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      The Possible Impact of Vaccination for Seasonal Influenza on Emergence of Pandemic Influenza via Reassortment

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          Abstract

          Background

          One pathway through which pandemic influenza strains might emerge is reassortment from coinfection of different influenza A viruses. Seasonal influenza vaccines are designed to target the circulating strains, which intuitively decreases the prevalence of coinfection and the chance of pandemic emergence due to reassortment. However, individual-based analyses on 2009 pandemic influenza show that the previous seasonal vaccination may increase the risk of pandemic A(H1N1) pdm09 infection. In view of pandemic influenza preparedness, it is essential to understand the overall effect of seasonal vaccination on pandemic emergence via reassortment.

          Methods and Findings

          In a previous study we applied a population dynamics approach to investigate the effect of infection-induced cross-immunity on reducing such a pandemic risk. Here the model was extended by incorporating vaccination for seasonal influenza to assess its potential role on the pandemic emergence via reassortment and its effect in protecting humans if a pandemic does emerge. The vaccination is assumed to protect against the target strains but only partially against other strains. We find that a universal seasonal vaccine that provides full-spectrum cross-immunity substantially reduces the opportunity of pandemic emergence. However, our results show that such effectiveness depends on the strength of infection-induced cross-immunity against any novel reassortant strain. If it is weak, the vaccine that induces cross-immunity strongly against non-target resident strains but weakly against novel reassortant strains, can further depress the pandemic emergence; if it is very strong, the same kind of vaccine increases the probability of pandemic emergence.

          Conclusions

          Two types of vaccines are available: inactivated and live attenuated, only live attenuated vaccines can induce heterosubtypic immunity. Current vaccines are effective in controlling circulating strains; they cannot always help restrain pandemic emergence because of the uncertainty of the oncoming reassortant strains, however. This urges the development of universal vaccines for prevention of pandemic influenza.

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          Most cited references58

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          Emergence and pandemic potential of swine-origin H1N1 influenza virus.

          Influenza viruses cause annual epidemics and occasional pandemics that have claimed the lives of millions. The emergence of new strains will continue to pose challenges to public health and the scientific communities. A prime example is the recent emergence of swine-origin H1N1 viruses that have transmitted to and spread among humans, resulting in outbreaks internationally. Efforts to control these outbreaks and real-time monitoring of the evolution of this virus should provide us with invaluable information to direct infectious disease control programmes and to improve understanding of the factors that determine viral pathogenicity and/or transmissibility.
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            Ecological and immunological determinants of influenza evolution.

            In pandemic and epidemic forms, influenza causes substantial, sometimes catastrophic, morbidity and mortality. Intense selection from the host immune system drives antigenic change in influenza A and B, resulting in continuous replacement of circulating strains with new variants able to re-infect hosts immune to earlier types. This 'antigenic drift' often requires a new vaccine to be formulated before each annual epidemic. However, given the high transmissibility and mutation rate of influenza, the constancy of genetic diversity within lineages over time is paradoxical. Another enigma is the replacement of existing strains during a global pandemic caused by 'antigenic shift'--the introduction of a new avian influenza A subtype into the human population. Here we explore ecological and immunological factors underlying these patterns using a mathematical model capturing both realistic epidemiological dynamics and viral evolution at the sequence level. By matching model output to phylogenetic patterns seen in sequence data collected through global surveillance, we find that short-lived strain-transcending immunity is essential to restrict viral diversity in the host population and thus to explain key aspects of drift and shift dynamics.
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              Containing pandemic influenza with antiviral agents.

              I Longini (2004)
              For the first wave of pandemic influenza or a bioterrorist influenza attack, antiviral agents would be one of the few options to contain the epidemic in the United States until adequate supplies of vaccine were available. The authors use stochastic epidemic simulations to investigate the effectiveness of targeted antiviral prophylaxis to contain influenza. In this strategy, close contacts of suspected index influenza cases take antiviral agents prophylactically. The authors compare targeted antiviral prophylaxis with vaccination strategies. They model an influenza pandemic or bioterrorist attack for an agent similar to influenza A virus (H2N2) that caused the Asian influenza pandemic of 1957-1958. In the absence of intervention, the model predicts an influenza illness attack rate of 33% of the population (95% confidence interval (CI): 30, 37) and an influenza death rate of 0.58 deaths/1,000 persons (95% Cl: 0.4, 0.8). With the use of targeted antiviral prophylaxis, if 80% of the exposed persons maintained prophylaxis for up to 8 weeks, the epidemic would be contained, and the model predicts a reduction to an illness attack rate of 2% (95% Cl: 0.2, 16) and a death rate of 0.04 deaths/1,000 persons (95% CI: 0.0003, 0.25). Such antiviral prophylaxis is nearly as effective as vaccinating 80% of the population. Vaccinating 80% of the children aged less than 19 years is almost as effective as vaccinating 80% of the population. Targeted antiviral prophylaxis has potential as an effective measure for containing influenza until adequate quantities of vaccine are available.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2014
                10 December 2014
                : 9
                : 12
                : e114637
                Affiliations
                [1 ]Modelling and Economics Unit, Centre for Infectious Disease Surveillance and Control, Public Health England, London, United Kingdom
                [2 ]Medical Research Council Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College School of Public Health, London, United Kingdom
                [3 ]Respiratory Diseases Department, Centre for Infectious Disease Surveillance and Control, Public Health England, London, United Kingdom
                [4 ]Statistics Unit, Centre for Infectious Disease Surveillance and Control, Public Health England, London, United Kingdom
                [5 ]Medical Research Council Biostatistics Unit, University Forvie Site, Cambridge, United Kingdom
                [6 ]NIHR Health Protection Research Unit in Modelling Methodology, Department of Infectious Disease Epidemiology, Imperial College School of Public Health, London, United Kingdom
                [7 ]Medical Research Council National Institute for Medical Research, Mill Hill, London, United Kingdom
                National Institutes of Health, United States of America
                Author notes

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

                Conceived and designed the experiments: XZ RP DD PJW AC JWM. Performed the experiments: XZ. Analyzed the data: XZ RP PJW JWM. Contributed reagents/materials/analysis tools: XZ. Wrote the paper: XZ RP PJW JWM.

                Article
                PONE-D-14-20271
                10.1371/journal.pone.0114637
                4262424
                25494180
                0e264f04-f51c-4e3f-ad88-74d4c6b7aa43
                Copyright @ 2014

                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.

                History
                : 6 May 2014
                : 12 November 2014
                Page count
                Pages: 27
                Funding
                This study was supported by the Public Health England. PJW thanks the MRC for Centre funding [grant number MR/K010174/1], and also thanks the UK National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Modelling Methodology at Imperial College London in partnership with Public Health England (PHE) for funding [grant number HPRU-2012-10080]. JWM was supported by MRC NIMR programme No. u117512723. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, the Department of Health, or Public Health England. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Immunology
                Population Biology
                Computer and Information Sciences
                Computerized Simulations
                Medicine and Health Sciences
                Epidemiology
                Infectious Diseases
                Custom metadata
                The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are within the paper.

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