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Sample records for inactivating influenza viruses

  1. Seasonal trivalent inactivated influenza vaccine protects against 1918 Spanish influenza virus in ferrets

    Science.gov (United States)

    The influenza H1N1 pandemic of 1918 was one of the worst medical disasters in human history. Recent studies have demonstrated that the hemagglutinin (HA) protein of the 1918 virus and 2009 H1N1 pandemic virus, the latter now a component of the seasonal trivalent inactivated influenza vaccine (TIV),...

  2. Influenza virus inactivated by artificial ribonucleases as a prospective killed virus vaccine.

    Science.gov (United States)

    Fedorova, Antonina A; Goncharova, Elena P; Kovpak, Mikhail P; Vlassov, Valentin V; Zenkova, Marina A

    2012-04-19

    The inactivation of viral particles with agents causing minimal damage to the structure of surface epitopes is a well-established approach for the production of killed virus vaccines. Here, we describe new agents for the inactivation of influenza virus, artificial ribonucleases (aRNases), which are chemical compounds capable of cleaving RNA molecules. Several aRNases were identified, exhibiting significant virucidal activity against the influenza A virus and causing a minimal effect on the affinity of monoclonal antibodies for the inactivated virus. Using a murine model of the influenza virus infection, a high protective activity of the aRNase-inactivated virus as a vaccine was demonstrated. The results of the experiments demonstrate the efficacy of novel chemical agents in the preparation of vaccines against influenza and, perhaps, against other infections caused by RNA viruses. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. THE ANTIGENIC POTENCY OF EPIDEMIC INFLUENZA VIRUS FOLLOWING INACTIVATION BY ULTRAVIOLET RADIATION

    Science.gov (United States)

    Salk, Jonas E.; Lavin, G. I.; Francis, Thomas

    1940-01-01

    A study of the antigenic potency of influenza virus inactivated by ultraviolet radiation has been made. Virus so inactivated is still capable of functioning as an immunizing agent when given to mice by the intraperitoneal route. In high concentrations inactivated virus appears to be nearly as effective as active virus but when quantitative comparisons of the immunity induced by different dilutions are made, it is seen that a hundredfold loss in immunizing capacity occurs during inactivation. Virus in suspensions prepared from the lungs of infected mice is inactivated more rapidly than virus in tissue culture medium. A standard for the comparison of vaccines of epidemic influenza virus is proposed. PMID:19871057

  4. Experience in applying 60Co γ-rays for careful production of inactivated influenza virus vaccines

    International Nuclear Information System (INIS)

    Nordheim, W.; Braeuniger, S.; Schulze, P.; Dittmann, S.; Petzold, G.; Teupel, D.; Luther, P.; Tischner, H.; Baer, M.; Akademie der Wissenschaften der DDR, Leipzig. Zentralinstitut fuer Isotopen- und Strahlenforschung)

    1987-01-01

    Radiation doses between 12 and 13 kGy at 15-20 0 C were sufficient for mild inactivation of influenza viruses. Under these conditions the decisive surface antigens hemagglutinin and neuraminidase were treated with care, and the preparations of influenza viruses revealed good immunogenicity in the animal experiment. Morphologic alterations after application of 20 kGy could not be demonstrated in electron microscopic investigations. Doses of 9.5-9.9 kGy in combination with a very low quantity of HCHO (1:15000) is sufficient for inactivation. Reactivation of influenza viruses after treatment could not be demonstrated. (author)

  5. Development of a dried influenza whole inactivated virus vaccine for pulmonary immunization

    NARCIS (Netherlands)

    Audouy, Sandrine A.L.; van der Schaaf, Gieta; Hinrichs, Wouter L.J.; Frijlink, Henderik W.; Wilschut, Jan; Huckriede, Anke

    2011-01-01

    Stabilization and ease of administration are two ways to substantially improve the use of current vaccines. In the present study an influenza whole inactivated virus (WIV) vaccine was freeze-dried or spray-freeze dried in the presence of inulin as a cryoprotectant. Only spray-freeze drying rendered

  6. Serum and mucosal immune responses to an inactivated influenza virus vaccine induced by epidermal powder immunization.

    Science.gov (United States)

    Chen, D; Periwal, S B; Larrivee, K; Zuleger, C; Erickson, C A; Endres, R L; Payne, L G

    2001-09-01

    Both circulating and mucosal antibodies are considered important for protection against infection by influenza virus in humans and animals. However, current inactivated vaccines administered by intramuscular injection using a syringe and needle elicit primarily circulating antibodies. In this study, we report that epidermal powder immunization (EPI) via a unique powder delivery system elicits both serum and mucosal antibodies to an inactivated influenza virus vaccine. Serum antibody responses to influenza vaccine following EPI were enhanced by codelivery of cholera toxin (CT), a synthetic oligodeoxynucleotide containing immunostimulatory CpG motifs (CpG DNA), or the combination of these two adjuvants. In addition, secretory immunoglobulin A (sIgA) antibodies were detected in the saliva and mucosal lavages of the small intestine, trachea, and vaginal tract, although the titers were much lower than the IgG titers. The local origin of the sIgA antibodies was further shown by measuring antibodies released from cultured tracheal and small intestinal fragments and by detecting antigen-specific IgA-secreting cells in the lamina propria using ELISPOT assays. EPI with a single dose of influenza vaccine containing CT or CT and CpG DNA conferred complete protection against lethal challenges with an influenza virus isolated 30 years ago, whereas a prime and boost immunizations were required for protection in the absence of an adjuvant. The ability to elicit augmented circulating antibody and mucosal antibody responses makes EPI a promising alternative to needle injection for administering vaccines against influenza and other diseases.

  7. The study of side-effects caused by γ-ray inactivation of influenza virus in producing an influenza virus vaccine

    International Nuclear Information System (INIS)

    Migunov, A.I.; Yudin, I.V.; Bannikov, A.I.; Kuznetsov, O.K.

    1985-01-01

    Inactivation of influenza virus by 60 Co-γ-rays in producing an influenza virus vaccine leads to yellowing of the pre-- paration and a decrease in its opalescence. The change in optic properties was only observed at a dose of 5 Gy and higher with sucrose and protein stabilizer simultaneosly present in the solution. It was established that the formation of stained compounds is the result of a radiochemical interaction between intermediate products of radiolysis of these components

  8. Inactivation of influenza A virus H1N1 by disinfection process.

    Science.gov (United States)

    Jeong, Eun Kyo; Bae, Jung Eun; Kim, In Seop

    2010-06-01

    Because any patient, health care worker, or visitor is capable of transmitting influenza to susceptible persons within hospitals, hospital-acquired influenza has been a clinical concern. Disinfection and cleaning of medical equipment, surgical instruments, and hospital environment are important measures to prevent transmission of influenza virus from hospitals to individuals. This study was conducted to evaluate the efficacy of disinfection processes, which can be easily operated at hospitals, in inactivating influenza A virus H1N1 (H1N1). The effects of 0.1 mol/L NaOH, 70% ethanol, 70% 1-propanol, solvent/detergent (S/D) using 0.3% tri (n-butyl)-phosphate and 1.0% Triton X-100, heat, and ethylene oxide (EO) treatments in inactivating H1N1 were determined. Inactivation of H1N1 was kinetically determined by the treatment of disinfectants to virus solution. Also, a surface test method, which involved drying an amount of virus on a surface and then applying the inactivation methods for 1 minute of contact time, was used to determine the virucidal activity. H1N1 was completely inactivated to undetectable levels in 1 minute of 70% ethanol, 70% 1-propanol, and solvent/detergent treatments in the surface tests as well as in the suspension tests. H1N1 was completely inactivated in 1 minute of 0.1 mol/L NaOH treatment in the suspension tests and also effectively inactivated in the surface tests with the log reduction factor of 3.7. H1N1 was inactivated to undetectable levels within 5 minutes, 2.5 minutes, and 1 minute of heat treatment at 70, 80, and 90 degrees C, respectively in the suspension tests. Also, H1N1 was completely inactivated by EO treatment in the surface tests. Common disinfectants, heat, and EO tested in this study were effective at inactivating H1N1. These results would be helpful in implementing effective disinfecting measures to prevent hospital-acquired infections. Copyright 2010 Association for Professionals in Infection Control and Epidemiology, Inc

  9. Influence of virus strain and antigen mass on efficacy of H5 avian influenza inactivated vaccines.

    Science.gov (United States)

    Swayne, D E; Beck, J R; Garcia, M; Stone, H D

    1999-06-01

    The influence of vaccine strain and antigen mass on the ability of inactivated avian influenza (AI) viruses to protect chicks from a lethal, highly pathogenic (HP) AI virus challenge was studied. Groups of 4-week-old chickens were immunized with inactivated vaccines containing one of 10 haemagglutinin subtype H5 AI viruses, one heterologous H7 AI virus or normal allantoic fluid (sham), and challenged 3 weeks later by intra-nasal inoculation with a HP H5 chicken-origin AI virus. All 10 H5 vaccines provided good protection from clinical signs and death, and produced positive serological reactions on agar gel immunodiffusion and haemagglutination inhibition tests. In experiment 1, challenge virus was recovered from the oropharynx of 80% of chickens in the H5 vaccine group. In five H5 vaccine groups, challenge virus was not recovered from the cloaca of chickens. In the other five H5 vaccine groups, the number of chickens with detection of challenge virus from the cloaca was lower than in the sham group (P turkey/Wisconsin/68 (H5N9) was the best vaccine candidate of the H5 strains tested (PD50= 0.006 μg AI antigen). These data demonstrate that chickens vaccinated with inactivated H5 whole virus AI vaccines were protected from clinical signs and death, but usage of vaccine generally did not prevent infection by the challenge virus, as indicated by recovery of virus from the oropharynx. Vaccine use reduced cloacal detection rates, and quantity of virus shed from the cloaca and oropharynx in some vaccine groups, which would potentially reduce environmental contamination and disease transmission in the field.

  10. Estimation by radiation inactivation of the size of functional units governing Sendai and influenza virus fusion

    International Nuclear Information System (INIS)

    Bundo-Morita, K.; Gibson, S.; Lenard, J.

    1987-01-01

    The target sizes associated with fusion and hemolysis carried out by Sendai virus envelope glycoproteins were determined by radiation inactivation analysis. The target size for influenza virus mediated fusion with erythrocyte ghosts at pH 5.0 was also determined for comparison. Sendai-mediated fusion with erythrocyte ghosts at pH 7.0 was likewise inactivated exponentially with increasing radiation dose, yielding a target size of 60 +/- 6 kDa, a value consistent with the molecular weight of a single F-protein molecule. The inactivation curve for Sendai-mediated fusion with cardiolipin liposomes at pH 7.0, however, was more complex. Assuming a multiple target-single hit model, the target consisted of 2-3 units of ca. 60 kDa each. A similar target was seen if the liposome contained 10% gangliosides or if the reaction was measured at pH 5.0, suggesting that fusion occurred by the same mechanism at high and low pH. A target size of 261 +/- 48 kDa was found for Sendai-induced hemolysis, in contrast with influenza, which had a more complex target size for this activity. Sendai virus fusion thus occurs by different mechanisms depending upon the nature of the target membrane, since it is mediated by different functional units. Hemolysis is mediated by a functional unit different from that associated with erythrocyte ghost fusion or with cardiolipin liposome fusion

  11. Thermal Inactivation of avian influenza virus in poultry litter as a method to decontaminate poultry houses.

    Science.gov (United States)

    Stephens, Christopher B; Spackman, Erica

    2017-09-15

    Removal of contaminated material from a poultry house during recovery from an avian influenza virus (AIV) outbreak is costly and labor intensive. Because AIV is not environmentally stable, heating poultry houses may provide an alternative disinfection method. The objective was to determine the time necessary to inactivate AIV in poultry litter at temperatures achievable in a poultry house. Low pathogenic (LP) AIV inactivation was evaluated between 10.0°-48.9°C, at ∼5.5°C intervals and highly pathogenic (HP) AIV inactivation was evaluated between 10.0°-43.3°C, at ∼11°C intervals. Samples were collected at numerous time points for each temperature. Virus isolation in embryonating chicken eggs was conducted to determine if viable virus was present. Each sample was also tested by real-time RT-PCR. Low pathogenicity AIV was inactivated at 1day at 26.7°C or above. At 10.0, 15.6 and 21.1°C, inactivation times increased to 2-5days. Highly pathogenic AIV followed a similar trend; the virus was inactivated after 1day at 43.3°C and 32.2°C, and required 2 and 5days for inactivation at 21.1°C and 10.0°C respectively. While low pathogenicity AIV appeared to be inactivated at a lower temperature than high pathogenicity AIV, this was not due to any difference in the strains, but due to fewer temperature points being evaluated for high pathogenicity. Endpoints for detection by real-time RT-PCR were not found even weeks after the virus was inactivated. This provides a guideline for the time required, at specific temperatures to inactivate AIV in poultry litter and likely on surfaces within the house. Heat treatment will provide an added level of safety to personnel and against further spread by eliminating infectious virus prior to cleaning a house. Published by Elsevier B.V.

  12. Protective efficacy of an inactivated vaccine against H9N2 avian influenza virus in ducks.

    Science.gov (United States)

    Teng, Qiaoyang; Shen, Weixia; Liu, Qinfang; Rong, Guangyu; Chen, Lin; Li, Xuesong; Chen, Hongjun; Yang, Jianmei; Li, Zejun

    2015-09-17

    Wild ducks play an important role in the evolution of avian influenza viruses (AIVs). Domestic ducks in China are known to carry and spread H9N2 AIVs that are thought to have contributed internal genes for the recent outbreak of zoonotic H7N9 virus. In order to protect animal and public health, an effective vaccine is urgently needed to block and prevent the spread of H9N2 virus in ducks. We developed an inactivated H9N2 vaccine (with adjuvant Montanide ISA 70VG) based on an endemic H9N2 AIV and evaluated this vaccine in ducks. The results showed that the inactivated H9N2 vaccine was able to induce a strong and fast humoral immune response in vaccinated ducks. The hemagglutination inhibition titer in the sera increased fast, and reached its peak of 12.3 log2 at 5 weeks post-vaccination in immunized birds and remained at a high level for at least 37 weeks post-vaccination. Moreover, viral shedding was completely blocked in vaccinated ducks after challenge with a homologous H9N2 AIV at both 3 and 37 weeks post-vaccination. The results of this study indicate that the inactivated H9N2 vaccine induces high and prolonged immune response in vaccinated ducks and are efficacious in protecting ducks from H9N2 infection.

  13. Inactivated H7 Influenza Virus Vaccines Protect Mice despite Inducing Only Low Levels of Neutralizing Antibodies.

    Science.gov (United States)

    Kamal, Ram P; Blanchfield, Kristy; Belser, Jessica A; Music, Nedzad; Tzeng, Wen-Pin; Holiday, Crystal; Burroughs, Ashley; Sun, Xiangjie; Maines, Taronna R; Levine, Min Z; York, Ian A

    2017-10-15

    Avian influenza viruses of the H7 hemagglutinin (HA) subtype present a significant public health threat, as evidenced by the ongoing outbreak of human A(H7N9) infections in China. When evaluated by hemagglutination inhibition (HI) and microneutralization (MN) assays, H7 viruses and vaccines are found to induce lower level of neutralizing antibodies (nAb) than do their seasonal counterparts, making it difficult to develop and evaluate prepandemic vaccines. We have previously shown that purified recombinant H7 HA appear to be poorly immunogenic in that they induce low levels of HI and MN antibodies. In this study, we immunized mice with whole inactivated reverse genetics reassortant (RG) viruses expressing HA and neuraminidase (NA) from 3 different H7 viruses [A/Shanghai/2/2013(H7N9), A/Netherlands/219/2003(H7N7), and A/New York/107/2003(H7N2)] or with human A(H1N1)pdm09 (A/California/07/2009-like) or A(H3N2) (A/Perth16/2009) viruses. Mice produced equivalent titers of antibodies to all viruses as measured by enzyme-linked immunosorbent assay (ELISA). However, the antibody titers induced by H7 viruses were significantly lower when measured by HI and MN assays. Despite inducing very low levels of nAb, H7 vaccines conferred complete protection against homologous virus challenge in mice, and the serum antibodies directed against the HA head region were capable of mediating protection. The apparently low immunogenicity associated with H7 viruses and vaccines may be at least partly related to measuring antibody titers with the traditional HI and MN assays, which may not provide a true measure of protective immunity associated with H7 immunization. This study underscores the need for development of additional correlates of protection for prepandemic vaccines. IMPORTANCE H7 avian influenza viruses present a serious risk to human health. Preparedness efforts include development of prepandemic vaccines. For seasonal influenza viruses, protection is correlated with antibody

  14. Trivalent inactivated influenza vaccine effective against influenza A(H3N2) variant viruses in children during the 2014/15 season, Japan

    Science.gov (United States)

    Sugaya, Norio; Shinjoh, Masayoshi; Kawakami, Chiharu; Yamaguchi, Yoshio; Yoshida, Makoto; Baba, Hiroaki; Ishikawa, Mayumi; Kono, Mio; Sekiguchi, Shinichiro; Kimiya, Takahisa; Mitamura, Keiko; Fujino, Motoko; Komiyama, Osamu; Yoshida, Naoko; Tsunematsu, Kenichiro; Narabayashi, Atsushi; Nakata, Yuji; Sato, Akihiro; Taguchi, Nobuhiko; Fujita, Hisayo; Toki, Machiko; Myokai, Michiko; Ookawara, Ichiro; Takahashi, Takao

    2016-01-01

    The 2014/15 influenza season in Japan was characterised by predominant influenza A(H3N2) activity; 99% of influenza A viruses detected were A(H3N2). Subclade 3C.2a viruses were the major epidemic A(H3N2) viruses, and were genetically distinct from A/New York/39/2012(H3N2) of 2014/15 vaccine strain in Japan, which was classified as clade 3C.1. We assessed vaccine effectiveness (VE) of inactivated influenza vaccine (IIV) in children aged 6 months to 15 years by test-negative case–control design based on influenza rapid diagnostic test. Between November 2014 and March 2015, a total of 3,752 children were enrolled: 1,633 tested positive for influenza A and 42 for influenza B, and 2,077 tested negative. Adjusted VE was 38% (95% confidence intervals (CI): 28 to 46) against influenza virus infection overall, 37% (95% CI: 27 to 45) against influenza A, and 47% (95% CI: -2 to 73) against influenza B. However, IIV was not statistically significantly effective against influenza A in infants aged 6 to 11 months or adolescents aged 13 to 15 years. VE in preventing hospitalisation for influenza A infection was 55% (95% CI: 42 to 64). Trivalent IIV that included A/New York/39/2012(H3N2) was effective against drifted influenza A(H3N2) virus, although vaccine mismatch resulted in low VE. PMID:27784529

  15. Hypothiocyanite produced by human and rat respiratory epithelial cells inactivates extracellular H1N2 influenza A virus.

