Concordance of interim and final #estimates of #influenza #vaccine #effectiveness: a systematic review (@eurosurveillanc, abstract)

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

Eurosurveillance, Volume 21, Issue 16, 21 April 2016 / Systematic Review

Concordance of interim and final estimates of influenza vaccine effectiveness: a systematic review

VK Leung 1 , BJ Cowling 2 , S Feng 2 , SG Sullivan 1 3

Author affiliations: 1. World Health Organization Collaborating Centre for Reference and Research on Influenza, Peter Doherty Institute for Infection and Immunity, Melbourne, Australia; 2. World Health Organization Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China; 3. Fielding School of Public Health, University of California, Los Angeles, United States

Correspondence: Sheena Sullivan (sheena.sullivan@influenzacentre.org)

Citation style for this article: Leung VK, Cowling BJ, Feng S, Sullivan SG. Concordance of interim and final estimates of influenza vaccine effectiveness: a systematic review. Euro Surveill. 2016;21(16):pii=30202. DOI: http://dx.doi.org/10.2807/1560-7917.ES.2016.21.16.30202

Received:10 September 2015; Accepted:25 January 2016

 

Abstract

The World Health Organization’s Global Influenza Surveillance and Response System meets twice a year to generate a recommendation for the composition of the seasonal influenza vaccine. Interim vaccine effectiveness (VE) estimates provide a preliminary indication of influenza vaccine performance during the season and may be useful for decision making. We reviewed 17 pairs of studies reporting 33 pairs of interim and final estimates using the test-negative design to evaluate whether interim estimates can reliably predict final estimates. We examined features of the study design that may be correlated with interim estimates being substantially different from their final estimates and identified differences related to change in study period and concomitant changes in sample size, proportion vaccinated and proportion of cases. An absolute difference of no more than 10% between interim and final estimates was found for 18 of 33 reported pairs of estimates, including six of 12 pairs reporting VE against any influenza, six of 10 for influenza A(H1N1)pdm09, four of seven for influenza A(H3N2) and two of four for influenza B. While we identified inconsistencies in the methods, the similarities between interim and final estimates support the utility of generating and disseminating preliminary estimates of VE while virus circulation is ongoing.

Keywords: Research; Abstracts; Seasonal Influenza; Vaccines.

——

Advertisements

Modest #Waning of #Influenza #Vaccine #Efficacy and #Antibody #Titers During the 2007–2008 Influenza Season (J Infect Dis., abstract)

[Source: The Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

Modest Waning of Influenza Vaccine Efficacy and Antibody Titers During the 2007–2008 Influenza Season

Joshua G. Petrie1, Suzanne E. Ohmit1, Rachel Truscon1, Emileigh Johnson1, Thomas M. Braun2, Min Z. Levine3, Maryna C. Eichelberger4 and Arnold S. Monto1

Author Affiliations: 1Department of Epidemiology; 2Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor; 3Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia; 4Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland

Correspondence: J. G. Petrie, University of Michigan School of Public Health, 1415 Washington Hts, Ann Arbor, MI 48109 (jpetrie@umich.edu).

Presented in part: IDWeek 2015, San Diega, California, 7–11 October 2015. Poster 1915.

 

Abstract

Background. 

Antibody titers decrease with time following influenza vaccination, raising concerns that vaccine efficacy might wane. However, the relationship between time since vaccination and protection is unclear.

Methods. 

Time-varying vaccine efficacy (VE[t]) was examined in healthy adult participants (age range, 18–49 years) in a placebo-controlled trial of inactivated influenza vaccine (IIV) and live-attenuated influenza vaccine (LAIV) performed during the 2007–2008 influenza season. Symptomatic respiratory illnesses were laboratory-confirmed as influenza. VE(t) was estimated by fitting a smooth function based on residuals from Cox proportional hazards models. Subjects had blood samples collected immediately prior to vaccination, 30 days after vaccination, and at the end of the influenza season for testing by hemagglutination inhibition and neuraminidase inhibition assays.

Results. 

