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      Maternally Derived Immunity Extends Swine Influenza A Virus Persistence within Farrow-to-Finish Pig Farms: Insights from a Stochastic Event-Driven Metapopulation Model

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          Abstract

          Swine Influenza A Viruses (swIAVs) have been shown to persist in farrow-to-finish pig herds with repeated outbreaks in successive batches, increasing the risk for respiratory disorders in affected animals and being a threat for public health. Although the general routes of swIAV transmission (i.e. direct contact and exposure to aerosols) were clearly identified, the transmission process between batches is still not fully understood. Maternally derived antibodies (MDAs) were stressed as a possible factor favoring within-herd swIAV persistence. However, the relationship between MDAs and the global spread among the different subpopulations in the herds is still lacking. The aim of this study was therefore to understand the mechanisms induced by MDAs in relation with swIAV spread and persistence in farrow-to-finish pig herds. A metapopulation model has been developed representing the population dynamics considering two subpopulations—breeding sows and growing pigs—managed according to batch-rearing system. This model was coupled with a swIAV-specific epidemiological model, accounting for partial passive immunity protection in neonatal piglets and an immunity boost in re-infected animals. Airborne transmission was included by a between-room transmission rate related to the current prevalence of shedding pigs. Maternally derived partial immunity in piglets was found to extend the duration of the epidemics within their batch, allowing for efficient between-batch transmission and resulting in longer swIAV persistence at the herd level. These results should be taken into account in the design of control programmes for the spread and persistence of swIAV in swine herds.

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          Most cited references24

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          The role of swine in the generation of novel influenza viruses.

          The ecology of influenza A viruses is very complicated involving multiple host species and viral genes. Avian species have variable susceptibility to influenza A viruses with wild aquatic birds being the reservoir for this group of pathogens. Occasionally, influenza A viruses are transmitted to mammals from avian species, which can lead to the development of human pandemic strains by direct or indirect transmission to man. Because swine are also susceptible to infection with avian and human influenza viruses, genetic reassortment between these viruses and/or swine influenza viruses can occur. The potential to generate novel influenza viruses has resulted in swine being labelled 'mixing vessels'. The mixing vessel theory is one mechanism by which unique viruses can be transmitted from an avian reservoir to man. Although swine can generate novel influenza viruses capable of infecting man, at present, it is difficult to predict which viruses, if any, will cause a human pandemic. Clearly, the ecology of influenza A viruses is dynamic and can impact human health, companion animals, as well as the health of livestock and poultry for production of valuable protein commodities. For these reasons, influenza is, and will continue to be, a serious threat to the wellbeing of mankind.
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            The immune response and maternal antibody interference to a heterologous H1N1 swine influenza virus infection following vaccination.

            This study investigated the efficacy of a bivalent swine influenza virus (SIV) vaccine in piglets challenged with a heterologous H1N1 SIV isolate. The ability of maternally derived antibodies (MDA) to provide protection against a heterologous challenge and the impact MDA have on vaccine efficacy were also evaluated. Forty-eight MDA(+) pigs and 48 MDA(-) pigs were assigned to 8 different groups. Vaccinated pigs received two doses of a bivalent SIV vaccine at 3 and 5 weeks of age. The infected pigs were challenged at 7 weeks of age with an H1N1 SIV strain heterologous to the H1N1 vaccine strain. Clinical signs, rectal temperature, macroscopic and microscopic lesions, virus excretion, serum and local antibody responses, and influenza-specific T-cell responses were measured. The bivalent SIV vaccine induced a high serum hemagglutination-inhibition (HI) antibody titer against the vaccine virus, but antibodies cross-reacted at a lower level to the challenge virus. This study determined that low serum HI antibodies to a challenge virus induced by vaccination with a heterologous virus provided protection demonstrated by clinical protection and reduced pneumonia and viral excretion. The vaccine was able to prime the local SIV-specific antibody response in the lower respiratory tract as well as inducing a systemic SIV-specific memory T-cell response. MDA alone were capable of suppressing fever subsequent to infection, but other parameters showed reduced protection against infection compared to vaccination. The presence of MDA at vaccination negatively impacted vaccine efficacy as fever and clinical signs were prolonged, and unexpectedly, SIV-induced pneumonia was increased compared to pigs vaccinated in the absence of MDA. MDA also suppressed the serum antibody response and the induction of SIV-specific memory T-cells following vaccination. The results of this study question the effectiveness of the current practice of generating increased MDA levels through sow vaccination in protecting piglets against disease.
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              Modeling Influenza Virus Infection: A Roadmap for Influenza Research