    Science.gov (United States)

    Gingerich, Aaron; Pang, Lan; Hanson, Jarod; Dlugolenski, Daniel; Streich, Rebecca; Lafontaine, Eric R; Nagy, Tamás; Tripp, Ralph A; Rada, Balázs

    2016-01-01

    Our aim was to study whether an extracellular, oxidative antimicrobial mechanism inherent to tracheal epithelial cells is capable of inactivating influenza H1N2 virus. Epithelial cells were isolated from tracheas of male Sprague-Dawley rats. Both primary human and rat tracheobronchial epithelial cells were differentiated in air-liquid interface cultures. A/swine/Illinois/02860/09 (swH1N2) influenza A virions were added to the apical side of airway cells for 1 h in the presence or absence of lactoperoxidase or thiocyanate. Characterization of rat epithelial cells (morphology, Duox expression) occurred via western blotting, PCR, hydrogen peroxide production measurement and histology. The number of viable virions was determined by plaque assays. Statistical difference of the results was analyzed by ANOVA and Tukey's test. Our data show that rat tracheobronchial epithelial cells develop a differentiated, polarized monolayer with high transepithelial electrical resistance, mucin production and expression of dual oxidases. Influenza A virions are inactivated by human and rat epithelial cells via a dual oxidase-, lactoperoxidase- and thiocyanate-dependent mechanism. Differentiated air-liquid interface cultures of rat tracheal epithelial cells provide a novel model to study airway epithelium-influenza interactions. The dual oxidase/lactoperoxidase/thiocyanate extracellular oxidative system producing hypothiocyanite is a fast and potent anti-influenza mechanism inactivating H1N2 viruses prior to infection of the epithelium.

  16. Immune response to inactivated influenza virus vaccine: antibody reactivity with epidemic influenza B viruses of two highly distinct evolutionary lineages.

    Science.gov (United States)

    Pyhälä, R; Kleemola, M; Kumpulainen, V; Vartiainen, E; Lappi, S; Pönkä, A; Cantell, K

    1992-01-01

    Vaccination of adults (healthy female employees potentially capable of transmitting influenza to high-risk persons; n = 104) in autumn 1990 with a trivalent influenza virus vaccine containing B/Yamagata/16/88 induced a low antibody response to B/Finland/150/90, a recent variant of B/Victoria/2/87-like viruses, as compared with the antibody response to B/Finland/172/91, a current variant in the lineage of B/Yamagata/16/88-like viruses. Up to the end of the epidemic season, the antibody status declined but was still significantly better than before the vaccination. The results suggest that the vaccine strain was appropriate for the outbreak of 1990 to 1991 in Finland, but may provide unsatisfactory protection against B/Victoria/2/87-like viruses. Evidence is given that use of Madin-Darby canine kidney (MDCK)-grown virus as an antigen in the haemagglutination inhibition test (HI) may provide more reliable information about the protective antibodies than use of untreated or ether-treated egg-grown viruses. Significantly higher postvaccination and postepidemic antibody titres were recorded among subjects who exhibited the antibody before vaccination than among seronegative subjects. A significantly higher response rate among initially seronegative people than among seropositive people was recorded for antibody to B/Finland/150/90, but no clear evidence was obtained that the pre-existing antibody could have had a negative effect on the antibody production.

  17. Far-UVC light applications: sterilization of MRSA on a surface and inactivation of aerosolized influenza virus

    Science.gov (United States)

    Welch, David; Buonanno, Manuela; Shuryak, Igor; Randers-Pehrson, Gerhard; Spotnitz, Henry M.; Brenner, David J.

    2018-02-01

    Methicillin-resistant Staphylococcus aureus (MRSA) and influenza A virus are two of the major targets for new antimicrobial technologies. In contrast to conventional germicidal lamps emitting primarily at 254 nm, which are both carcinogenic and cataractogenic, recent work has shown the potential of far-UVC technology, mainly between 207 and 222 nm, to be an effective means of sterilization of pathogens without apparent harm to mammalian cells. This is because, due to its strong absorbance in biological materials, far-UVC light cannot penetrate even the outer (non living) layers of human skin or eye; however, because bacteria and viruses are of micrometer or smaller dimensions, far-UVC can penetrate and inactivate them. With this report, we present progress on in vitro tests to inactivate MRSA on a surface using far-UVC light from a laser delivered using an optical diffuser. Qualitative and quantitative results show that this means of far-UVC exposure is adequate to inactivate MRSA with a dose comparable to that which would be required using a conventional germicidal lamp. Also included is a report on progress on inactivation of aerosolized influenza A virus. A custom benchtop aerosol exposure chamber was constructed and used to determine the effectiveness of far- UVC. Results indicate that far-UVC efficiently inactivates airborne aerosolized viruses, with a very low dose of 2 mJ/cm2 of 222-nm light inactivating >95% of aerosolized H1N1 influenza virus. Together these studies help to further establish far-UVC technology as a promising, safe and inexpensive tool for sterilization in many environments.

  18. Influenza virus inactivation for studies of antigenicity and phenotypic neuraminidase inhibitor resistance profiling

    NARCIS (Netherlands)

    M. Jonges (Marcel); W.M. Liu; E. van der Vries (Erhard); R. Jacobi (Ronald); I. Pronk (Inge); C. Boog (Claire); M.P.G. Koopmans D.V.M. (Marion); A. Meijer (Adam); E. Soethout (Ernst)

    2010-01-01

    textabstractIntroduction of a new influenza virus in humans urges quick analysis of its virological and immunological characteristics to determine the impact on public health and to develop protective measures for the human population. At present, however, the necessity of executing pandemic

  19. Virus-Vectored Influenza Virus Vaccines

    Science.gov (United States)

    Tripp, Ralph A.; Tompkins, S. Mark

    2014-01-01

    Despite the availability of an inactivated vaccine that has been licensed for >50 years, the influenza virus continues to cause morbidity and mortality worldwide. Constant evolution of circulating influenza virus strains and the emergence of new strains diminishes the effectiveness of annual vaccines that rely on a match with circulating influenza strains. Thus, there is a continued need for new, efficacious vaccines conferring cross-clade protection to avoid the need for biannual reformulation of seasonal influenza vaccines. Recombinant virus-vectored vaccines are an appealing alternative to classical inactivated vaccines because virus vectors enable native expression of influenza antigens, even from virulent influenza viruses, while expressed in the context of the vector that can improve immunogenicity. In addition, a vectored vaccine often enables delivery of the vaccine to sites of inductive immunity such as the respiratory tract enabling protection from influenza virus infection. Moreover, the ability to readily manipulate virus vectors to produce novel influenza vaccines may provide the quickest path toward a universal vaccine protecting against all influenza viruses. This review will discuss experimental virus-vectored vaccines for use in humans, comparing them to licensed vaccines and the hurdles faced for licensure of these next-generation influenza virus vaccines. PMID:25105278

  20. Influenza (Flu) Viruses

    Science.gov (United States)

    ... Types Seasonal Avian Swine Variant Pandemic Other Influenza (Flu) Viruses Language: English (US) Español Recommend on Facebook ... influenza circulate and cause illness. More Information about Flu Viruses Types of Influenza Viruses Influenza A and ...

  1. Positive regulation of humoral and innate immune responses induced by inactivated Avian Influenza Virus vaccine in broiler chickens.

    Science.gov (United States)

    Abdallah, Fatma; Hassanin, Ola

    2015-12-01

    Avian Influenza (AI) vaccines are widely used for mammals and birds in a trial to eliminate the Avian Influenza virus (AIV) infection from the world. However and up till now the virus is still existed via modulation of its antigenic structure to evade the pressure of host immune responses. For a complete understanding of the immune responses following AI vaccination in chickens, the modulations of the chickens humoral immune responses and interferon-alpha signaling pathway, as a fundamental part of the innate immune responses, were investigated. In our study, we measured the humoral immune response using hemagglutination-inhibition (HI) and enzyme-linked immunosorbent assay (ELISA) tests. In addition, chicken interferon-alpha pathway components was measured at RNA levels using Quantitative Real-time PCR (qRT-PCR) following one dose of inactivated H5N1 influenza vaccine at 14 days of age. In this study, the protective levels of humoral antibody responses were observed at 14, 21 and 28 days following immunization with inactivated (Re-1/H5N1) AI vaccine. In the chicken spleen cells, up regulation in the chicken interferon-alpha pathway components (MX1 & IRF7) was existed as early as 48 h post vaccination and remained until 28 days post vaccination at the endogenous state. However, after the recall with ex-vivo stimulation, the up regulation was more pronounced in the transcriptional factor (IRF7) compared to the antiviral gene (MX1) at 28 days post vaccination. So far, from our results it appears that the inactivated H5N1 vaccine can trigger the chicken interferon-alpha signaling pathway as well as it can elicit protective humoral antibody responses.

  2. Study on Efficacy of Gamma Radiation on the Inactivation of Highly Pathogenic Avian Influenza Virus H5N1 (Thai isolate) in Chicken Meat and Chicken Feces

    International Nuclear Information System (INIS)

    Pinyochon, Wasana; Piadang, Nattayana; Mulika, Ladda; Parchariyanon, Sujira; Vitittheeranon, Arag; Damrongwatapokin, Sudarat

    2006-09-01

    A study on the efficacy of gamma radiation on the inactivation of a highly pathogenic avian influenza virus H5N1 subtype, Thai isolate was carried out. The virus was in the form frozen infected allantoic fluid frozen chicken meat and frozen chicken feces. The result indicated that 9 kilo grey of gamma radiation could completely inactivated 106.0 EID50/ml of AIV infected allantoic fluid and 22 kiel grey and 15 kilo grey of gamma radiation completely inactivate 106.0 EID50/10/ grams of chicken meat and 106.0 EID50/5 grams of chicken feces respectively.

  3. Whole inactivated equine influenza vaccine: Efficacy against a representative clade 2 equine influenza virus, IFNgamma synthesis and duration of humoral immunity.

    Science.gov (United States)

    Paillot, R; Prowse, L; Montesso, F; Huang, C M; Barnes, H; Escala, J

    2013-03-23

    Equine influenza (EI) is a serious respiratory disease of horses induced by the equine influenza virus (EIV). Surveillance, quarantine procedures and vaccination are widely used to prevent or to contain the disease. This study aimed to further characterise the immune response induced by a non-updated inactivated EI and tetanus vaccine, including protection against a representative EIV isolate of the Florida clade 2 sublineage. Seven ponies were vaccinated twice with Duvaxyn IE-T Plus at an interval of four weeks. Five ponies remained unvaccinated. All ponies were experimentally infected with the EIV strain A/eq/Richmond/1/07 two weeks after the second vaccination. Clinical signs of disease were recorded and virus shedding was measured after experimental infection. Antibody response and EIV-specific IFNgamma synthesis, a marker of cell-mediated immunity, were measured at different time points of the study. Vaccination resulted in significant protection against clinical signs of disease induced by A/eq/Richmond/1/07 and reduced virus shedding when challenged at the peak of immunity. Antigenic drift has been shown to reduce protection against EIV infection. Inclusion of a more recent and representative EIV vaccine strain, as recommended by the OIE expert surveillance panel on equine influenza vaccine, may maximise field protection. In addition, significant levels of EIV-specific IFNgamma synthesis by peripheral blood lymphocytes were detected in immunised ponies, which provided a first evidence of CMI stimulation after vaccination with a whole inactivated EIV. Duration of humoral response was also retrospectively investigated in 14 horses vaccinated under field condition and following the appropriate immunisation schedule, up to 599 days after first immunisation. This study revealed that most immunised horses maintained significant levels of cross-reactive SRH antibody for a prolonged period of time, but individual monitoring may be beneficial to identify poor vaccine

  4. Inactivation of low pathogenicity notifiable avian influenza virus and lentogenic Newcastle disease virus following pasteurization in liquid egg products

    Science.gov (United States)

    Sixty seven million cases of shell eggs produced per year in the U.S. are processed as liquid egg product. The U.S. also exports a large amount of egg products. Although the U.S. is normally free of avian influenza, concern about contamination of egg product with these viruses has in the past result...

  5. Characterization of Immune Responses to an Inactivated Avian Influenza Virus Vaccine Adjuvanted with Nanoparticles Containing CpG ODN.

    Science.gov (United States)

    Singh, Shirene M; Alkie, Tamiru N; Abdelaziz, Khaled Taha; Hodgins, Douglas C; Novy, Anastasia; Nagy, Éva; Sharif, Shayan

    2016-06-01

    Avian influenza virus (AIV), a mucosal pathogen, gains entry into host chickens through respiratory and gastrointestinal routes. Most commercial AIV vaccines for poultry consist of inactivated, whole virus with adjuvant, delivered by parenteral administration. Recent advances in vaccine development have led to the application of nanoparticle emulsion delivery systems, such as poly (d,l-lactic-co-glycolic acid) (PLGA) nanoparticles to enhance antigen-specific immune responses. In chickens, the Toll-like receptor 21 ligand, CpG oligodeoxynucleotides (ODNs), have been demonstrated to be immunostimulatory. The objective of this study was to compare the adjuvant potential of CpG ODN 2007 encapsulated in PLGA nanoparticles with nonencapsulated CpG ODN 2007 when combined with a formalin-inactivated H9N2 virus, through intramuscular and aerosol delivery routes. Chickens were vaccinated at days 7 and 21 posthatch for the intramuscular route and at days 7, 21, and 35 for the aerosol route. Antibody-mediated responses were evaluated weekly in sera and lacrimal secretions in specific pathogen-free chickens. The results indicate that nonencapsulated CpG ODN 2007 in inactivated AIV vaccines administered by the intramuscular route generated higher antibody responses compared to the encapsulated CpG ODN 2007 formulation by the same route. Additionally, encapsulated CpG ODN 2007 in AIV vaccines administered by the aerosol route elicited higher mucosal responses compared to nonencapsulated CpG ODN 2007. Future studies may be aimed at evaluating protective immune responses induced with PLGA encapsulation of AIV and adjuvants.

  6. Inactivated H9N2 avian influenza virus vaccine with gel-primed and mineral oil-boosted regimen could produce improved immune response in broiler breeders.

    Science.gov (United States)

    Lee, D-H; Kwon, J-S; Lee, H-J; Lee, Y-N; Hur, W; Hong, Y-H; Lee, J-B; Park, S-Y; Choi, I-S; Song, C-S

    2011-05-01

    The frequent economic losses incurred with H9N2 low pathogenic avian influenza viruses (LPAI) infection have raised serious concerns for the poultry industry. A 1-dose regimen with inactivated H9N2 LPAI vaccine could not prevent vaccinated poultry from becoming infected and from shedding wild viruses. A study was conducted to determine whether a 2-dose regimen of inactivated H9N2 LPAI vaccine could enhance the immunologic response in chickens. Such gel-primed and mineral oil-boosted regimen has produced encouraging results associated with improved immune responses to an H9N2 LPAI. This strategy could be cost effective and helpful for preventing avian influenza virus in the poultry industry.

  7. Evaluation of the U.S. Department of Agriculture's egg pasteurization processes on the inactivation of high pathogenicity avian influenza virus and velogenic Newcastle disease virus in processed egg products

    Science.gov (United States)

    High pathogenicity avian influenza virus (HPAIV) A/chicken/Pennsylvania/1370/1983 (H5N2), and velogenic Newcastle disease virus (vNDV) AMPV-1/California/212676/2002 were inoculated into various egg products then heat treated at various temperatures for 0 to 30 min to determine thermal inactivation p...

  8. The evolving history of influenza viruses and influenza vaccines.

    Science.gov (United States)

    Hannoun, Claude

    2013-09-01

    The isolation of influenza virus 80 years ago in 1933 very quickly led to the development of the first generation of live-attenuated vaccines. The first inactivated influenza vaccine was monovalent (influenza A). In 1942, a bivalent vaccine was produced after the discovery of influenza B. It was later discovered that influenza viruses mutated leading to antigenic changes. Since 1973, the WHO has issued annual recommendations for the composition of the influenza vaccine based on results from surveillance systems that identify currently circulating strains. In 1978, the first trivalent vaccine included two influenza A strains and one influenza B strain. Currently, there are two influenza B lineages circulating; in the latest WHO recommendations, it is suggested that a second B strain could be added to give a quadrivalent vaccine. The history of influenza vaccine and the associated technology shows how the vaccine has evolved to match the evolution of influenza viruses.