Overall efficacy was 70% (95% confidence interval [CI], 50%–82%) for IIV and 38% (95% CI, 5%–59%) for LAIV. Statistically significant waning was detected for IIV (P = .03) but not LAIV (P = .37); however, IIV remained significantly efficacious until data became sparse at the end of the season. Similarly, antibody titers against influenza virus hemagglutinin and neuraminidase significantly decreased over the season among IIV recipients.

Conclusions. 

Both vaccines were efficacious but LAIV less so. IIV efficacy decreased slowly over time, but the vaccine remained significantly efficacious for the majority of the season.

Key words: influenza – influenza vaccine – efficacy – waning – hemagglutinin – neuraminidase – antibody persistence – longevity of antibody – serologic assays – immune correlates

10.1093/infdis/jiw10410.1093/infdis/jiw106 Received December 22, 2015.

Accepted January 26, 2016.

© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Keywords: Research; Abstracts; Seasonal Influenza; Vaccines.

——

#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.

_____

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.

——

#Oseltamivir #Treatment for #Children with #Influenza-Like Illness in #China: A Cost-Effectiveness Analysis (PLoS One, abstract)

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

Open Access / Peer-reviewed / Research Article

Oseltamivir Treatment for Children with Influenza-Like Illness in China: A Cost-Effectiveness Analysis

Kunling Shen, Tengbin Xiong , Seng Chuen Tan, Jiuhong Wu

PLOS / Published: April 15, 2016 / http://dx.doi.org/10.1371/journal.pone.0153664

 

Abstract

Background

Influenza is a common viral respiratory infection that causes epidemics and pandemics in the human population. Oseltamivir is a neuraminidase inhibitor—a new class of antiviral therapy for influenza. Although its efficacy and safety have been established, there is uncertainty regarding whether influenza-like illness (ILI) in children is best managed by oseltamivir at the onset of illness, and its cost-effectiveness in children has not been studied in China.

Objective

To evaluate the cost-effectiveness of post rapid influenza diagnostic test (RIDT) treatment with oseltamivir and empiric treatment with oseltamivir comparing with no antiviral therapy against influenza for children with ILI.

Methods

We developed a decision-analytic model based on previously published evidence to simulate and evaluate 1-year potential clinical and economic outcomes associated with three managing strategies for children presenting with symptoms of influenza. Model inputs were derived from literature and expert opinion of clinical practice and research in China. Outcome measures included costs and quality-adjusted life year (QALY). All the interventions were compared with incremental cost-effectiveness ratios (ICER).

Results

In base case analysis, empiric treatment with oseltamivir consistently produced the greatest gains in QALY. When compared with no antiviral therapy, the empiric treatment with oseltamivir strategy is very cost effective with an ICER of RMB 4,438. When compared with the post RIDT treatment with oseltamivir, the empiric treatment with oseltamivir strategy is dominant. Probabilistic sensitivity analysis projected that there is a 100% probability that empiric oseltamivir treatment would be considered as a very cost-effective strategy compared to the no antiviral therapy, according to the WHO recommendations for cost-effectiveness thresholds. The same was concluded with 99% probability for empiric oseltamivir treatment being a very cost-effective strategy compared to the post RIDT treatment with oseltamivir.

Conclusion

In the Chinese setting of current health system, our modelling based simulation analysis suggests that empiric treatment with oseltamivir to be a cost-saving and very cost-effective strategy in managing children with ILI.

_____

Citation: Shen K, Xiong T, Tan SC, Wu J (2016) Oseltamivir Treatment for Children with Influenza-Like Illness in China: A Cost-Effectiveness Analysis. PLoS ONE 11(4): e0153664. doi:10.1371/journal.pone.0153664

Editor: Soren Gantt, University of British Columbia, CANADA

Received: December 1, 2015; Accepted: April 2, 2016; Published: April 15, 2016

Copyright: © 2016 Shen 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 project was sponsored by HEC Pharm, a subsidiary of HEC Group. The funder provided support in the form of salaries for authors Tengbin Xiong and Seng Chuen Tan, 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: Tengbin Xiong and Seng Chuen Tan are current employees of IMS Health, which received funds from HEC Pharm for this study. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials. No patents have been applied for relating to the content of the manuscript. None of the authors has any other financial or nonfinancial competing interests.

