, no systematic quantitative assessment of the potential joint impact of biases was undertaken in any of these studies.

Methods

We applied bias-level multiple-bias analyses to two of the published narcolepsy studies: a pediatric cohort study from Finland and a case-control study from France. In particular, we developed Monte Carlo simulation models to evaluate a potential cascade of biases, including confounding by age, by indication and by natural H1N1 infection, selection bias, disease- and exposure misclassification. All bias parameters were evidence-based to the extent possible.

Results

Given the assumptions used for confounding, selection bias and misclassification, the Finnish rate ratio of 13.78 (95% CI: 5.72–28.11) reduced to a median value of 6.06 (2.5th– 97.5th percentile: 2.49–15.1) and the French odds ratio of 5.43 (95% CI: 2.6–10.08) to 1.85 (2.5th—97.5th percentile: 0.85–4.08).

Conclusion

We illustrate multiple-bias analyses using two studies on the Pandemrix-narcolepsy association and advocate their use to better understand the robustness of study findings. Based on our multiple-bias models, the observed Pandemrix-narcolepsy association consistently persists in the Finnish study. For the French study, the results of our multiple-bias models were inconclusive.

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Citation: Bollaerts K, Shinde V, Dos Santos G, Ferreira G, Bauchau V, Cohet C, et al. (2016) Application of Probabilistic Multiple-Bias Analyses to a Cohort- and a Case-Control Study on the Association between Pandemrixand Narcolepsy. PLoS ONE 11(2): e0149289. doi:10.1371/journal.pone.0149289

Editor: Benjamin J. Cowling, University of Hong Kong, HONG KONG

Received: September 22, 2015; Accepted: December 24, 2015; Published: February 22, 2016

Copyright: © 2016 Bollaerts et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the paper and its Supporting Information files.

Funding: This work was supported by GlaxoSmithKline Biologicals SA. GlaxoSmithKline was involved in the design of the study analysis. GlaxoSmithKline paid for all costs associated with the development and the publishing of the present manuscript.

Competing interests: KB, TV received consulting fees from GSK for the conduct of this study. At the time the work was performed, VB, CC, GF, VS were employees at GSK. VB, CC and VS hold stock options/restricted shares from the company. GDS is a full-time consultant on behalf of a GSK group of companies. This does not change the authors’ adherence to all PLOS ONE policies.on sharing data and materials.

Keywords: Research; Abstracts; Pandemic Influenza; Vaccines; Narcolepsy; H1N1pdm09.

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Fit #Assessment of #N95 #Filtering-Facepiece #Respirators in the #US #CDC Strategic National #Stockpile (J Int Soc Respir Prot., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

J Int Soc Respir Prot. 2015;32(2):50-64.

Fit Assessment of N95 Filtering-Facepiece Respirators in the U.S. Centers for Disease Control and Prevention Strategic National Stockpile. [      ]

Bergman M1, Zhuang Z1, Brochu E1, Palmiero A1.

Author information: 1National Institute for Occupational Safety and Health, National Personal Protective Technology Laboratory, Pittsburgh, PA.

 

Abstract

National Institute for Occupational Safety and Health (NIOSH)-approved N95 filtering-facepiece respirators (FFR) are currently stockpiled by the U.S. Centers for Disease Control and Prevention (CDC) for emergency deployment to healthcare facilities in the event of a widespread emergency such as an influenza pandemic. This study assessed the fit of N95 FFRs purchased for the CDC Strategic National Stockpile. The study addresses the question of whether the fit achieved by specific respirator sizes relates to facial size categories as defined by two NIOSH fit test panels. Fit test data were analyzed from 229 test subjects who performed a nine-donning fit test on seven N95 FFR models using a quantitative fit test protocol. An initial respirator model selection process was used to determine if the subject could achieve an adequate fit on a particular model; subjects then tested the adequately fitting model for the nine-donning fit test. Only data for models which provided an adequate initial fit (through the model selection process) for a subject were analyzed for this study. For the nine-donning fit test, six of the seven respirator models accommodated the fit of subjects (as indicated by geometric mean fit factor > 100) for not only the intended NIOSH bivariate and PCA panel sizes corresponding to the respirator size, but also for other panel sizes which were tested for each model. The model which showed poor performance may not be accurately represented because only two subjects passed the initial selection criteria to use this model. Findings are supportive of the current selection of facial dimensions for the new NIOSH panels. The various FFR models selected for the CDC Strategic National Stockpile provide a range of sizing options to fit a variety of facial sizes.

KEYWORDS: N95 Filtering Facepiece Respirators; Respirator Fit; Respirator Fit Test Panel; Strategic National Stockpile

PMID: 26877587 [PubMed]

Keywords: Research; Abstracts; Pandemic Influenza; Facemasks.

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Measuring the #potential of individual #airports for #pandemic #spread over the #world airline #network (BMC Infect Dis., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

BMC Infect Dis. 2016 Feb 9;16(1):70. doi: 10.1186/s12879-016-1350-4.

Measuring the potential of individual airports for pandemic spread over the world airline network. [      ]

Lawyer G1.

Author information: 1Department of Computational Biology, Max Planck Institute for Informatics, Campus E1 4, Saarbrücken, Germany. lawyer@mpi-inf.mpg.de.

 

Abstract

BACKGROUND:

Massive growth in human mobility has dramatically increased the risk and rate of pandemic spread. Macro-level descriptors of the topology of the World Airline Network (WAN) explains middle and late stage dynamics of pandemic spread mediated by this network, but necessarily regard early stage variation as stochastic. We propose that much of this early stage variation can be explained by appropriately characterizing the local network topology surrounding an outbreak’s debut location.

METHODS:

Based on a model of the WAN derived from public data, we measure for each airport the expected force of infection (AEF) which a pandemic originating at that airport would generate, assuming an epidemic process which transmits from airport to airport via scheduled commercial flights. We observe, for a subset of world airports, the minimum transmission rate at which a disease becomes pandemically competent at each airport. We also observe, for a larger subset, the time until a pandemically competent outbreak achieves pandemic status given its debut location. Observations are generated using a highly sophisticated metapopulation reaction-diffusion simulator under a disease model known to well replicate the 2009 influenza pandemic. The robustness of the AEF measure to model misspecification is examined by degrading the underlying model WAN.

RESULTS:

AEF powerfully explains pandemic risk, showing correlation of 0.90 to the transmission level needed to give a disease pandemic competence, and correlation of 0.85 to the delay until an outbreak becomes a pandemic. The AEF is robust to model misspecification. For 97 % of airports, removing 15 % of airports from the model changes their AEF metric by less than 1 %.

CONCLUSIONS:

Appropriately summarizing the size, shape, and diversity of an airport’s local neighborhood in the WAN accurately explains much of the macro-level stochasticity in pandemic outcomes.

PMID: 26861206 [PubMed – in process]

Keywords: Research; Abstracts; Pandemic Influenza.

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