  9. Inactivation of Avian Influenza Viruses on Porous and Non-porous Surfaces is Enhanced by Elevating Absolute Humidity.

    Science.gov (United States)

    Guan, J; Chan, M; VanderZaag, A

    2017-08-01

    This study was to evaluate the effect of absolute humidity (AH), a combined factor of temperature and relative humidity (RH), on inactivation of avian influenza viruses (AIVs) on surfaces. Suspensions of the H9N2 or H6N2 AIV were deposited onto carrier surfaces that were either porous (pine wood) or non-porous (stainless steel, synthetic rubber and glass). The inoculated carriers were incubated at 23, 35 or 45°C with 25% or 55% RH for up to 28 days. After incubation, virus was recovered and quantified by chicken embryo assays. The time required to obtain a log 10 reduction in virus infectivity (D-value) was estimated using a linear regression model. At AH of 5.2 g/m 3 (23°C & 25% RH), both viruses survived up to 14 days on the porous surface and for at least 28 days on the non-porous surfaces. The corresponding D-values for H9N2 and H6N2 were 1.49 and 6.90 days on the porous surface and 7.81 and 12.5 days on the non-porous surfaces, respectively. In comparison, at AH of 9.9 g/m 3 (35°C & 25% RH) or 11.3 g/m 3 (23°C & 55% RH), the D-values for H9N2 and H6N2 dropped to ≤0.76 day on the porous surface and to ≤1.81 days on the non-porous surfaces. As the AH continued to rise from 11.3 to 36.0 g/m 3 , the D-value for both viruses decreased further. The relationship between D-value and AH followed a form of y = ax -b for both viruses. The D-values for H9N2 virus were significantly lower (P < 0.05) than those for H6N2 virus. Exposure to ammonia gas at concentrations of 86 and 173 ppm did not significantly alter test results. The findings give evidence that increasing the AH in poultry buildings following an outbreak of disease could greatly reduce the length of time required for their decontamination. © Her Majesty the Queen in Right of Canada 2016.

  10. The effect of gamma-irradiation conditions on the immunogenicity of whole-inactivated Influenza A virus vaccine.

    Science.gov (United States)

    David, Shannon C; Lau, Josyane; Singleton, Eve V; Babb, Rachelle; Davies, Justin; Hirst, Timothy R; McColl, Shaun R; Paton, James C; Alsharifi, Mohammed

    2017-02-15

    Gamma-irradiation, particularly an irradiation dose of 50kGy, has been utilised widely to sterilise highly pathogenic agents such as Ebola, Marburg Virus, and Avian Influenza H5N1. We have reported previously that intranasal vaccination with a gamma-irradiated Influenza A virus vaccine (γ-Flu) results in cross-protective immunity. Considering the possible inclusion of highly pathogenic Influenza strains in future clinical development of γ-Flu, an irradiation dose of 50kGy may be used to enhance vaccine safety beyond the internationally accepted Sterility Assurance Level (SAL). Thus, we investigated the effect of irradiation conditions, including high irradiation doses, on the immunogenicity of γ-Flu. Our data confirm that irradiation at low temperatures (using dry-ice) is associated with reduced damage to viral structure compared with irradiation at room temperature. In addition, a single intranasal vaccination with γ-Flu irradiated on dry-ice with either 25 or 50kGy induced seroconversion and provided complete protection against lethal Influenza A challenge. Considering that low temperature is expected to reduce the protein damage associated with exposure to high irradiation doses, we titrated the vaccine dose to verify the efficacy of 50kGy γ-Flu. Our data demonstrate that exposure to 50kGy on dry-ice is associated with limited effect on vaccine immunogenicity, apparent only when using very low vaccine doses. Overall, our data highlight the immunogenicity of influenza virus irradiated at 50kGy for induction of high titre antibody and cytotoxic T-cell responses. This suggests these conditions are suitable for development of γ-Flu vaccines based on highly pathogenic Influenza A viruses. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Standardization of an inactivated H17N1 avian influenza vaccine and efficacy against A/Chicken/Italy/13474/99 high-pathogenicity virus infection.

    Science.gov (United States)

    Di Trani, L; Cordioli, P; Falcone, E; Lombardi, G; Moreno, A; Sala, G; Tollis, M

    2003-01-01

    The minimum requirements for assessing the immunogenicity of an experimental avian influenza (AI) vaccine prepared from inactivated A/Turkey/Italy/2676/99 (H7N1) low-pathogenicity (LP) AI (LPAI) virus were determined in chickens of different ages. A correlation between the amount of hemagglutinin (HA) per dose of vaccine and the protection against clinical signs of disease and infection by A/Chicken/Italy/13474/99 highly pathogenic (HP) AI (HPAI) virus was established. Depending on the vaccination schedule, one or two administrations of 0.5 microg of hemagglutinin protected chickens against clinical signs and death and completely prevented virus shedding from birds challenged at different times after vaccination.

  12. Swine Influenza/Variant Influenza Viruses

    Science.gov (United States)

    ... Address What's this? Submit What's this? Submit Button Influenza Types Seasonal Avian Swine Variant Pandemic Other Information on Swine Influenza/Variant Influenza Virus Language: English (US) Español Recommend ...

  13. Use of a novel virus inactivation method for a multicenter avian influenza real-time reverse transcriptase-polymerase chain reaction proficiency study.

    Science.gov (United States)

    Spackman, Erica; Suarez, David L

    2005-01-01

    Proficiency assessments are important elements in quality control for diagnostic laboratories. Traditionally, proficiency testing for polymerase chain reaction (PCR)-based assays has involved the use of clinical samples, samples "spiked" with live agents or DNA plasmids. Because of government regulations and biosecurity concerns, distribution of live high-consequence pathogens of livestock and poultry, such as avian influenza, is not possible, and DNA plasmids are not technically suitable for evaluating RNA virus detection. Therefore, a proficiency testing panel using whole avian influenza in a diluent containing a phenolic disinfectant that inactivates the virus while preserving the RNA for at least 8 weeks at -70 C was developed and used in a multicenter proficiency assessment for a type A influenza real-time reverse transcriptase (RT)-PCR test. The test, which was highly standardized, except for variation in the real-time RT-PCR equipment used, was shown to be highly reproducible by proficiency testing in 12 laboratories in the United States, Canada, and Hong Kong. Variation in cycle threshold values among 35 data sets and 490 samples was minimal (CV = 5.19%), and sample identifications were highly accurate (96.7% correct identifications) regardless of real-time PCR instrumentation.

  14. Pulmonary immunization of chickens using non-adjuvanted spray-freeze dried whole inactivated virus vaccine completely protects against highly pathogenic H5N1 avian influenza virus

    NARCIS (Netherlands)

    Peeters, Ben; Tonnis, Wouter F.; Murugappan, Senthil; Rottier, Peter; Koch, Guus; Frijlink, Henderik W.; Huckriede, Anke; Hinrichs, Wouter L. J.

    2014-01-01

    Highly pathogenic avian influenza (HPAI) H5N1 virus is a major threat to public health as well as to the global poultry industry. Most fatal human infections are caused by contact with infected poultry. Therefore, preventing the virus from entering the poultry population is a priority. This is,

  15. Avian influenza virus

    Science.gov (United States)

    Avian influenza virus (AIV) is type A influenza that is adapted to avian host species. Although the virus can be isolated from numerous avian species, the natural host reservoir species are dabbling ducks, shorebirds and gulls. Domestic poultry species (poultry being defined as birds that are rais...

  16. Thermal inactivation of H5N2 high-pathogenicity avian influenza virus in dried egg white with 7.5% moisture.

    Science.gov (United States)

    Thomas, Colleen; Swayne, David E

    2009-09-01

    High-pathogenicity avian influenza viruses (HPAIV) cause severe systemic disease with high mortality in chickens. Isolation of HPAIV from the internal contents of chicken eggs has been reported, and this is cause for concern because HPAIV can be spread by movement of poultry products during marketing and trade activity. This study presents thermal inactivation data for the HPAIV strain A/chicken/PA/1370/83 (H5N2) (PA/83) in dried egg white with a moisture content (7.5%) similar to that found in commercially available spray-dried egg white products. The 95% upper confidence limits for D-values calculated from linear regression of the survival curves at 54.4, 60.0, 65.5, and 71.1 degrees C were 475.4, 192.2, 141.0, and 50.1 min, respectively. The line equation y = [0.05494 x degrees C] + 5.5693 (root mean square error = 0.0711) was obtained by linear regression of experimental D-values versus temperature. Conservative predictions based on the thermal inactivation data suggest that standard industry pasteurization protocols would be very effective for HPAIV inactivation in dried egg white. For example, these calculations predict that a 7-log reduction would take only 2.6 days at 54.4 degrees C.

  17. Protective efficacy of an inactivated Eurasian avian-like H1N1 swine influenza vaccine against homologous H1N1 and heterologous H1N1 and H1N2 viruses in mice.

    Science.gov (United States)

    Sui, Jinyu; Yang, Dawei; Qiao, Chuanling; Xu, Huiyang; Xu, Bangfeng; Wu, Yunpu; Yang, Huanliang; Chen, Yan; Chen, Hualan

    2016-07-19

    Eurasian avian-like H1N1 (EA H1N1) swine influenza viruses are prevalent in pigs in Europe and Asia, but occasionally cause human infection, which raises concern about their pandemic potential. Here, we produced a whole-virus inactivated vaccine with an EA H1N1 strain (A/swine/Guangxi/18/2011, SW/GX/18/11) and evaluated its efficacy against homologous H1N1 and heterologous H1N1 and H1N2 influenza viruses in mice. A strong humoral immune response, which we measured by hemagglutination inhibition (HI) and virus neutralization (VN), was induced in the vaccine-inoculated mice upon challenge. The inactivated SW/GX/18/11 vaccine provided complete protection against challenge with homologous SW/GX/18/11 virus in mice and provided effective protection against challenge with heterologous H1N1 and H1N2 viruses with distinctive genomic combinations. Our findings suggest that this EA H1N1 vaccine can provide protection against both homologous H1N1 and heterologous H1N1 or H1N2 virus infection. As such, it is an excellent vaccine candidate to prevent H1N1 swine influenza. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Efficacy of single dose of a bivalent vaccine containing inactivated Newcastle disease virus and reassortant highly pathogenic avian influenza H5N1 virus against lethal HPAI and NDV infection in chickens.

    Directory of Open Access Journals (Sweden)

    Dong-Hun Lee

    Full Text Available Highly pathogenic avian influenza (HPAI and Newcastle disease (ND are 2 devastating diseases of poultry, which cause great economic losses to the poultry industry. In the present study, we developed a bivalent vaccine containing antigens of inactivated ND and reassortant HPAI H5N1 viruses as a candidate poultry vaccine, and we evaluated its immunogenicity and protective efficacy in specific pathogen-free chickens. The 6:2 reassortant H5N1 vaccine strain containing the surface genes of the A/Chicken/Korea/ES/2003(H5N1 virus was successfully generated by reverse genetics. A polybasic cleavage site of the hemagglutinin segment was replaced by a monobasic cleavage site. We characterized the reverse genetics-derived reassortant HPAI H5N1 clade 2.5 vaccine strain by evaluating its growth kinetics in eggs, minimum effective dose in chickens, and cross-clade immunogenicity against HPAI clade 1 and 2. The bivalent vaccine was prepared by emulsifying inactivated ND (La Sota strain and reassortant HPAI viruses with Montanide ISA 70 adjuvant. A single immunization with this vaccine induced high levels of hemagglutination-inhibiting antibody titers and protected chickens against a lethal challenge with the wild-type HPAI and ND viruses. Our results demonstrate that the bivalent, inactivated vaccine developed in this study is a promising approach for the control of both HPAI H5N1 and ND viral infections.

  19. Intradermal immunization with inactivated swine influenza virus and adjuvant polydi(sodium carboxylatoethylphenoxy)phosphazene (PCEP) induced humoral and cell-mediated immunity and reduced lung viral titres in pigs.

    Science.gov (United States)

    Magiri, Royford; Lai, Ken; Chaffey, Alyssa; Zhou, Yan; Pyo, Hyun-Mi; Gerdts, Volker; Wilson, Heather L; Mutwiri, George

    2018-03-14

    Swine influenza virus is endemic worldwide and it is responsible for significant economic losses to the swine industry. A vaccine that stimulates a rapid and long-lasting protective immune response to prevent this infection is highly sought. Poly[di(sodium carboxylatoethylphenoxy)-phosphazene (PCEP) has demonstrated adjuvant activity when formulated as part of multiple vaccines in mice and pigs. In this study we examined the magnitude and type of immune response induced in pigs vaccinated via the intramuscular or intradermal routes with inactivated swine influenza virus (SIV) H1N1 vaccine formulated with PCEP. Intradermal administration of PCEP-adjuvanted inactivated SIV vaccine stimulated significant anti-SIV antibody titres, increased neutralizing antibodies, and significantly reduced lung virus load with limited reduction of gross lung lesions after challenge with virulent H1N1 relative to control animals. These results indicate that PCEP may be effective as a vaccine adjuvant against swine influenza viruses in pigs and should be considered a potential candidate adjuvant for future swine intradermal influenza vaccines. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. Influenza Vaccination Strategies: Comparing Inactivated and Live Attenuated Influenza Vaccines

    Directory of Open Access Journals (Sweden)

    Saranya Sridhar

    2015-04-01

    Full Text Available Influenza is a major respiratory pathogen causing annual outbreaks and occasional pandemics. Influenza vaccination is the major method of prophylaxis. Currently annual influenza vaccination is recommended for groups at high risk of complications from influenza infection such as pregnant women, young children, people with underlying disease and the elderly, along with occupational groups such a healthcare workers and farm workers. There are two main types of vaccines available: the parenteral inactivated influenza vaccine and the intranasal live attenuated influenza vaccine. The inactivated vaccines are licensed from 6 months of age and have been used for more than 50 years with a good safety profile. Inactivated vaccines are standardized according to the presence of the viral major surface glycoprotein hemagglutinin and protection is mediated by the induction of vaccine strain specific antibody responses. In contrast, the live attenuated vaccines are licensed in Europe for children from 2–17 years of age and provide a multifaceted immune response with local and systemic antibody and T cell responses but with no clear correlate of protection. Here we discuss the immunological immune responses elicited by the two vaccines and discuss future work to better define correlates of protection.

  1. Influvac, a trivalent inactivated subunit influenza vaccine.

    Science.gov (United States)

    Zuccotti, Gian Vincenzo; Fabiano, Valentina

    2011-01-01

    Influenza represents a major sanitary and socio-economic burden and vaccination is universally considered the most effective strategy for preventing the disease and its complications. Traditional influenza vaccines have been on the market since the late 1940s, with million of doses administered annually worldwide, and demonstrated a substantial efficacy and safety. The trivalent inactivated subunit vaccine has been available for more than 25 years and has been studied in healthy children, adults and the elderly and in people affected by underlying chronic medical conditions. We describe vaccine technology focusing on subunit vaccine production procedures and mode of action and provide updated information on efficacy and safety available data. A review of efficacy and safety data in healthy subjects and in high risk populations from major sponsor- and investigator-driven studies. The vaccine showed a good immunogenicity and a favorable safety profile in all target groups. In the panorama of actually available influenza vaccines, trivalent inactivated subunit vaccine represents a well-established tool for preventing flu and the associated complications.

  2. Swine influenza virus: zoonotic potential and vaccination strategies for the control of avian and swine influenzas.

    Science.gov (United States)

    Thacker, Eileen; Janke, Bruce

    2008-02-15

    Influenza viruses are able to infect humans, swine, and avian species, and swine have long been considered a potential source of new influenza viruses that can infect humans. Swine have receptors to which both avian and mammalian influenza viruses bind, which increases the potential for viruses to exchange genetic sequences and produce new reassortant viruses in swine. A number of genetically diverse viruses are circulating in swine herds throughout the world and are a major cause of concern to the swine industry. Control of swine influenza is primarily through the vaccination of sows, to protect young pigs through maternally derived antibodies. However, influenza viruses continue to circulate in pigs after the decay of maternal antibodies, providing a continuing source of virus on a herd basis. Measures to control avian influenza in commercial poultry operations are dictated by the virulence of the virus. Detection of a highly pathogenic avian influenza (HPAI) virus results in immediate elimination of the flock. Low-pathogenic avian influenza viruses are controlled through vaccination, which is done primarily in turkey flocks. Maintenance of the current HPAI virus-free status of poultry in the United States is through constant surveillance of poultry flocks. Although current influenza vaccines for poultry and swine are inactivated and adjuvanted, ongoing research into the development of newer vaccines, such as DNA, live-virus, or vectored vaccines, is being done. Control of influenza virus infection in poultry and swine is critical to the reduction of potential cross-species adaptation and spread of influenza viruses, which will minimize the risk of animals being the source of the next pandemic.

  3. Genetic Reassortment Among the Influenza Viruses (Avian Influenza, Human Influenza and Swine Influenza in Pigs

    Directory of Open Access Journals (Sweden)

    Dyah Ayu Hewajuli

    2012-12-01

    Full Text Available Influenza A virus is a hazardous virus and harm to respiratory tract. The virus infect birds, pigs, horses, dogs, mammals and humans. Pigs are important hosts in ecology of the influenza virus because they have two receptors, namely NeuAc 2,3Gal and NeuAc 2,6Gal which make the pigs are sensitive to infection of influenza virus from birds and humans and genetic reassortment can be occurred. Classical swine influenza H1N1 viruses had been circulated in pigs in North America and other countries for 80 years. In 1998, triple reassortant H3N2 swine influenza viruses that contains genes of human influenza A virus (H3N2, swine influenza virus (H1N1 and avian influenza are reported as cause an outbreaks in pigs in North America. Furthermore, the circulation of triple reassortant H3N2 swine influenza virus resulting reassortant H1N1 swine influenza and reassortant H1N2 swine influenza viruses cause infection in humans. Humans who were infected by triple reassortant swine influenza A virus (H1N1 usually made direct contact with pigs. Although without any clinical symptoms, pigs that are infected by triple reassortant swine influenza A (H1N1 can transmit infection to the humans around them. In June 2009, WHO declared that pandemic influenza of reassortant H1N1 influenza A virus (novel H1N1 has reached phase 6. In Indonesia until 2009, there were 1005 people were infected by H1N1 influenza A and 5 of them died. Novel H1N1 and H5N1 viruses have been circulated in humans and pigs in Indonesia. H5N1 reassortant and H1N1 viruses or the seasonal flu may could arise because of genetic reassortment between avian influenza and humans influenza viruses that infect pigs together.