              Influenza A virus (IAV) infection represents a global threat causing seasonal outbreaks and pandemics. Additionally, secondary bacterial infections, caused mainly by Streptococcus pneumoniae, are one of the main complications and responsible for the enhanced morbidity and mortality associated with IAV infections. In spite of the significant advances in our knowledge of IAV infections, holistic comprehension of the interplay between IAV and the host immune response (IR) remains largely fragmented. During the last decade, mathematical modeling has been instrumental to explain and quantify IAV dynamics. In this paper, we review not only the state of the art of mathematical models of IAV infection but also the methodologies exploited for parameter estimation. We focus on the adaptive IR control of IAV infection and the possible mechanisms that could promote a secondary bacterial coinfection. To exemplify IAV dynamics and identifiability issues, a mathematical model to explain the interactions between adaptive IR and IAV infection is considered. Furthermore, in this paper we propose a roadmap for future influenza research. The development of a mathematical modeling framework with a secondary bacterial coinfection, immunosenescence, host genetic factors and responsiveness to vaccination will be pivotal to advance IAV infection understanding and treatment optimization.
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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, CA USA )
                1932-6203
                23 September 2016
                2016
                : 11
                : 9
                : e0163672
                Affiliations
                [1 ]Swine epidemiology and welfare research unit, French Agency for Food, Environmental and Occupational Health & Safety (ANSES), Ploufragan, France
                [2 ]Centre for Health Economics Research & Modeling of Infectious Diseases, Vaccine and Infectious Disease Institute, University of Antwerp, Wilrijk, Belgium
                [3 ]Université Bretagne Loire, Rennes, France
                University of Minnesota College of Veterinary Medicine, UNITED STATES
                Author notes

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

                • Conceptualization: CC NR MA.

                • Formal analysis: CC NR MA.

                • Funding acquisition: NR.

                • Methodology: CC MA.

                • Project administration: NR.

                • Software: LW.

                • Supervision: NR MA.

                • Visualization: CC.

                • Writing – original draft: CC.

                • Writing – review & editing: CC NR LW MA.

                Article
                PONE-D-16-29392
                10.1371/journal.pone.0163672
                5035019
                27662592
                f3546951-be67-4d73-8dae-fde78c5b8b4a
                © 2016 Cador 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.

                History
                : 22 July 2016
                : 12 September 2016
                Page count
                Figures: 5, Tables: 3, Pages: 16
                Funding
                Funding was provided by the CRP Regional Pig Committees for Bretagne, Pays de la Loire and Normandie, and the INAPORC National Pork Council.
                Categories
                Research Article
                Biology and Life Sciences
                Agriculture
                Livestock
                Swine
                Biology and Life Sciences
                Organisms
                Animals
                Vertebrates
                Amniotes
                Mammals
                Swine
                Biology and Life Sciences
                Immunology
                Immunity
                Medicine and Health Sciences
                Immunology
                Immunity
                Research and Analysis Methods
                Model Organisms
                Animal Models
                Pig Models
                Biology and Life Sciences
                Physiology
                Physiological Processes
                Molting
                Medicine and Health Sciences
                Physiology
                Physiological Processes
                Molting
                Biology and Life Sciences
                Population Biology
                Population Dynamics
                Research and Analysis Methods
                Simulation and Modeling
                Biology and Life Sciences
                Behavior
                Animal Behavior
                Animal Sexual Behavior
                Biology and Life Sciences
                Zoology
                Animal Behavior
                Animal Sexual Behavior
                Medicine and Health Sciences
                Epidemiology
                Spatial Epidemiology
                Custom metadata
                All data related to model simulations are provided within the paper.

                Uncategorized
                Uncategorized

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