Keywords: Research; Abstracts; Seasonal Influenza; Antivirals; Oseltamivir; China.

——

#Identification of Low- and High-Impact #Hemagglutinin #AminoAcid #Substitutions That Drive Antigenic #Drift of #Influenza A(#H1N1) Viruses (PLoS Pathog., abstract)

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

Open Access / Peer-reviewed / Research Article

Identification of Low- and High-Impact Hemagglutinin Amino Acid Substitutions That Drive Antigenic Drift of Influenza A(H1N1) Viruses

William T. Harvey, Donald J. Benton, Victoria Gregory, James P. J. Hall, Rodney S. Daniels, Trevor Bedford, Daniel T. Haydon, Alan J. Hay, John W. McCauley, Richard Reeve

PLOS  / Published: April 8, 2016 / http://dx.doi.org/10.1371/journal.ppat.1005526

 

Abstract

Determining phenotype from genetic data is a fundamental challenge. Identification of emerging antigenic variants among circulating influenza viruses is critical to the vaccine virus selection process, with vaccine effectiveness maximized when constituents are antigenically similar to circulating viruses. Hemagglutination inhibition (HI) assay data are commonly used to assess influenza antigenicity. Here, sequence and 3-D structural information of hemagglutinin (HA) glycoproteins were analyzed together with corresponding HI assay data for former seasonal influenza A(H1N1) virus isolates (1997–2009) and reference viruses. The models developed identify and quantify the impact of eighteen amino acid substitutions on the antigenicity of HA, two of which were responsible for major transitions in antigenic phenotype. We used reverse genetics to demonstrate the causal effect on antigenicity for a subset of these substitutions. Information on the impact of substitutions allowed us to predict antigenic phenotypes of emerging viruses directly from HA gene sequence data and accuracy was doubled by including all substitutions causing antigenic changes over a model incorporating only the substitutions with the largest impact. The ability to quantify the phenotypic impact of specific amino acid substitutions should help refine emerging techniques that predict the evolution of virus populations from one year to the next, leading to stronger theoretical foundations for selection of candidate vaccine viruses. These techniques have great potential to be extended to other antigenically variable pathogens.

Author Summary

Influenza A viruses are characterized by rapid antigenic drift: structural changes in B-cell epitopes that facilitate escape from pre-existing immunity. Consequently, seasonal influenza continues to impose a major burden on human health. Accurate quantification of the antigenic impact of specific amino acid substitutions is a pre-requisite for predicting the fitness and evolutionary outcome of variant viruses. Using assays to attribute antigenic variation to amino acid sequence changes we identify substitutions that contribute to antigenic drift and quantify their impact. We show that substitutions identified as low-impact are a critical component of virus antigenic evolution and by including these, as well as the high-impact substitutions often focused on, the accuracy of predicting antigenic phenotypes of emerging viruses from genotype is doubled.

_____

Citation: Harvey WT, Benton DJ, Gregory V, Hall JPJ, Daniels RS, Bedford T, et al. (2016) Identification of Low- and High-Impact Hemagglutinin Amino Acid Substitutions That Drive Antigenic Drift of Influenza A(H1N1) Viruses. PLoS Pathog 12(4): e1005526. doi:10.1371/journal.ppat.1005526

Editor: Scott E. Hensley, The Wistar Institute, UNITED STATES

Received: August 19, 2015; Accepted: March 4, 2016; Published: April 8, 2016

Copyright: © 2016 Harvey 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: Sequences are available from GISAID—http://platform.gisaid.org—and the assay data underpinning this publication (and the GISAID accession numbers of the viruses used) are available from the associated data deposition at doi:10.5525/gla.researchdata.289.

Funding: This research was supported by the Medical Research Council under programme number U117512723 (WTH, VG, DJB, RSD, AJH, JWM) and grant MR/J50032X/1 (WTH), the Wellcome Trust grant number 083224 (JPJH), NIH grant U54GM111274 (TB), and by the Biotechnology and Biological Sciences Research Council Institute Strategic Programme on Livestock Viral Diseases at The Pirbright Institute (RR), grant BB/H009175/1 (RR), and grant BB/E010326/1 (DTH). 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; Seasonal Influenza; H1N1.