  4. Avian influenza viruses in humans.

    Science.gov (United States)

    Malik Peiris, J S

    2009-04-01

    Past pandemics arose from low pathogenic avian influenza (LPAI) viruses. In more recent times, highly pathogenic avian influenza (HPAI) H5N1, LPAI H9N2 and both HPAI and LPAI H7 viruses have repeatedly caused zoonotic disease in humans. Such infections did not lead to sustained human-to-human transmission. Experimental infection of human volunteers and seroepidemiological studies suggest that avian influenza viruses of other subtypes may also infect humans. Viruses of the H7 subtype appear to have a predilection to cause conjunctivitis and influenza-like illness (ILI), although HPAI H7N7 virus has also caused fatal respiratory disease. Low pathogenic H9N2 viruses have caused mild ILI and its occurrence may be under-recognised for this reason. In contrast, contemporary HPAI H5N1 viruses are exceptional in their virulence for humans and differ from human seasonal influenza viruses in their pathogenesis. Patients have a primary viral pneumonia progressing to acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndrome. Over 380 human cases have been confirmed to date, with an overall case fatality of 63%. The zoonotic transmission of avian influenza is a rare occurrence, butthe greater public health concern is the adaptation of such viruses to efficient human transmission, which could lead to a pandemic. A better understanding of the ecology of avian influenza viruses and the biological determinants of transmissibility and pathogenicity in humans is important for pandemic preparedness.

  5. Intranasal Immunization with Pressure Inactivated Avian Influenza Elicits Cellular and Humoral Responses in Mice.

    Directory of Open Access Journals (Sweden)

    Shana P C Barroso

    Full Text Available Influenza viruses pose a serious global health threat, particularly in light of newly emerging strains, such as the avian influenza H5N1 and H7N9 viruses. Vaccination remains the primary method for preventing acquiring influenza or for avoiding developing serious complications related to the disease. Vaccinations based on inactivated split virus vaccines or on chemically inactivated whole virus have some important drawbacks, including changes in the immunogenic properties of the virus. To induce a greater mucosal immune response, intranasally administered vaccines are highly desired as they not only prevent disease but can also block the infection at its primary site. To avoid these drawbacks, hydrostatic pressure has been used as a potential method for viral inactivation and vaccine production. In this study, we show that hydrostatic pressure inactivates the avian influenza A H3N8 virus, while still maintaining hemagglutinin and neuraminidase functionalities. Challenged vaccinated animals showed no disease signs (ruffled fur, lethargy, weight loss, and huddling. Similarly, these animals showed less Evans Blue dye leakage and lower cell counts in their bronchoalveolar lavage fluid compared with the challenged non-vaccinated group. We found that the whole inactivated particles were capable of generating a neutralizing antibody response in serum, and IgA was also found in nasal mucosa and feces. After the vaccination and challenge we observed Th1/Th2 cytokine secretion with a prevalence of IFN-γ. Our data indicate that the animals present a satisfactory immune response after vaccination and are protected against infection. Our results may pave the way for the development of a novel pressure-based vaccine against influenza virus.

  6. Antibody responses induced by Japanese whole inactivated vaccines against equine influenza virus (H3N8) belonging to Florida sublineage clade2.

    Science.gov (United States)

    Yamanaka, Takashi; Bannai, Hiroshi; Nemoto, Manabu; Tsujimura, Koji; Kondo, Takashi; Matsumura, Tomio

    2011-04-01

    In 2010, the World Organisation for Animal Health recommended the inclusion of a Florida sublineage clade2 strain of equine influenza virus (H3N8), which is represented by A/equine/Richmond/1/07 (Richmond07), in equine influenza vaccines. Here, we evaluate the antigenic differences between Japanese vaccine strains and Richmond07 by performing hemagglutination inhibition (HI) assays. Ferret antiserum raised to A/equine/La Plata/93 (La Plata93), which is a Japanese vaccine strain, reacted with Richmond07 at a similar titer to La Plata93. Moreover, two hundred racehorses exhibited similar geometric mean HI antibody titers against La Plata93 and Richmond07 (73.1 and 80.8, respectively). Therefore, we can expect the antibody induced by the current Japanese vaccines to provide some protection against Richmond07-like viruses.

  7. Inactivation of various influenza strains to model avian influenza (Bird Flu) with various disinfectant chemistries.

    Energy Technology Data Exchange (ETDEWEB)

    Oberst, R. D.; Bieker, Jill Marie; Souza, Caroline Ann

    2005-12-01

    Due to the grave public health implications and economic impact possible with the emergence of the highly pathogenic avian influenza A isolate, H5N1, currently circulating in Asia we have evaluated the efficacy of various disinfectant chemistries against surrogate influenza A strains. Chemistries included in the tests were household bleach, ethanol, Virkon S{reg_sign}, and a modified version of the Sandia National Laboratories developed DF-200 (DF-200d, a diluted version of the standard DF-200 formulation). Validation efforts followed EPA guidelines for evaluating chemical disinfectants against viruses. The efficacy of the various chemistries was determined by infectivity, quantitative RNA, and qualitative protein assays. Additionally, organic challenges using combined poultry feces and litter material were included in the experiments to simulate environments in which decontamination and remediation will likely occur. In all assays, 10% bleach and Sandia DF-200d were the most efficacious treatments against two influenza A isolates (mammalian and avian) as they provided the most rapid and complete inactivation of influenza A viruses.

  8. Protection against H5N1 Highly Pathogenic Avian and Pandemic (H1N1) 2009 Influenza Virus Infection in Cynomolgus Monkeys by an Inactivated H5N1 Whole Particle Vaccine

    Science.gov (United States)

    Nakayama, Misako; Shichinohe, Shintaro; Itoh, Yasushi; Ishigaki, Hirohito; Kitano, Mitsutaka; Arikata, Masahiko; Pham, Van Loi; Ishida, Hideaki; Kitagawa, Naoko; Okamatsu, Masatoshi; Sakoda, Yoshihiro; Ichikawa, Takaya; Tsuchiya, Hideaki; Nakamura, Shinichiro; Le, Quynh Mai; Ito, Mutsumi; Kawaoka, Yoshihiro; Kida, Hiroshi; Ogasawara, Kazumasa

    2013-01-01

    H5N1 highly pathogenic avian influenza virus (HPAIV) infection has been reported in poultry and humans with expanding clade designations. Therefore, a vaccine that induces immunity against a broad spectrum of H5N1 viruses is preferable for pandemic preparedness. We established a second H5N1 vaccine candidate, A/duck/Hokkaido/Vac-3/2007 (Vac-3), in our virus library and examined the efficacy of inactivated whole particles of this strain against two clades of H5N1 HPAIV strains that caused severe morbidity in cynomolgus macaques. Virus propagation in vaccinated macaques infected with either of the H5N1 HPAIV strains was prevented compared with that in unvaccinated macaques. This vaccine also prevented propagation of a pandemic (H1N1) 2009 virus in macaques. In the vaccinated macaques, neutralization activity, which was mainly shown by anti-hemagglutinin antibody, against H5N1 HPAIVs in plasma was detected, but that against H1N1 virus was not detected. However, neuraminidase inhibition activity in plasma and T-lymphocyte responses in lymph nodes against H1N1 virus were detected. Therefore, cross-clade and heterosubtypic protective immunity in macaques consisted of humoral and cellular immunity induced by vaccination with Vac-3. PMID:24376571

  9. Protection against H5N1 highly pathogenic avian and pandemic (H1N1 2009 influenza virus infection in cynomolgus monkeys by an inactivated H5N1 whole particle vaccine.

    Directory of Open Access Journals (Sweden)

    Misako Nakayama

    Full Text Available H5N1 highly pathogenic avian influenza virus (HPAIV infection has been reported in poultry and humans with expanding clade designations. Therefore, a vaccine that induces immunity against a broad spectrum of H5N1 viruses is preferable for pandemic preparedness. We established a second H5N1 vaccine candidate, A/duck/Hokkaido/Vac-3/2007 (Vac-3, in our virus library and examined the efficacy of inactivated whole particles of this strain against two clades of H5N1 HPAIV strains that caused severe morbidity in cynomolgus macaques. Virus propagation in vaccinated macaques infected with either of the H5N1 HPAIV strains was prevented compared with that in unvaccinated macaques. This vaccine also prevented propagation of a pandemic (H1N1 2009 virus in macaques. In the vaccinated macaques, neutralization activity, which was mainly shown by anti-hemagglutinin antibody, against H5N1 HPAIVs in plasma was detected, but that against H1N1 virus was not detected. However, neuraminidase inhibition activity in plasma and T-lymphocyte responses in lymph nodes against H1N1 virus were detected. Therefore, cross-clade and heterosubtypic protective immunity in macaques consisted of humoral and cellular immunity induced by vaccination with Vac-3.

  10. Influenza Virus Infection in Nonhuman Primates

    Science.gov (United States)

    Karlsson, Erik A.; Engel, Gregory A.; Feeroz, M.M.; San, Sorn; Rompis, Aida; Lee, Benjamin P. Y.-H.; Shaw, Eric; Oh, Gunwha; Schillaci, Michael A.; Grant, Richard; Heidrich, John; Schultz-Cherry, Stacey

    2012-01-01

    To determine whether nonhuman primates are infected with influenza viruses in nature, we conducted serologic and swab studies among macaques from several parts of the world. Our detection of influenza virus and antibodies to influenza virus raises questions about the role of nonhuman primates in the ecology of influenza. PMID:23017256

  11. Protective Efficacy of Recombinant Turkey Herpes Virus (rHVT-H5) and Inactivated H5N1 Vaccines in Commercial Mulard Ducks against the Highly Pathogenic Avian Influenza (HPAI) H5N1 Clade 2.2.1 Virus.

    Science.gov (United States)

    Kilany, Walid H; Safwat, Marwa; Mohammed, Samy M; Salim, Abdullah; Fasina, Folorunso Oludayo; Fasanmi, Olubunmi G; Shalaby, Azhar G; Dauphin, Gwenaelle; Hassan, Mohammed K; Lubroth, Juan; Jobre, Yilma M

    2016-01-01

    In Egypt, ducks kept for commercial purposes constitute the second highest poultry population, at 150 million ducks/year. Hence, ducks play an important role in the introduction and transmission of avian influenza (AI) in the Egyptian poultry population. Attempts to control outbreaks include the use of vaccines, which have varying levels of efficacy and failure. To date, the effects of vaccine efficacy has rarely been determined in ducks. In this study, we evaluated the protective efficacy of a live recombinant vector vaccine based on a turkey Herpes Virus (HVT) expressing the H5 gene from a clade 2.2 H5N1 HPAIV strain (A/Swan/Hungary/499/2006) (rHVT-H5) and a bivalent inactivated H5N1 vaccine prepared from clade 2.2.1 and 2.2.1.1 H5N1 seeds in Mulard ducks. A 0.3ml/dose subcutaneous injection of rHVT-H5 vaccine was administered to one-day-old ducklings (D1) and another 0.5ml/dose subcutaneous injection of the inactivated MEFLUVAC was administered at 7 days (D7). Four separate challenge experiments were conducted at Days 21, 28, 35 and 42, in which all the vaccinated ducks were challenged with 106EID50/duck of H5N1 HPAI virus (A/chicken/Egypt/128s/2012(H5N1) (clade 2.2.1) via intranasal inoculation. Maternal-derived antibody regression and post-vaccination antibody immune responses were monitored weekly. Ducks vaccinated at 21, 28, 35 and 42 days with the rHVT-H5 and MEFLUVAC vaccines were protected against mortality (80%, 80%, 90% and 90%) and (50%, 70%, 80% and 90%) respectively, against challenges with the H5N1 HPAI virus. The amount of viral shedding and shedding rates were lower in the rHVT-H5 vaccine groups than in the MEFLUVAC groups only in the first two challenge experiments. However, the non-vaccinated groups shed significantly more of the virus than the vaccinated groups. Both rHVT-H5 and MEFLUVAC provide early protection, and rHVT-H5 vaccine in particular provides protection against HPAI challenge.

  12. Transmission of Influenza A Viruses

    Science.gov (United States)

    Neumann, Gabriele; Kawaoka, Yoshihiro

    2015-01-01

    Influenza A viruses cause respiratory infections that range from asymptomatic to deadly in humans. Widespread outbreaks (pandemics) are attributable to ‘novel’ viruses that possess a viral hemagglutinin (HA) gene to which humans lack immunity. After a pandemic, these novel viruses form stable virus lineages in humans and circulate until they are replaced by other novel viruses. The factors and mechanisms that facilitate virus transmission among hosts and the establishment of novel lineages are not completely understood, but the HA and basic polymerase 2 (PB2) proteins are thought to play essential roles in these processes by enabling avian influenza viruses to infect mammals and replicate efficiently in their new host. Here, we summarize our current knowledge of the contributions of HA, PB2, and other viral components to virus transmission and the formation of new virus lineages. PMID:25812763

  13. Enhanced pneumonia and disease in pigs vaccinated with an inactivated human-like (δ-cluster) H1N2 vaccine and challenged with pandemic 2009 H1N1 influenza virus.

    Science.gov (United States)

    Gauger, Phillip C; Vincent, Amy L; Loving, Crystal L; Lager, Kelly M; Janke, Bruce H; Kehrli, Marcus E; Roth, James A

    2011-03-24

    Influenza is an economically important respiratory disease affecting swine world-wide with potential zoonotic implications. Genetic reassortment and drift has resulted in genetically and antigenically distinct swine influenza viruses (SIVs). Consequently, prevention of SIV infection is challenging due to the increased rate of genetic change and a potential lack of cross-protection between vaccine strains and circulating novel isolates. This report describes a vaccine-heterologous challenge model in which pigs were administered an inactivated H1N2 vaccine with a human-like (δ-cluster) H1 six and three weeks before challenge with H1 homosubtypic, heterologous 2009 pandemic H1N1. At necropsy, macroscopic and microscopic pneumonia scores were significantly higher in the vaccinated and challenged (Vx/Ch) group compared to non-vaccinated and challenged (NVx/Ch) pigs. The Vx/Ch group also demonstrated enhanced clinical disease and a significantly elevated pro-inflammatory cytokine profile in bronchoalveolar lavage fluid compared to the NVx/Ch group. In contrast, viral shedding and replication were significantly higher in NVx/Ch pigs although all challenged pigs, including Vx/Ch pigs, were shedding virus in nasal secretions. Hemagglutination inhibition (HI) and serum neutralizing (SN) antibodies were detected to the priming antigen in the Vx/Ch pigs but no measurable cross-reacting HI or SN antibodies were detected to pandemic H1N1 (pH1N1). Overall, these results suggest that inactivated SIV vaccines may potentiate clinical signs, inflammation and pneumonia following challenge with divergent homosubtypic viruses that do not share cross-reacting HI or SN antibodies. Published by Elsevier Ltd.

  14. Pandemic swine influenza virus: Preparedness planning | Ojogba ...

    African Journals Online (AJOL)

    The novel H1N1 influenza virus that emerged in humans in Mexico in early 2009 and transmitted efficiently in the human population with global spread was declared a pandemic strain. The introduction of different avian and human influenza virus genes into swine influenza viruses often result in viruses of increased fitness ...

  15. Fullerene C60 and graphene photosensibiles for photodynamic virus inactivation

    Science.gov (United States)

    Belousova, I.; Hvorostovsky, A.; Kiselev, V.; Zarubaev, V.; Kiselev, O.; Piotrovsky, L.; Anfimov, P.; Krisko, T.; Muraviova, T.; Rylkov, V.; Starodubzev, A.; Sirotkin, A.; Grishkanich, A.; Kudashev, I.; Kancer, A.; Kustikova, M.; Bykovskaya, E.; Mayurova, A.; Stupnikov, A.; Ruzankina, J.; Afanasyev, M.; Lukyanov, N.; Redka, D.; Paklinov, N.

    2018-02-01

    A solid-phase photosensitizer based on aggregated C60 fullerene and graphene oxide for photodynamic inactivation of pathogens in biological fluids was studied. The most promising technologies of inactivation include the photodynamic effect, which consists in the inactivation of infectious agents by active oxygen forms (including singlet oxygen), formed when light is activated by the photosensitizer introduced into the plasma. Research shows features of solid-phase systems based on graphene and fullerene C60 oxide, which is a combination of an effective inactivating pathogens (for example, influenza viruses) reactive oxygen species formed upon irradiation of the photosensitizer in aqueous and biological fluids, a high photostability fullerene coatings and the possibility of full recovery photosensitizer from the biological environment after the photodynamic action.

  16. Avian Influenza A Virus Infections in Humans

    Science.gov (United States)

    ... people has ranged from mild to severe. Avian Influenza Transmission Avian Influenza Transmission Infographic [555 KB, 2 pages] Spanish [ ... important for public health. Signs and Symptoms of Avian Influenza A Virus Infections in Humans The reported signs ...

  17. Radiobiological inactivation of Epstein-Barr virus

    International Nuclear Information System (INIS)

    Henderson, E.; Heston, L.; Grogan, E.; Miller, G.

    1978-01-01

    Lymphocyte transforming properties of B95-8 strain Epstein-Barr virus (EBV) are very sensitive to inactivation by either uv or x irradiation. No dose of irradiation increases the transforming capacity of EBV. The x-ray dose needed for inactivation of EBV transformation (dose that results in 37% survival, 60,000 rads) is similar to the dose required for inactivation of plaque formation by herpes simplex virus type 1 (Fischer strain). Although herpes simplex virus is more sensitive than EBV to uv irradiation, this difference is most likely due to differences in the kinetics or mechanisms of repair of uv damage to the two viruses. The results lead to the hypothesis that a large part, or perhaps all, of the EBV genome is in some way needed to initiate transformation. The abilities of EBV to stimulate host cell DNA synthesis, to induce nuclear antigen, and to immortalize are inactivated in parallel. All clones of marmoset cells transformed by irradiated virus produce extracellular transforming virus. These findings suggest that the abilities of the virus to transform and to replicate complete progeny are inactivated together. The amounts of uv and x irradiation that inactivate transformation by B95-8 virus are less than the dose needed to inactivate early antigen induction by the nontransforming P 3 HR-1 strain of EBV. Based on radiobiological inactivation, 10 to 50% of the genome is needed for early antigen induction

  18. Photodynamic Inactivation of Mammalian Viruses and Bacteriophages

    Directory of Open Access Journals (Sweden)

    Liliana Costa

    2012-06-01

    Full Text Available Photodynamic inactivation (PDI has been used to inactivate microorganisms through the use of photosensitizers. The inactivation of mammalian viruses and bacteriophages by photosensitization has been applied with success since the first decades of the last century. Due to the fact that mammalian viruses are known to pose a threat to public health and that bacteriophages are frequently used as models of mammalian viruses, it is important to know and understand the mechanisms and photodynamic procedures involved in their photoinactivation. The aim of this review is to (i summarize the main approaches developed until now for the photodynamic inactivation of bacteriophages and mammalian viruses and, (ii discuss and compare the present state of the art of mammalian viruses PDI with phage photoinactivation, with special focus on the most relevant mechanisms, molecular targets and factors affecting the viral inactivation process.

  19. Influenza B viruses : not to be discounted

    NARCIS (Netherlands)

    van de Sandt, Carolien E; Bodewes, Rogier; Rimmelzwaan, Guus F; de Vries, Rory D

    2015-01-01

    In contrast to influenza A viruses, which have been investigated extensively, influenza B viruses have attracted relatively little attention. However, influenza B viruses are an important cause of morbidity and mortality in the human population and full understanding of their biological and

  20. Influenza (flu) vaccine (Inactivated or Recombinant): What you need to know

    Science.gov (United States)

    ... taken in its entirety from the CDC Inactivated Influenza Vaccine Information Statement (VIS) www.cdc.gov/vaccines/hcp/vis/vis-statements/flu.html CDC review information for Inactivated Influenza VIS: ...

  1. Gamma-irradiated influenza A virus can prime for a cross-reactive and cross-protective immune response against influenza A viruses

    International Nuclear Information System (INIS)

    Mullbacher, A.; Ada, G.L.; Tha Hla, R.

    1988-01-01

    A-strain influenza virus A/JAP (H2N2) was tested for its ability to induce cytotoxic T cells (Tc) after being rendered non-infectious by either UV or gamma irradiation. Gamma-irradiated virus proved to be more efficient than UV-inactivated virus in priming for a memory Tc cell response or in boosting memory spleen cells in vitro. Most importantly, γ-inactivated, but not UV-inactivated, A/JAP immunized animals survived lethal challenge with heterologous (A/PC(H3N2), A/WSN(H1N1)) virus as effectively as mice primed with infectious virus

  2. The effect of age and recent influenza vaccination history on the immunogenicity and efficacy of 2009-10 seasonal trivalent inactivated influenza vaccination in children.

    Directory of Open Access Journals (Sweden)

    Sophia Ng

    Full Text Available There is some evidence that annual vaccination of trivalent inactivated influenza vaccine (TIV may lead to reduced vaccine immunogenicity but evidence is lacking on whether vaccine efficacy is affected by prior vaccination history. The efficacy of one dose of TIV in children 6-8 y of age against influenza B is uncertain. We examined whether immunogenicity and efficacy of influenza vaccination in school-age children varied by age and past vaccination history.We conducted a randomized controlled trial of 2009-10 TIV. Influenza vaccination history in the two preceding years was recorded. Immunogenicity was assessed by comparison of HI titers before and one month after receipt of TIV/placebo. Subjects were followed up for 11 months with symptom diaries, and respiratory specimens were collected during acute respiratory illnesses to permit confirmation of influenza virus infections. We found that previous vaccination was associated with reduced antibody responses to TIV against seasonal A(H1N1 and A(H3N2 particularly in children 9-17 y of age, but increased antibody responses to the same lineage of influenza B virus in children 6-8 y of age. Serological responses to the influenza A vaccine viruses were high regardless of vaccination history. One dose of TIV appeared to be efficacious against confirmed influenza B in children 6-8 y of age regardless of vaccination history.Prior vaccination was associated with lower antibody titer rises following vaccination against seasonal influenza A vaccine viruses, but higher responses to influenza B among individuals primed with viruses from the same lineage in preceding years. In a year in which influenza B virus predominated, no impact of prior vaccination history was observed on vaccine efficacy against influenza B. The strains that circulated in the year of study did not allow us to study the effect of prior vaccination on vaccine efficacy against influenza A.

  3. viruses associated with human and animal influenza - a review 40

    African Journals Online (AJOL)

    DR. AMINU

    These include Influenza A,B and C. Influenza viruses are members of the family. Orthomyxoviridae. .... low pathogenicity avian influenza may be as mild as ruffled feathers, a ... influenza A viruses are zoonotic agents recognized as continuing ...

  4. Live Attenuated Versus Inactivated Influenza Vaccine in Hutterite Children: A Cluster Randomized Blinded Trial.

    Science.gov (United States)

    Loeb, Mark; Russell, Margaret L; Manning, Vanessa; Fonseca, Kevin; Earn, David J D; Horsman, Gregory; Chokani, Khami; Vooght, Mark; Babiuk, Lorne; Schwartz, Lisa; Neupane, Binod; Singh, Pardeep; Walter, Stephen D; Pullenayegum, Eleanor

    2016-11-01

    Whether vaccinating children with intranasal live attenuated influenza vaccine (LAIV) is more effective than inactivated influenza vaccine (IIV) in providing both direct protection in vaccinated persons and herd protection in unvaccinated persons is uncertain. Hutterite colonies, where members live in close-knit, small rural communities in which influenza virus infection regularly occurs, offer an opportunity to address this question. To determine whether vaccinating children and adolescents with LAIV provides better community protection than IIV. A cluster randomized blinded trial conducted between October 2012 and May 2015 over 3 influenza seasons. (ClinicalTrials.gov: NCT01653015). 52 Hutterite colonies in Alberta and Saskatchewan, Canada. 1186 Canadian children and adolescents aged 36 months to 15 years who received the study vaccine and 3425 community members who did not. Children were randomly assigned according to community in a blinded manner to receive standard dosing of either trivalent LAIV or trivalent IIV. The primary outcome was reverse transcriptase polymerase chain reaction-confirmed influenza A or B virus in all participants (vaccinated children and persons who did not receive the study vaccine). Mean vaccine coverage among children in the LAIV group was 76.9% versus 72.3% in the IIV group. Influenza virus infection occurred at a rate of 5.3% (295 of 5560 person-years) in the LAIV group versus 5.2% (304 of 5810 person-years) in the IIV group. The hazard ratio comparing LAIV with IIV for influenza A or B virus was 1.03 (95% CI, 0.85 to 1.24). The study was conducted in Hutterite communities, which may limit generalizability. Immunizing children with LAIV does not provide better community protection against influenza than IIV. The Canadian Institutes for Health Research.

  5. Emerging influenza virus: A global threat

    Indian Academy of Sciences (India)

    PRAKASH KUMAR

    Emerging influenza virus: A global threat. 475. J. Biosci. ... pathogens and are of major global health concern. Recently, ..... cases among persons in 14 countries in Asia, the Middle ... of influenza, investment in pandemic vaccine research and.

  6. Enhanced pulmonary immunization with aerosolized inactivated influenza vaccine containing delta inulin adjuvant.

    Science.gov (United States)

    Murugappan, Senthil; Frijlink, Henderik W; Petrovsky, Nikolai; Hinrichs, Wouter L J

    2015-01-23

    Vaccination is the primary intervention to contain influenza virus spread during seasonal and pandemic outbreaks. Pulmonary vaccination is gaining increasing attention for its ability to induce both local mucosal and systemic immune responses without the need for invasive injections. However, pulmonary administration of whole inactivated influenza virus (WIV) vaccine induces a Th2 dominant systemic immune response while a more balanced Th1/Th2 vaccine response may be preferred and only induces modest nasal immunity. This study evaluated immunity elicited by pulmonary versus intramuscular (i.m.) delivery of WIV, and tested whether the immune response could be improved by co-administration of delta (δ)-inulin, a novel carbohydrate-based particulate adjuvant. After pulmonary administration both unadjuvanted and δ-inulin adjuvanted WIV induced a potent systemic immune response, inducing higher serum anti-influenza IgG titers and nasal IgA titers than i.m. administration. Moreover, the addition of δ-inulin induced a more balanced Th1/Th2 response and induced higher nasal IgA titers versus pulmonary WIV alone. Pulmonary WIV alone or with δ-inulin induced hemagglutination inhibition (HI) titers>40, titers which are considered protective against influenza virus. In conclusion, in this study we have shown that δ-inulin adjuvanted WIV induces a better immune response after pulmonary administration than vaccine alone. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Effect of Osmotic Pressure on the Stability of Whole Inactivated Influenza Vaccine for Coating on Microneedles.

    Directory of Open Access Journals (Sweden)

    Hyo-Jick Choi

    Full Text Available Enveloped virus vaccines can be damaged by high osmotic strength solutions, such as those used to protect the vaccine antigen during drying, which contain high concentrations of sugars. We therefore studied shrinkage and activity loss of whole inactivated influenza virus in hyperosmotic solutions and used those findings to improve vaccine coating of microneedle patches for influenza vaccination. Using stopped-flow light scattering analysis, we found that the virus underwent an initial shrinkage on the order of 10% by volume within 5 s upon exposure to a hyperosmotic stress difference of 217 milliosmolarity. During this shrinkage, the virus envelope had very low osmotic water permeability (1 - 6×10-4 cm s-1 and high Arrhenius activation energy (Ea = 15.0 kcal mol-1, indicating that the water molecules diffused through the viral lipid membranes. After a quasi-stable state of approximately 20 s to 2 min, depending on the species and hypertonic osmotic strength difference of disaccharides, there was a second phase of viral shrinkage. At the highest osmotic strengths, this led to an undulating light scattering profile that appeared to be related to perturbation of the viral envelope resulting in loss of virus activity, as determined by in vitro hemagglutination measurements and in vivo immunogenicity studies in mice. Addition of carboxymethyl cellulose effectively prevented vaccine activity loss in vitro and in vivo, believed to be due to increasing the viscosity of concentrated sugar solution and thereby reducing osmotic stress during coating of microneedles. These results suggest that hyperosmotic solutions can cause biphasic shrinkage of whole inactivated influenza virus which can damage vaccine activity at high osmotic strength and that addition of a viscosity enhancer to the vaccine coating solution can prevent osmotically driven damage and thereby enable preparation of stable microneedle coating formulations for vaccination.

  8. Virulence determinants of pandemic influenza viruses

    Science.gov (United States)

    Tscherne, Donna M.; García-Sastre, Adolfo

    2011-01-01

    Influenza A viruses cause recurrent, seasonal epidemics and occasional global pandemics with devastating levels of morbidity and mortality. The ability of influenza A viruses to adapt to various hosts and undergo reassortment events ensures constant generation of new strains with unpredictable degrees of pathogenicity, transmissibility, and pandemic potential. Currently, the combination of factors that drives the emergence of pandemic influenza is unclear, making it impossible to foresee the details of a future outbreak. Identification and characterization of influenza A virus virulence determinants may provide insight into genotypic signatures of pathogenicity as well as a more thorough understanding of the factors that give rise to pandemics. PMID:21206092

  9. Avian influenza virus transmission to mammals.

    Science.gov (United States)

    Herfst, S; Imai, M; Kawaoka, Y; Fouchier, R A M

    2014-01-01

    Influenza A viruses cause yearly epidemics and occasional pandemics. In addition, zoonotic influenza A viruses sporadically infect humans and may cause severe respiratory disease and fatalities. Fortunately, most of these viruses do not have the ability to be efficiently spread among humans via aerosols or respiratory droplets (airborne transmission) and to subsequently cause a pandemic. However, adaptation of these zoonotic viruses to humans by mutation or reassortment with human influenza A viruses may result in airborne transmissible viruses with pandemic potential. Although our knowledge of factors that affect mammalian adaptation and transmissibility of influenza viruses is still limited, we are beginning to understand some of the biological traits that drive airborne transmission of influenza viruses among mammals. Increased understanding of the determinants and mechanisms of airborne transmission may aid in assessing the risks posed by avian influenza viruses to human health, and preparedness for such risks. This chapter summarizes recent discoveries on the genetic and phenotypic traits required for avian influenza viruses to become airborne transmissible between mammals.

  10. A randomized clinical trial of an inactivated avian influenza A (H7N7 vaccine.

    Directory of Open Access Journals (Sweden)

    Robert B Couch

    Full Text Available BACKGROUND: Concern for a pandemic caused by a newly emerged avian influenza A virus has led to clinical trials with candidate vaccines as preparation for such an event. Most trials have involved vaccines for influenza A (H5N1, A (H7N7 or A (H9N2. OBJECTIVE: To evaluate dosage-related safety and immunogenicity of an inactivated influenza A (H7N7 vaccine in humans. DESIGN: One hundred twenty-five healthy young adults were randomized to receive two doses intramuscularly of placebo or 7.5, 15, 45 or 90 µg of HA of an inactivated subunit influenza A (H7N7 vaccine (25 per group, four weeks apart. Reactogenicity was evaluated closely for one week and for any adverse effect for six months after each dose. Serum hemagglutination-inhibiting and neutralizing antibody responses were determined four weeks after each dose and at six months. RESULTS: Reactogenicity evaluations indicated the vaccinations were well tolerated. Only one subject developed a ≥4-fold serum hemagglutination-inhibition (HAI antibody response and a final titer of ≥1:40 four weeks after dose two and only five subjects developed a neutralizing antibody rise and a final titer of ≥1:40 in tests performed at a central laboratory. Four of the five were given the 45 or 90 µg HA dosage. A more sensitive HAI assay at the study site revealed a dose-response with increasing HA dosage but only 36% in the 90 µg HA group developed a ≥4-fold rise in antibody in this test and only one of these achieved a titer of ≥1:32. CONCLUSION: This inactivated subunit influenza A (H7N7 vaccine was safe but poorly immunogenic in humans. TRIALS REGISTRATION: ClinicalTrials.gov NCT00546585.

  11. Enhanced Stability of Inactivated Influenza Vaccine Encapsulated in Dissolving Microneedle Patches.

    Science.gov (United States)

    Chu, Leonard Y; Ye, Ling; Dong, Ke; Compans, Richard W; Yang, Chinglai; Prausnitz, Mark R

    2016-04-01

    This study tested the hypothesis that encapsulation of influenza vaccine in microneedle patches increases vaccine stability during storage at elevated temperature. Whole inactivated influenza virus vaccine (A/Puerto Rico/8/34) was formulated into dissolving microneedle patches and vaccine stability was evaluated by in vitro and in vivo assays of antigenicity and immunogenicity after storage for up to 3 months at 4, 25, 37 and 45°C. While liquid vaccine completely lost potency as determined by hemagglutination (HA) activity within 1-2 weeks outside of refrigeration, vaccine in microneedle patches lost 40-50% HA activity during or shortly after fabrication, but then had no significant additional loss of activity over 3 months of storage, independent of temperature. This level of stability required reduced humidity by packaging with desiccant, but was not affected by presence of oxygen. This finding was consistent with additional stability assays, including antigenicity of the vaccine measured by ELISA, virus particle morphological structure captured by transmission electron microscopy and protective immune responses by immunization of mice in vivo. These data show that inactivated influenza vaccine encapsulated in dissolving microneedle patches has enhanced stability during extended storage at elevated temperatures.

  12. [An overview on swine influenza viruses].

    Science.gov (United States)

    Yang, Shuai; Zhu, Wen-Fei; Shu, Yue-Long

    2013-05-01

    Swine influenza viruses (SIVs) are respiratory pathogens of pigs. They cause both economic bur den in livestock-dependent industries and serious global public health concerns in humans. Because of their dual susceptibility to human and avian influenza viruses, pigs are recognized as intermediate hosts for genetic reassortment and interspecies transmission. Subtypes H1N1, H1N2, and H3N2 circulate in swine populations around the world, with varied origin and genetic characteristics among different continents and regions. In this review, the role of pigs in evolution of influenza A viruses, the genetic evolution of SIVs and interspecies transmission of SIVs are described. Considering the possibility that pigs might produce novel influenza viruses causing more outbreaks and pandemics, routine epidemiological surveillance of influenza viruses in pig populations is highly recommended.

  13. Isolation of avian influenza virus in Texas.

    Science.gov (United States)

    Glass, S E; Naqi, S A; Grumbles, L C

    1981-01-01

    An avian influenza virus with surface antigens similar to those of fowl plague virus (Hav 1 Nav 2) was isolated in 1979 from 2 commercial turkey flocks in Central Texas. Two flocks in contact with these infected flocks developed clinical signs, gross lesions, and seroconversion but yielded no virus. This was the first recorded incidence of clinical avian influenza in Texas turkeys and only the second time that an agent with these surface antigens was isolated from turkeys in U.S.