——

#Influenza #vaccine #effectiveness in #adults 65 years and older, #Denmark, 2015/16 – a rapid epidemiological and virological assessment (@eurosurveillanc, abstract)

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

Eurosurveillance, Volume 21, Issue 14, 07 April 2016 / Rapid communication

Influenza vaccine effectiveness in adults 65 years and older, Denmark, 2015/16 – a rapid epidemiological and virological assessment

H Emborg 1 , TG Krause 1 , L Nielsen 2 , MK Thomsen 3 , CB Christiansen 4 , MN Skov 5 , XC Nielsen 6 , LS Weinreich 7 , TK Fischer 8 , J Rønn 8 , R Trebbien 8

Author affiliations: 1. Department of Infectious Disease Epidemiology, Statens Serum Institut, Copenhagen, Denmark; 2. Department of Clinical Microbiology, Herlev Hospital, Herlev, Denmark; 3. Department of Clinical Microbiology, Aarhus University Hospital, Aarhus, Denmark; 4. Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark; 5. Department of Clinical Microbiology, Odense University Hospital, Odense C, Denmark; 6. Department of Clinical Microbiology, Slagelse Hospital, Slagelse, Denmark; 7. Department of Clinical Microbiology, Aalborg University Hospital, Aalborg, Denmark; 8. Department of Microbiological Diagnostics and Virology, National Influenza Center, Statens Serum Institut, Copenhagen, Denmark

Correspondence: Hanne-Dorthe Emborg (hde@ssi.dk)

Citation style for this article: Emborg H, Krause TG, Nielsen L, Thomsen MK, Christiansen CB, Skov MN, Nielsen XC, Weinreich LS, Fischer TK, Rønn J, Trebbien R. Influenza vaccine effectiveness in adults 65 years and older, Denmark, 2015/16 – a rapid epidemiological and virological assessment. Euro Surveill. 2016;21(14):pii=30189. DOI: http://dx.doi.org/10.2807/1560-7917.ES.2016.21.14.30189

Received:16 March 2016; Accepted:07 April 2016

 

Abstract

In Denmark, both influenza A(H1N1)pdm09 and influenza B co-circulated in the 2015/16 season. We estimated the vaccine effectiveness (VE) of the trivalent influenza vaccine in patients 65 years and older using the test-negative case–control design. The adjusted VE against influenza A(H1N1)pdm09 was 35.0% (95% confidence interval (CI): 11.1–52.4) and against influenza B 4.1% (95% CI: −22.0 to 24.7). The majority of influenza A(H1N1)pdm09 circulating in 2015/16 belonged to the new genetic subgroup subclade 6B.1.

Keywords: Research; Abstracts; Seasonal Influenza; Vaccines; H1N1pdm09; Denmark.

——

Methodological #evolution of #influenza #vaccine #effectiveness #assessment (The Lancet ID., abstract)

[Source: The Lancet Infectious Diseases, full page: (LINK). Summary.]

Comment

Methodological evolution of influenza vaccine effectiveness assessment

James E Fielding

Published Online: 06 April 2016 / Article has an altmetric score of 10 / DOI: http://dx.doi.org/10.1016/S1473-3099(16)00155-9

 

Summary

Over the last 10 years, the case test-negative study (or test-negative design) has emerged as the preferred observational study design from which to calculate influenza vaccine effectiveness (VE). From humble beginnings as a sentinel physician pilot project in Canada in 2004–05,1 it is now used as far afield as China,2 South Africa,3 and Central America.4 It is a prospective variant of the traditional case-control study design, in which the case (test positive) or control (test negative) status of the study participants is not known at the time of their recruitment into the study: patients presenting with a defined acute respiratory illness are tested for influenza and those who test positive become cases and those who test negative become controls.

(…)

Keywords: Research; Abstracts; Seasonal Influenza; Vaccines.

——