  14. Immunogenicity of UV-inactivated measles virus

    International Nuclear Information System (INIS)

    Zahorska, R.; Mazur, N.; Korbecki, M.

    1978-01-01

    By means of the antigen extinction limit test it was shown that a triple dose vaccination of guinea pigs with UV-inactivated measles virus gave better results, than a single dose vaccination which was proved by the very low immunogenicity index. For both vaccination schemes (single and triple) the immune response was only sligthly influenced by a change of dose from 10 5 to 10 6 HadU 50 /ml or by the addition of aluminum adjuvant. In the antigen extinction limit test the antibody levels were determined by two methods (HIT and NT) the results of which were statistically equivalent. The UV-inactivated measles virus was also found to induce hemolysis-inhibiting antibodies. (orig.) [de

  15. SAFETY AND EFFICIENCY OF INACTIVATED OF SUBUNIT INFLUENZA VACCINE AT MASS VACCINATION OF CHILDREN

    Directory of Open Access Journals (Sweden)

    Yu.Z. Gendon

    2007-01-01

    Full Text Available The article considers the results of infantile mass vaccination with inactivated subunit influenza vaccine (Influvac. It shows that vaccination of 57–72% of children aged 3–17 from organized collectives residing in Mytishchi and Orekhovoczuevo districts of Moscow region was accompanied with nearly triple reduce of flu rates vs. Narofominsk and Odintsovo districts where vaccination was occasional (< 1% of children. The efficiency of the vaccination made 63,7%. Low reactogenicity of the influenza vaccine was recorded. Its convenient packing allows vaccination of large number of children in a short time. The article justifies the necessity of yearly vaccinations even in case of similarity of flu virus strain.Key words: children, mass vaccination, subunit flu vaccine, safety.

  16. Viruses associated with human and animal influenza - a review ...

    African Journals Online (AJOL)

    In this review, the most important viruses associated with human and animal influenza are reported. These include Influenza A,B and C. Influenza viruses are members of the family Orthomyxoviridae. Influenza A virus being the most pathogenic and wide spread with many subtypes has constantly cause epidemics in several ...

  17. Emerging influenza viruses and the prospect of a universal influenza virus vaccine.

    Science.gov (United States)

    Krammer, Florian

    2015-05-01

    Influenza viruses cause annual seasonal epidemics and pandemics at irregular intervals. Several cases of human infections with avian and swine influenza viruses have been detected recently, warranting enhanced surveillance and the development of more effective countermeasures to address the pandemic potential of these viruses. The most effective countermeasure against influenza virus infection is the use of prophylactic vaccines. However, vaccines that are currently in use for seasonal influenza viruses have to be re-formulated and re-administered in a cumbersome process every year due to the antigenic drift of the virus. Furthermore, current seasonal vaccines are ineffective against novel pandemic strains. This paper reviews zoonotic influenza viruses with pandemic potential and technological advances towards better vaccines that induce broad and long lasting protection from influenza virus infection. Recent efforts have focused on the development of broadly protective/universal influenza virus vaccines that can provide immunity against drifted seasonal influenza virus strains but also against potential pandemic viruses. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Screening for influenza viruses in 7804 patients with influenza-like symptoms

    International Nuclear Information System (INIS)

    Xuehui Li; Nan Lv; Chen Hangwe; Lanhua You; Huimin Wang

    2010-01-01

    To screen a large number of patients with influenza-like symptoms by using the gold-immunochromatographic assay kit. All patients with influenza-like symptoms visiting the outpatient department of the General Hospital of Beijing Military Region, Beijing, China between May 2009 and January 2010 were enrolled in the study. Nasopharyngeal swabs were collected immediately after the patient visited, then a gold-immunochromatographic assay was performed for screening of influenza A and B viruses according to the kit protocol. Among the 7804 patients enrolled in this study, 202 patients were influenza virus-positive; the positive cases accounted for 2.6% of all cases detected. Among the 202 influenza virus-positive patients, 171 patients were influenza virus A-positive, 24 were influenza virus B-positive, and 7 were co-infected with influenza virus A and B. More than 57% of the virus-positive patients were younger than 30 years old. Symptoms such as fever, sore throat, nasal congestion, sneezing, runny nose, and joint pain were more frequently observed in influenza virus A-positive patients than in influenza virus B-positive and influenza virus-negative patients. The gold immunochromatographic assay kit is very useful for screening a large number of patients with influenza-like symptoms. A higher number of influenza virus A-positive patients have sore throat, nasal congestion, sneezing, runny nose, and joint pain than influenza virus B-positive and influenza virus-negative patients (Author).

  19. History of Swine influenza viruses in Asia.

    Science.gov (United States)

    Zhu, Huachen; Webby, Richard; Lam, Tommy T Y; Smith, David K; Peiris, Joseph S M; Guan, Yi

    2013-01-01

    The pig is one of the main hosts of influenza A viruses and plays important roles in shaping the current influenza ecology. The occurrence of the 2009 H1N1 pandemic influenza virus demonstrated that pigs could independently facilitate the genesis of a pandemic influenza strain. Genetic analyses revealed that this virus was derived by reassortment between at least two parent swine influenza viruses (SIV), from the northern American triple reassortant H1N2 (TR) and European avian-like H1N1 (EA) lineages. The movement of live pigs between different continents and subsequent virus establishment are preconditions for such a reassortment event to occur. Asia, especially China, has the largest human and pig populations in the world, and seems to be the only region frequently importing pigs from other continents. Virological surveillance revealed that not only classical swine H1N1 (CS), and human-origin H3N2 viruses circulated, but all of the EA, TR and their reassortant variants were introduced into and co-circulated in pigs in this region. Understanding the long-term evolution and history of SIV in Asia would provide insights into the emergence of influenza viruses with epidemic potential in swine and humans.

  20. Ebola Virus Inactivation by Detergents Is Annulled in Serum

    NARCIS (Netherlands)

    van Kampen, Jeroen J. A.; Tintu, Andrei; Russcher, Henk; Fraaij, Pieter L. A.; Reusken, Chantal B. E. M.; Rijken, Mikel; van Hellemond, Jaap J.; van Genderen, Perry J. J.; Koelewijn, Rob; de Jong, Menno D.; Haddock, Elaine; Fischer, Robert J.; Munster, Vincent J.; Koopmans, Marion P. G.

    2017-01-01

    Treatment of blood samples from hemorrhagic fever virus (HFV)-infected patients with 0.1% detergents has been recommended for virus inactivation and subsequent safe laboratory testing. However, data on virus inactivation by this procedure are lacking. Here we show the effect of this procedure on

  1. Inactivation of RNA viruses by gamma irradiation

    International Nuclear Information System (INIS)

    Nonomiya, Takashi; Morimoto, Akinori; Iwatsuki, Kazuo; Tsutsumi, Takamasa; Ito, Hitoshi; Yamashiro, Tomio; Ishigaki, Isao.

    1992-01-01

    Four kinds of RNA viruses, Bluetongue virus (BT), Bovine Virus Diarrhea-Mucosal Disease virus (BVD·MD), Bovine Respiratory Syncytial virus (RS), Vesicular Stmatitis virus (VS), were subjected to various doses of gamma irradiation to determine the lethal doses. The D 10 values, which are the dose necessary to decimally reduce infectivity, ranged from 1.5 to 3.4 kGy under frozen condition at dry-ice temperature, and they increased to 2.6 to 5.0 kGy under frozen condition at dry-ice temperature. Serum neutralzing antibody titer of Infectious Bovine Rhinotracheitis (IBR) was not adversely changed by the exposure to 36 kGy of gamma-rays under frozen condition. Analysis of electrophoresis patterns of the bovine serum also reveales that the serum proteins were not remarkably affected, even when exposed to 36 kGy of gamma radiation under frozen condition. The results suggested that gamma irradiation under frozen condition is an effective means for inactivating both DNA and RNA viruses without adversely affecting serum proteins and neutralizing antibody titer. (author)

  2. Inactivation of RNA viruses by gamma irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Nonomiya, Takashi; Morimoto, Akinori; Iwatsuki, Kazuo; Tsutsumi, Takamasa (Ministry of Agriculture, Forestry and fisheries, Yokohama, Kanagawa (Japan). Animal Quarantine Service); Ito, Hitoshi; Yamashiro, Tomio; Ishigaki, Isao

    1992-09-01

    Four kinds of RNA viruses, Bluetongue virus (BT), Bovine Virus Diarrhea-Mucosal Disease virus (BVD[center dot]MD), Bovine Respiratory Syncytial virus (RS), Vesicular Stmatitis virus (VS), were subjected to various doses of gamma irradiation to determine the lethal doses. The D[sub 10] values, which are the dose necessary to decimally reduce infectivity, ranged from 1.5 to 3.4 kGy under frozen condition at dry-ice temperature, and they increased to 2.6 to 5.0 kGy under frozen condition at dry-ice temperature. Serum neutralzing antibody titer of Infectious Bovine Rhinotracheitis (IBR) was not adversely changed by the exposure to 36 kGy of gamma-rays under frozen condition. Analysis of electrophoresis patterns of the bovine serum also reveales that the serum proteins were not remarkably affected, even when exposed to 36 kGy of gamma radiation under frozen condition. The results suggested that gamma irradiation under frozen condition is an effective means for inactivating both DNA and RNA viruses without adversely affecting serum proteins and neutralizing antibody titer. (author).

  3. [Contemporary threat of influenza virus infection].

    Science.gov (United States)

    Płusa, Tadeusz

    2010-01-01

    Swine-origine H1N1 influenza virus (S-OIV) caused a great mobilization of health medical service over the world. Now it is well known that a vaccine against novel virus is expected as a key point in that battle. In the situation when recommended treatment with neuraminidase inhibitors is not sufficient to control influenza A/H1N1 viral infection the quick and precisely diagnostic procedures should be applied to save and protect our patients.

  4. Contribution of murine innate serum inhibitors toward interference within influenza virus immune assays.

    Science.gov (United States)

    Cwach, Kevin T; Sandbulte, Heather R; Klonoski, Joshua M; Huber, Victor C

    2012-03-01

    Prior to detection of an antibody response toward influenza viruses using the hemagglutination inhibition assay (HAI), sera are routinely treated to inactivate innate inhibitors using both heat inactivation (56°C) and recombinant neuraminidase [receptor-destroying enzyme (RDE)]. We revisited the contributions of innate serum inhibitors toward interference with influenza viruses in immune assays, using murine sera, with emphasis on the interactions with influenza A viruses of the H3N2 subtype. We used individual serum treatments: 56°C alone, RDE alone, or RDE + 56°C, to treat sera prior to evaluation within HAI, microneutralization, and macrophage uptake assays. Our data demonstrate that inhibitors present within untreated murine sera interfere with the HAI assay in a manner that is different from that seen for the microneutralization assay. Specifically, the γ class inhibitor α(2) -Macroglobulin (A2-M) can inhibit H3N2 viruses within the HAI assay, but not in the microneutralization assay. Based on these findings, we used a macrophage uptake assay to demonstrate that these inhibitors can increase uptake by macrophages when the influenza viruses express an HA from a 1968 H3N2 virus isolate, but not a 1997 H3N2 isolate. The practice of treating sera to inactivate innate inhibitors of influenza viruses prior to evaluation within immune assays has allowed us to effectively detect influenza virus-specific antibodies for decades. However, this practice has yielded an under-appreciation for the contribution of innate serum inhibitors toward host immune responses against these viruses, including contributions toward neutralization and macrophage uptake. © 2011 Blackwell Publishing Ltd.

  5. Kaempferol ameliorates H9N2 swine influenza virus-induced acute lung injury by inactivation of TLR4/MyD88-mediated NF-κB and MAPK signaling pathways.

    Science.gov (United States)

    Zhang, Ruihua; Ai, Xia; Duan, Yongjie; Xue, Man; He, Wenxiao; Wang, Cunlian; Xu, Tong; Xu, Mingju; Liu, Baojian; Li, Chunhong; Wang, Zhijun; Zhang, Ruihong; Wang, Guohua; Tian, Shufei; Liu, Huifeng

    2017-05-01

    Kaempferol, a very common type of dietary flavonoids, has been found to exert antioxidative and anti-inflammatory properties. The purpose of our investigation was designed to reveal the effect of kaempferol on H9N2 influenza virus-induced inflammation in vivo and in vitro. In vivo, BALB/C mice were infected intranasally with H9N2 influenza virus with or without kaempferol treatment to induce acute lung injury (ALI) model. In vitro, MH-S cells were infected with H9N2 influenza virus with or without kaempferol treatment. In vivo, kaempferol treatment attenuated pulmonary edema, the W/D mass ratio, pulmonary capillary permeability, myeloperoxidase (MPO) activity, and the numbers of inflammatory cells. Kaempferol reduced ROS and Malondialdehyde (MDA) production, and increased the superoxide dismutase (SOD) activity. Kaempferol also reduced overproduction of TNF-α, IL-1β and IL-6. In addition, kaempferol decreased the H9N2 viral titre. In vitro, ROS, MDA, TNF-α, IL-1β and IL-6 was also reduced by kaempferol. Moreover, our data showed that kaempferol significantly inhibited the upregulation of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), phosphorylation level of IκBα and nuclear factor-κB (NF-κB) p65, NF-κB p65 DNA binding activity, and phosphorylation level of MAPKs, both in vivo and in vitro. These results suggest that kaempferol exhibits a protective effect on H9N2 virus-induced inflammation via suppression of TLR4/MyD88-mediated NF-κB and MAPKs pathways, and kaempferol may be considered as an effective drug for the potential treatment of influenza virus-induced ALI. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  6. Vero cell technology for rapid development of inactivated whole virus vaccines for emerging viral diseases.

    Science.gov (United States)

    Barrett, P Noel; Terpening, Sara J; Snow, Doris; Cobb, Ronald R; Kistner, Otfried

    2017-09-01

    Rapid development and production of vaccines against emerging diseases requires well established, validated, robust technologies to allow industrial scale production and accelerated licensure of products. Areas covered: A versatile Vero cell platform has been developed and utilized to deliver a wide range of candidate and licensed vaccines against emerging viral diseases. This platform builds on the 35 years' experience and safety record with inactivated whole virus vaccines such as polio vaccine. The current platform has been optimized to include a novel double inactivation procedure in order to ensure a highly robust inactivation procedure for novel emerging viruses. The utility of this platform in rapidly developing inactivated whole virus vaccines against pandemic (-like) influenza viruses and other emerging viruses such as West Nile, Chikungunya, Ross River and SARS is reviewed. The potential of the platform for development of vaccines against other emerging viruses such as Zika virus is described. Expert commentary: Use of this platform can substantially accelerate process development and facilitate licensure because of the substantial existing data set available for the cell matrix. However, programs to provide vaccines against emerging diseases must allow alternative clinical development paths to licensure, without the requirement to carry out large scale field efficacy studies.

  7. Potent peptidic fusion inhibitors of influenza virus

    Energy Technology Data Exchange (ETDEWEB)

    Kadam, Rameshwar U.; Juraszek, Jarek; Brandenburg, Boerries; Buyck, Christophe; Schepens, Wim B. G.; Kesteleyn, Bart; Stoops, Bart; Vreeken, Rob J.; Vermond, Jan; Goutier, Wouter; Tang, Chan; Vogels, Ronald; Friesen, Robert H. E.; Goudsmit, Jaap; van Dongen, Maria J. P.; Wilson, Ian A.

    2017-09-28

    Influenza therapeutics with new targets and mechanisms of action are urgently needed to combat potential pandemics, emerging viruses, and constantly mutating strains in circulation. We report here on the design and structural characterization of potent peptidic inhibitors of influenza hemagglutinin. The peptide design was based on complementarity-determining region loops of human broadly neutralizing antibodies against the hemagglutinin (FI6v3 and CR9114). The optimized peptides exhibit nanomolar affinity and neutralization against influenza A group 1 viruses, including the 2009 H1N1 pandemic and avian H5N1 strains. The peptide inhibitors bind to the highly conserved stem epitope and block the low pH–induced conformational rearrangements associated with membrane fusion. These peptidic compounds and their advantageous biological properties should accelerate the development of new small molecule– and peptide-based therapeutics against influenza virus.

  8. Silent spread of highly pathogenic Avian Influenza H5N1 virus amongst vaccinated commercial layers

    NARCIS (Netherlands)

    Poetri, O.N.; Boven, M.; Claassen, I.J.T.M.; Koch, G.; Wibawan, I.W.; Stegeman, A.; Broek, van den J.; Bouma, A.

    2014-01-01

    The aim of this study was to determine whether a single vaccination of commercial layer type chickens with an inactivated vaccine containing highly pathogenic avian influenza virus strain H5N1 A/chicken/Legok/2003, carried out on the farm, was sufficient to protect against infection with the

  9. Influenza A (H3N2) Variant Virus

    Science.gov (United States)

    ... Swine Variant Pandemic Other Influenza A (H3N2) Variant Virus Language: English (US) Español Recommend on Facebook Tweet Share Compartir Influenza viruses that normally circulate in pigs are called “variant” ...

  10. Influenza vaccine effectiveness for hospital and community patients using control groups with and without non-influenza respiratory viruses detected, Auckland, New Zealand 2014.

    Science.gov (United States)

    Pierse, Nevil; Kelly, Heath; Thompson, Mark G; Bissielo, Ange; Radke, Sarah; Huang, Q Sue; Baker, Michael G; Turner, Nikki

    2016-01-20

    We aimed to estimate the protection afforded by inactivated influenza vaccine, in both community and hospital settings, in a well characterised urban population in Auckland during 2014. We used two different comparison groups, all patients who tested negative for influenza and only those patients who tested negative for influenza and had a non-influenza respiratory virus detected, to calculate the vaccine effectiveness in a test negative study design. Estimates were made separately for general practice outpatient consultations and hospitalised patients, stratified by age group and by influenza type and subtype. Vaccine status was confirmed by electronic record for general practice patients and all respiratory viruses were detected by real time polymerase chain reaction. 1039 hospitalised and 1154 general practice outpatient consultations met all the study inclusion criteria and had a respiratory sample tested for influenza and other respiratory viruses. Compared to general practice patients, hospitalised patients were more likely to be very young or very old, to be Māori or Pacific Islander, to have a low income and to suffer from chronic disease. Vaccine effectiveness (VE) adjusted for age and other participant characteristics using all influenza negative controls was 42% (95% CI: 16 to 60%) for hospitalised and 56% (95% CI: 35 to 70%) for general practice patients. The vaccine appeared to be most effective against the influenza A(H1N1)pdm09 strain with an adjusted VE of 62% (95% CI:38 to 77%) for hospitalised and 59% (95% CI:36 to 74%) for general practice patients, using influenza virus negative controls. Similar results found when patients testing positive for a non-influenza respiratory virus were used as the control group. This study contributes to validation of the test negative design and confirms that inactivated influenza vaccines continue to provide modest but significant protection against laboratory-confirmed influenza. Copyright © 2015 Elsevier Ltd

  11. Recombinant IgA Is Sufficient To Prevent Influenza Virus Transmission in Guinea Pigs

    Science.gov (United States)

    Seibert, Christopher W.; Rahmat, Saad; Krause, Jens C.; Eggink, Dirk; Albrecht, Randy A.; Goff, Peter H.; Krammer, Florian; Duty, J. Andrew; Bouvier, Nicole M.; García-Sastre, Adolfo

    2013-01-01

    A serum hemagglutination inhibition (HAI) titer of 40 or greater is thought to be associated with reduced influenza virus pathogenesis in humans and is often used as a correlate of protection in influenza vaccine studies. We have previously demonstrated that intramuscular vaccination of guinea pigs with inactivated influenza virus generates HAI titers greater than 300 but does not protect vaccinated animals from becoming infected with influenza virus by transmission from an infected cage mate. Only guinea pigs intranasally inoculated with a live influenza virus or a live attenuated virus vaccine, prior to challenge, were protected from transmission (A. C. Lowen et al., J. Virol. 83:2803–2818, 2009.). Because the serum HAI titer is mostly determined by IgG content, these results led us to speculate that prevention of viral transmission may require IgA antibodies or cellular immune responses. To evaluate this hypothesis, guinea pigs and ferrets were administered a potent, neutralizing mouse IgG monoclonal antibody, 30D1 (Ms 30D1 IgG), against the A/California/04/2009 (H1N1) virus hemagglutinin and exposed to respiratory droplets from animals infected with this virus. Even though HAI titers were greater than 160 1 day postadministration, Ms 30D1 IgG did not prevent airborne transmission to passively immunized recipient animals. In contrast, intramuscular administration of recombinant 30D1 IgA (Ms 30D1 IgA) prevented transmission to 88% of recipient guinea pigs, and Ms 30D1 IgA was detected in animal nasal washes. Ms 30D1 IgG administered intranasally also prevented transmission, suggesting the importance of mucosal immunity in preventing influenza virus transmission. Collectively, our data indicate that IgG antibodies may prevent pathogenesis associated with influenza virus infection but do not protect from virus infection by airborne transmission, while IgA antibodies are more important for preventing transmission of influenza viruses. PMID:23698296

  12. Survival of influenza virus on banknotes.

    Science.gov (United States)

    Thomas, Yves; Vogel, Guido; Wunderli, Werner; Suter, Patricia; Witschi, Mark; Koch, Daniel; Tapparel, Caroline; Kaiser, Laurent

    2008-05-01

    Successful control of a viral disease requires knowledge of the different vectors that could promote its transmission among hosts. We assessed the survival of human influenza viruses on banknotes given that billions of these notes are exchanged daily worldwide. Banknotes were experimentally contaminated with representative influenza virus subtypes at various concentrations, and survival was tested after different time periods. Influenza A viruses tested by cell culture survived up to 3 days when they were inoculated at high concentrations. The same inoculum in the presence of respiratory mucus showed a striking increase in survival time (up to 17 days). Similarly, B/Hong Kong/335/2001 virus was still infectious after 1 day when it was mixed with respiratory mucus. When nasopharyngeal secretions of naturally infected children were used, influenza virus survived for at least 48 h in one-third of the cases. The unexpected stability of influenza virus in this nonbiological environment suggests that unusual environmental contamination should be considered in the setting of pandemic preparedness.

  13. Survival of Influenza Virus on Banknotes▿

    Science.gov (United States)

    Thomas, Yves; Vogel, Guido; Wunderli, Werner; Suter, Patricia; Witschi, Mark; Koch, Daniel; Tapparel, Caroline; Kaiser, Laurent

    2008-01-01

    Successful control of a viral disease requires knowledge of the different vectors that could promote its transmission among hosts. We assessed the survival of human influenza viruses on banknotes given that billions of these notes are exchanged daily worldwide. Banknotes were experimentally contaminated with representative influenza virus subtypes at various concentrations, and survival was tested after different time periods. Influenza A viruses tested by cell culture survived up to 3 days when they were inoculated at high concentrations. The same inoculum in the presence of respiratory mucus showed a striking increase in survival time (up to 17 days). Similarly, B/Hong Kong/335/2001 virus was still infectious after 1 day when it was mixed with respiratory mucus. When nasopharyngeal secretions of naturally infected children were used, influenza virus survived for at least 48 h in one-third of the cases. The unexpected stability of influenza virus in this nonbiological environment suggests that unusual environmental contamination should be considered in the setting of pandemic preparedness. PMID:18359825

  14. Codon usage bias and the evolution of influenza A viruses. Codon Usage Biases of Influenza Virus

    Directory of Open Access Journals (Sweden)

    Wong Emily HM

    2010-08-01

    Full Text Available Abstract Background The influenza A virus is an important infectious cause of morbidity and mortality in humans and was responsible for 3 pandemics in the 20th century. As the replication of the influenza virus is based on its host's machinery, codon usage of its viral genes might be subject to host selection pressures, especially after interspecies transmission. A better understanding of viral evolution and host adaptive responses might help control this disease. Results Relative Synonymous Codon Usage (RSCU values of the genes from segment 1 to segment 6 of avian and human influenza viruses, including pandemic H1N1, were studied via Correspondence Analysis (CA. The codon usage patterns of seasonal human influenza viruses were distinct among their subtypes and different from those of avian viruses. Newly isolated viruses could be added to the CA results, creating a tool to investigate the host origin and evolution of viral genes. It was found that the 1918 pandemic H1N1 virus contained genes with mammalian-like viral codon usage patterns, indicating that the introduction of this virus to humans was not through in toto transfer of an avian influenza virus. Many human viral genes had directional changes in codon usage over time of viral isolation, indicating the effect of host selection pressures. These changes reduced the overall GC content and the usage of G at the third codon position in the viral genome. Limited evidence of translational selection pressure was found in a few viral genes. Conclusions Codon usage patterns from CA allowed identification of host origin and evolutionary trends in influenza viruses, providing an alternative method and a tool to understand the evolution of influenza viruses. Human influenza viruses are subject to selection pressure on codon usage which might assist in understanding the characteristics of newly emerging viruses.

  15. Efficacy of Influenza Vaccination and Tamiflu? Treatment ? Comparative Studies with Eurasian Swine Influenza Viruses in Pigs

    OpenAIRE

    Duerrwald, Ralf; Schlegel, Michael; Bauer, Katja; Vissiennon, Th?ophile; Wutzler, Peter; Schmidtke, Michaela

    2013-01-01

    Recent epidemiological developments demonstrated that gene segments of swine influenza A viruses can account for antigenic changes as well as reduced drug susceptibility of pandemic influenza A viruses. This raises questions about the efficacy of preventive measures against swine influenza A viruses. Here, the protective effect of vaccination was compared with that of prophylactic Tamiflu® treatment against two Eurasian swine influenza A viruses. 11-week-old pigs were infected by aerosol nebu...

  16. Avian influenza in shorebirds: experimental infection of ruddy turnstones (Arenaria interpres) with avian influenza virus

    OpenAIRE

    Hall, Jeffrey S.; Krauss, Scott; Franson, J. Christian; TeSlaa, Joshua L.; Nashold, Sean W.; Stallknecht, David E.; Webby, Richard J.; Webster, Robert G.

    2012-01-01

    Please cite this paper as: Hall et al. (2012) Avian influenza in shorebirds: experimental infection of ruddy turnstones (Arenaria interpres) with avian influenza virus. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750‐2659.2012.00358.x. Background  Low pathogenic avian influenza viruses (LPAIV) have been reported in shorebirds, especially at Delaware Bay, USA, during spring migration. However, data on patterns of virus excretion, minimal infectious doses, and clinical outcome are l...

  17. Long-term effect of oral immunization against influenza with a gamma-inactivated vaccine in mice

    International Nuclear Information System (INIS)

    Noack, K.; Tischner, H.; Pohl, W.D.; Braeuniger, S.; Nordheim, W.

    1986-01-01

    NMRI mice were immunized orally twice within 10 days with an influenza vaccine inactivated by gamma radiation. The immunization with a relatively low dosis led to the occurence of low specific antibody titer in the lung lavage fluid up to 6th month. Despite of the low titer, immunized mice were protected against aerogenic infection for about 6 months. Protection was demonstrated in comparison to non-immunized mice by a limited increase of cells in bronchoalveolar lavage, low virus titer in the lung and survival of most animals after a lethal aerosol challenge with the live virus. (author)

  18. Molecular detection and typing of influenza viruses. Are we ready for an influenza pandemic?

    NARCIS (Netherlands)

    MacKay, W.G.; Loon, A.M. van; Niedrig, M.; Meijer, A.; Lina, B.; Niesters, H.G.M.

    2008-01-01

    BACKGROUND: We cannot predict when an influenza pandemic will occur or which variant of the virus will cause it. Little information is currently available on the ability of laboratories to detect and subtype influenza viruses including the avian influenza viruses. OBJECTIVES: To assess the ability

  19. Original antigenic sin responses to influenza viruses.

    Science.gov (United States)

    Kim, Jin Hyang; Skountzou, Ioanna; Compans, Richard; Jacob, Joshy

    2009-09-01

    Most immune responses follow Burnet's rule in that Ag recruits specific lymphocytes from a large repertoire and induces them to proliferate and differentiate into effector cells. However, the phenomenon of "original antigenic sin" stands out as a paradox to Burnet's rule of B cell engagement. Humans, upon infection with a novel influenza strain, produce Abs against older viral strains at the expense of responses to novel, protective antigenic determinants. This exacerbates the severity of the current infection. This blind spot of the immune system and the redirection of responses to the "original Ag" rather than to novel epitopes were described fifty years ago. Recent reports have questioned the existence of this phenomenon. Hence, we revisited this issue to determine the extent to which original antigenic sin is induced by variant influenza viruses. Using two related strains of influenza A virus, we show that original antigenic sin leads to a significant decrease in development of protective immunity and recall responses to the second virus. In addition, we show that sequential infection of mice with two live influenza virus strains leads to almost exclusive Ab responses to the first viral strain, suggesting that original antigenic sin could be a potential strategy by which variant influenza viruses subvert the immune system.

  20. CAF01 potentiates immune responses and efficacy of an inactivated influenza vaccine in ferrets.

    Directory of Open Access Journals (Sweden)

    Cyril Jean-Marie Martel

    Full Text Available Trivalent inactivated vaccines (TIV against influenza are given to 350 million people every year. Most of these are non-adjuvanted vaccines whose immunogenicity and protective efficacy are considered suboptimal. Commercially available non-adjuvanted TIV are known to elicit mainly a humoral immune response, whereas the induction of cell-mediated immune responses is negligible. Recently, a cationic liposomal adjuvant (dimethyldioctadecylammonium/trehalose 6,6'-dibehenate, CAF01 was developed. CAF01 has proven to enhance both humoral and cell-mediated immune responses to a number of different experimental vaccine candidates. In this study, we compared the immune responses in ferrets to a commercially available TIV with the responses to the same vaccine mixed with the CAF01 adjuvant. Two recently circulating H1N1 viruses were used as challenge to test the vaccine efficacy. CAF01 improved the immunogenicity of the vaccine, with increased influenza-specific IgA and IgG levels. Additionally, CAF01 promoted cellular-mediated immunity as indicated by interferon-gamma expressing lymphocytes, measured by flow cytometry. CAF01 also enhanced the protection conferred by the vaccine by reducing the viral load measured in nasal washes by RT-PCR. Finally, CAF01 allowed for dose-reduction and led to higher levels of protection compared to TIV adjuvanted with a squalene emulsion. The data obtained in this human-relevant challenge model supports the potential of CAF01 in future influenza vaccines.

  1. New Kids on the Block: RNA-Based Influenza Virus Vaccines.

    Science.gov (United States)

    Scorza, Francesco Berlanda; Pardi, Norbert

    2018-04-01

    RNA-based immunization strategies have emerged as promising alternatives to conventional vaccine approaches. A substantial body of published work demonstrates that RNA vaccines can elicit potent, protective immune responses against various pathogens. Consonant with its huge impact on public health, influenza virus is one of the best studied targets of RNA vaccine research. Currently licensed influenza vaccines show variable levels of protection against seasonal influenza virus strains but are inadequate against drifted and pandemic viruses. In recent years, several types of RNA vaccines demonstrated efficacy against influenza virus infections in preclinical models. Additionally, comparative studies demonstrated the superiority of some RNA vaccines over the currently used inactivated influenza virus vaccines in animal models. Based on these promising preclinical results, clinical trials have been initiated and should provide valuable information about the translatability of the impressive preclinical data to humans. This review briefly describes RNA-based vaccination strategies, summarizes published preclinical and clinical data, highlights the roadblocks that need to be overcome for clinical applications, discusses the landscape of industrial development, and shares the authors' personal perspectives about the future of RNA-based influenza virus vaccines.

  2. Seasonal and pandemic human influenza viruses attach better to human upper respiratory tract epithelium than avian influenza viruses.

    Science.gov (United States)

    van Riel, Debby; den Bakker, Michael A; Leijten, Lonneke M E; Chutinimitkul, Salin; Munster, Vincent J; de Wit, Emmie; Rimmelzwaan, Guus F; Fouchier, Ron A M; Osterhaus, Albert D M E; Kuiken, Thijs

    2010-04-01

    Influenza viruses vary markedly in their efficiency of human-to-human transmission. This variation has been speculated to be determined in part by the tropism of influenza virus for the human upper respiratory tract. To study this tropism, we determined the pattern of virus attachment by virus histochemistry of three human and three avian influenza viruses in human nasal septum, conchae, nasopharynx, paranasal sinuses, and larynx. We found that the human influenza viruses-two seasonal influenza viruses and pandemic H1N1 virus-attached abundantly to ciliated epithelial cells and goblet cells throughout the upper respiratory tract. In contrast, the avian influenza viruses, including the highly pathogenic H5N1 virus, attached only rarely to epithelial cells or goblet cells. Both human and avian viruses attached occasionally to cells of the submucosal glands. The pattern of virus attachment was similar among the different sites of the human upper respiratory tract for each virus tested. We conclude that influenza viruses that are transmitted efficiently among humans attach abundantly to human upper respiratory tract, whereas inefficiently transmitted influenza viruses attach rarely. These results suggest that the ability of an influenza virus to attach to human upper respiratory tract is a critical factor for efficient transmission in the human population.

  3. The Influence of Ecological Factors on the Transmission and Stability of Avian Influenza Virus in the Environment

    Directory of Open Access Journals (Sweden)

    Dyah Ayu Hewajuli

    2014-09-01

    Full Text Available Ecology is a science studying the correlation among organisms and some environmental factors. Ecological factors play an important role to transmit Avian Influenza (AI virus and influence its stability in the environment. Avian Influenza virus is classified as type A virus and belong to Orthomyxoviridae family. The virus can infect various vertebrates, mainly birds and mammals, including human. Avian Influenza virus transmission can occur through bird migration. The bird migration patterns usually occur in the large continent covers a long distance area within a certain periode hence transmit the virus from infected birds to other birds and spread to the environment. The biotic (normal flora microbes and abiotic (physical and chemical factors play important role in transmitting the virus to susceptible avian species and influence its stability in the environment. Disinfectant can inactivate the AI virus in the environment but its effectivity is influenced by the concentration, contact time, pH, temperature and organic matter.

  4. Cost Effectiveness of Influenza Vaccine for U.S. Children: Live Attenuated and Inactivated Influenza Vaccine.

    Science.gov (United States)

    Shim, Eunha; Brown, Shawn T; DePasse, Jay; Nowalk, Mary Patricia; Raviotta, Jonathan M; Smith, Kenneth J; Zimmerman, Richard K

    2016-09-01

    Prior studies showed that live attenuated influenza vaccine (LAIV) is more effective than inactivated influenza vaccine (IIV) in children aged 2-8 years, supporting the Centers for Disease Control and Prevention (CDC) recommendations in 2014 for preferential LAIV use in this age group. However, 2014-2015 U.S. effectiveness data indicated relatively poor effectiveness of both vaccines, leading CDC in 2015 to no longer prefer LAIV. An age-structured model of influenza transmission and vaccination was developed, which incorporated both direct and indirect protection induced by vaccination. Based on this model, the cost effectiveness of influenza vaccination strategies in children aged 2-8 years in the U.S. was estimated. The base case assumed a mixed vaccination strategy where 33.3% and 66.7% of vaccinated children aged 2-8 years receive LAIV and IIV, respectively. Analyses were performed in 2014-2015. Using published meta-analysis vaccine effectiveness data (83% LAIV and 64% IIV), exclusive LAIV use would be a cost-effective strategy when vaccinating children aged 2-8 years, whereas IIV would not be preferred. However, when 2014-2015 U.S. effectiveness data (0% LAIV and 15% IIV) were used, IIV was likely to be preferred. The cost effectiveness of influenza vaccination in children aged 2-8 years is highly dependent on vaccine effectiveness; the vaccine type with higher effectiveness is preferred. In general, exclusive IIV use is preferred over LAIV use, as long as vaccine effectiveness is higher for IIV than for LAIV. Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  5. Immune response in domestic ducks following intradermal delivery of inactivated vaccine against H5N1 highly pathogenic avian influenza virus adjuvanted with oligodeoxynucleotides containing CpG motifs.

    Science.gov (United States)

    Yuk, Seong-Su; Lee, Dong-Hun; Park, Jae-Keun; To, Eredene-Ochir; Kwon, Jung-Hoon; Noh, Jin-Yong; Gomis, Susantha; Song, Chang-Seon

    2015-08-01

    Ducks are a natural reservoir for H5N1 highly pathogenic avian influenza (HPAI) viruses, which produces a range of clinical outcomes from asymptomatic infections to severe disease with mortality. Vaccination against HPAI is one of the few methods available for controlling avian influenza virus (AIV) infection in domestic ducks; therefore, it is necessary to improve vaccine efficacy against HPAI in domestic ducks. However, few studies have focused on enhancing the immune response by testing alternative administration routes and adjuvants. While attempting to maximize the efficacy of a vaccine, it is important to select an appropriate vaccine delivery route and adjuvant to elicit an enhanced immune response. Although several studies have indicated that the vaccination of ducks against HPAI viruses has offered protection against lethal virus challenge, the immunogenicity of the vaccine still requires improvement. In this study, we characterized the immune response following a novel vaccination strategy against H5N1 HPAI virus in domestic ducks. Our novel intradermal delivery system and the application of the cytosine-phosphodiester-guanine (CpG) oligodeoxynucleotide (ODN) adjuvant allowed us to obtain information regarding the sustained vaccine immunity. Compared with the intramuscular route of vaccination, the intradermal route resulted in higher antibody titer as well as lower antibody deviation following secondary vaccination. In addition, the use of a CpG-ODN adjuvant had a dose-sparing effect on antibody titer. Furthermore, when a high dose of antigen was used, the CpG-ODN-adjuvanted vaccine maintained a high mean antibody titer. This data demonstrates that intradermal immunization combined with administration of CpG-ODN as an adjuvant may be a promising strategy for improving vaccine efficacy in domestic ducks. © 2015 Poultry Science Association Inc.

  6. The control of H5 or H7 mildly pathogenic avian influenza: a role for inactivated vaccine.

    Science.gov (United States)

    Halvorson, David A

    2002-02-01

    Biosecurity is the first line of defence in the prevention and control of mildly pathogenic avian influenza (MPAI). Its use has been highly successful in keeping avian influenza (AI) out of commercial poultry worldwide. However, sometimes AI becomes introduced into poultry populations and, when that occurs, biosecurity again is the primary means of controlling the disease. There is agreement that routine serological monitoring, disease reporting, isolation or quarantine of affected flocks, application of strict measures to prevent the contamination of and movement of people and equipment, and changing flock schedules are necessities for controlling AI. There is disagreement as to the disposition of MPAI-infected flocks: some advocate their destruction and others advocate controlled marketing. Sometimes biosecurity is not enough to stop the spread of MPAI. In general, influenza virus requires a dense population of susceptible hosts to maintain itself. When there is a large population of susceptible poultry in an area, use of an inactivated AI vaccine can contribute to AI control by reducing the susceptibility of the population. Does use of inactivated vaccine assist, complicate or interfere with AI control and eradication? Yes, it assists MPAI control (which may reduce the risk of highly pathogenic AI (HPAI)) but, unless steps are taken to prevent it, vaccination may interfere with sero-epidemiology in the case of an HPAI outbreak. Does lack of vaccine assist, complicate or interfere with AI control and eradication? Yes, it assists in identification of sero-positive (convalescent) flocks in a HPAI eradication program, but it interferes with MPAI control (which in turn may increase the risk of emergence of HPAI).A number of hypothetical concerns have been raised about the use of inactivated AI vaccines. Infection of vaccinated flocks, serology complications and spreading of virus by vaccine crews are some of the hypothetical concerns. The discussion of these concerns

  7. Safety, efficacy, and immunogenicity of an inactivated influenza vaccine in healthy adults: a randomized, placebo-controlled trial over two influenza seasons

    Directory of Open Access Journals (Sweden)

    Bouveret Nancy

    2010-03-01

    Full Text Available Abstract Background Seasonal influenza imposes a substantial personal morbidity and societal cost burden. Vaccination is the major strategy for influenza prevention; however, because antigenically drifted influenza A and B viruses circulate annually, influenza vaccines must be updated to provide protection against the predicted prevalent strains for the next influenza season. The aim of this study was to assess the efficacy, safety, reactogenicity, and immunogenicity of a trivalent inactivated split virion influenza vaccine (TIV in healthy adults over two influenza seasons in the US. Methods The primary endpoint of this double-blind, randomized study was the average efficacy of TIV versus placebo for the prevention of vaccine-matched, culture-confirmed influenza (VMCCI across the 2005-2006 and 2006-2007 influenza seasons. Secondary endpoints included the prevention of laboratory-confirmed (defined by culture and/or serology influenza, as well as safety, reactogenicity, immunogenicity, and consistency between three consecutive vaccine lots. Participants were assessed actively during both influenza seasons, and nasopharyngeal swabs were collected for viral culture from individuals with influenza-like illness. Blood specimens were obtained for serology one month after vaccination and at the end of each influenza season's surveillance period. Results Although the point estimate for efficacy in the prevention of all laboratory-confirmed influenza was 63.2% (97.5% confidence interval [CI] lower bound of 48.2%, the point estimate for the primary endpoint, efficacy of TIV against VMCCI across both influenza seasons, was 46.3% with a 97.5% CI lower bound of 9.8%. This did not satisfy the pre-specified success criterion of a one-sided 97.5% CI lower bound of >35% for vaccine efficacy. The VMCCI attack rates were very low overall at 0.6% and 1.2% in the TIV and placebo groups, respectively. Apart from a mismatch for influenza B virus lineage in 2005

  8. Comparison of the Effectiveness of Trivalent Inactivated Influenza Vaccine and Live, Attenuated Influenza Vaccine in Preventing Influenza-Like Illness among US Service Members, 2006-2009

    Science.gov (United States)

    2012-11-26

    controlled studies. Vaccine 2012; 30:886–92. 11. Piedra PA, Gaglani MJ, Kozinetz CA, et al. Trivalent live attenuated intranasal influenza vaccine...120:e553–64. 12. Halloran ME, Piedra PA, Longini IM Jr, et al. Efficacy of trivalent, cold-adapted, influenza virus vaccine against influenza A (Fujian

  9. Dual Infection of Novel Influenza Viruses A/H1N1 and A/H3N2 in a Cluster of Cambodian Patients

    Science.gov (United States)

    2011-01-01

    influenza viruses as well as the avian influenza virus A/H5N1...on full genome sequencing. This incident confirms dual influenza virus infections and highlights the risk of zoonotic and seasonal influenza viruses ...North American swine influenza viruses , North American avian influenza viruses , human influenza viruses , and a Eurasian swine influenza virus . 18

  10. Inactivation of Lassa, Marburg, and Ebola viruses by gamma irradiation

    International Nuclear Information System (INIS)

    Elliott, L.H.; McCormick, J.B.; Johnson, K.M.

    1982-01-01

    Because of the cumbersome conditions experienced in a maximum containment laboratory, methods for inactivating highly pathogenic viruses were investigated. The infectivity of Lassa, Marburg, and Ebola viruses was inactivated without altering the immunological activity after radiation with 60 CO gamma rays. At 4 degrees C, Lassa virus was the most difficult to inactivate with a rate of 5.3 X 10(-6) log 50% tissue culture infective dose per rad of 60 CO radiation, as compared with 6.8 X 10(-6) log 50% tissue culture infective dose per rad for Ebola virus and 8.4 X 10(-6) log 50% tissue culture infective dose per rad for Marburg virus. Experimental inactivation curves, as well as curves giving the total radiation needed to inactivate a given concentration of any of the three viruses, are presented. The authors found this method of inactivation to be superior to UV light or beta-propiolactone inactivation and now routinely use it for preparation of material for protein-chemistry studies or for preparation of immunological reagents

  11. Inactivation of Lassa, Marburg, and Ebola viruses by gamma irradiation

    International Nuclear Information System (INIS)

    Elliott, L.H.; McCormick, J.B.; Johnson, K.M.

    1982-01-01

    Because of the cumbersome conditions experienced in a maximum containment laboratory, methods for inactivating highly pathogenic viruses were investigated. The infectivity of Lassa, Marburg, and Ebola viruses was inactivated without altering the immunological activity after radiation with 60 Co gamma rays. At 4 degrees C, Lassa virus was the most difficult to inactivate with a rate of 5.3 X 10(-6) log 50% tissue culture infective dose per rad of 60 Co radiation, as compared with 6.8 X 10(-6) log 50% tissue culture infective dose per rad for Ebola virus and 8.4 X 10(-6) log 50% tissue culture infective dose per rad for Marburg virus. Experimental inactivation curves, as well as curves giving the total radiation needed to inactivate a given concentration of any of the three viruses, are presented. We found this method of inactivation to be superior to UV light or beta-propiolactone inactivation and now routinely use it for preparation of material for protein-chemistry studies or for preparation of immunological reagents

  12. Influenza virus infection among pediatric patients reporting diarrhea and influenza-like illness

    Directory of Open Access Journals (Sweden)

    Uyeki Timothy M

    2010-01-01

    Full Text Available Abstract Background Influenza is a major cause of morbidity and hospitalization among children. While less often reported in adults, gastrointestinal symptoms have been associated with influenza in children, including abdominal pain, nausea, vomiting, and diarrhea. Methods From September 2005 and April 2008, pediatric patients in Indonesia presenting with concurrent diarrhea and influenza-like illness were enrolled in a study to determine the frequency of influenza virus infection in young patients presenting with symptoms less commonly associated with an upper respiratory tract infection (URTI. Stool specimens and upper respiratory swabs were assayed for the presence of influenza virus. Results Seasonal influenza A or influenza B viral RNA was detected in 85 (11.6% upper respiratory specimens and 21 (2.9% of stool specimens. Viable influenza B virus was isolated from the stool specimen of one case. During the time of this study, human infections with highly pathogenic avian influenza A (H5N1 virus were common in the survey area. However, among 733 enrolled subjects, none had evidence of H5N1 virus infection. Conclusions The detection of influenza viral RNA and viable influenza virus from stool suggests that influenza virus may be localized in the gastrointestinal tract of children, may be associated with pediatric diarrhea and may serve as a potential mode of transmission during seasonal and epidemic influenza outbreaks.

  13. Radioimmunoassay of influenza A virus haemagglutinin. I

    International Nuclear Information System (INIS)

    Russ, G.; Styk, B.; Polakova, K.

    1978-01-01

    Haemagglutinin released from influenza A virus recombinant MRC11 [antigenically identical to the strain A/Port Chalmers/1/73 (H3N2)] by bromelain treatment and purified by rate zonal centrifugation (further on B-HA) was examined for possible contamination by neuraminidase. Specific enzymatic activities of the MRC11 virus and the B-HA respectively showed that B-HA contained less than 0.1% of enzymatically active neuraminidase originally present in the virus. Gel double diffusion tests, specificities of rabbit antisera induced by B-HA as well as radioimmunoprecipitation experiments demonstrated that B-HA was devoid of any antigenically active neuraminidase. Precipitation of 125 I-labelled B-HA with antisera to influenza virus recombinants with N2 neuraminidase was evidently caused by antibodies to host antigenic determinant(s) present in these sera. As for purity and radioimmunoprecipitation properties, B-HA is quite suitable for radioimmunoassay experiments. (author)

  14. Circulating avian influenza viruses closely related to the 1918 virus have pandemic potential

    Science.gov (United States)

    Watanabe, Tokiko; Zhong, Gongxun; Russell, Colin A.; Nakajima, Noriko; Hatta, Masato; Hanson, Anthony; McBride, Ryan; Burke, David F.; Takahashi, Kenta; Fukuyama, Satoshi; Tomita, Yuriko; Maher, Eileen A.; Watanabe, Shinji; Imai, Masaki; Neumann, Gabriele; Hasegawa, Hideki; Paulson, James C.; Smith, Derek J.; Kawaoka, Yoshihiro

    2014-01-01

    Summary Wild birds harbor a large gene pool of influenza A viruses that have the potential to cause influenza pandemics. Foreseeing and understanding this potential is important for effective surveillance. Our phylogenetic and geographic analyses revealed the global prevalence of avian influenza virus genes whose proteins differ only a few amino acids from the 1918 pandemic influenza virus, suggesting that 1918-like pandemic viruses may emerge in the future. To assess this risk, we generated and characterized a virus composed of avian influenza viral segments with high homology to the 1918 virus. This virus exhibited higher pathogenicity in mice and ferrets than an authentic avian influenza virus. Further, acquisition of seven amino acid substitutions in the viral polymerases and the hemagglutinin surface glycoprotein conferred respiratory droplet transmission to the 1918-like avian virus in ferrets, demonstrating that contemporary avian influenza viruses with 1918 virus-like proteins may have pandemic potential. PMID:24922572

  15. Conducting polymers as sorbents of influenza viruses

    Czech Academy of Sciences Publication Activity Database

    Ivanova, V. T.; Garina, E. O.; Burtseva, E. I.; Kirillova, E. S.; Ivanova, M. V.; Stejskal, Jaroslav; Sapurina, Irina

    2017-01-01

    Roč. 71, č. 2 (2017), s. 495-503 ISSN 0366-6352 R&D Projects: GA ČR(CZ) GA16-02787S; GA MŠk(CZ) LH14199 Institutional support: RVO:61389013 Keywords : influenza viruses * conducting polymers * polyaniline Subject RIV: CD - Macromolecular Chemistry OBOR OECD: Polymer science Impact factor: 1.258, year: 2016

  16. Virus genetic variations and evade from immune system, the present influenza challenges: review article

    Directory of Open Access Journals (Sweden)

    Shahla Shahsavandi

    2015-10-01

    Full Text Available The spread of influenza viruses in multiple bird and mammalian species is a worldwide serious threat to human and animal populations' health and raise major concern for ongoing pandemic in humans. Direct transmission of the avian viruses which have sialic acid specific receptors similar to human influenza viruses are a warning to the emergence of a new mutant strain that is likely to share molecular determinants to facilitate their replication in human host. So the emerge virus can be transmitted easily through person to person. The genetic variations of the influenza viruses, emerge and re-emerge of new antigenic variants, and transmission of avian influenza viruses to human may raise wide threat to public health and control of pandemic influenza. Vaccination, chemoprophylaxis with specific antiviral drugs, and personal protective non-pharmacological measures are tools to treat influenza virus infection. The emergence of drug resistant strains of influenza viruses under drug selective pressure and their limited efficacy in severe cases of influenza infections highlight the need to development of new therapies with alternative modes. In recent years several studies have been progressed to introduce components to be act at different stages of the viral life cycle with broad spectrum reactivity against mammalian and bird influenza subtypes. A wide variety of different antiviral strategies include inhibition of virus entry, blocking of viral replication or targeting of cellular signaling pathways have been explored. The current inactivated influenza vaccines are eliciting only B-cell responses. Application of the vaccines has been limited due to the emergence of the new virus antigenic variants. In recent decade development of gene vaccines by targeting various influenza virus proteins have been interested because significant potential for induction of both humoral and cell mediated immunity responses. Enhanced and directed immune responses to

  17. A cell culture-derived whole virus influenza A vaccine based on magnetic sulfated cellulose particles confers protection in mice against lethal influenza A virus infection.

    Science.gov (United States)

    Pieler, Michael M; Frentzel, Sarah; Bruder, Dunja; Wolff, Michael W; Reichl, Udo

    2016-12-07

    Downstream processing and formulation of viral vaccines employs a large number of different unit operations to achieve the desired product qualities. The complexity of individual process steps involved, the need for time consuming studies towards the optimization of virus yields, and very high requirements regarding potency and safety of vaccines results typically in long lead times for the establishment of new processes. To overcome such obstacles, to enable fast screening of potential vaccine candidates, and to explore options for production of low cost veterinary vaccines a new platform for whole virus particle purification and formulation based on magnetic particles has been established. Proof of concept was carried out with influenza A virus particles produced in suspension Madin Darby canine kidney (MDCK) cells. The clarified, inactivated, concentrated, and diafiltered virus particles were bound to magnetic sulfated cellulose particles (MSCP), and directly injected into mice for immunization including positive and negative controls. We show here, that in contrast to the mock-immunized group, vaccination of mice with antigen-loaded MSCP (aMSCP) resulted in high anti-influenza A antibody responses and full protection against a lethal challenge with replication competent influenza A virus. Antiviral protection correlated with a 400-fold reduced number of influenza nucleoprotein gene copies in the lungs of aMSCP immunized mice compared to mock-treated animals, indicating the efficient induction of antiviral immunity by this novel approach. Thus, our data proved the use of MSCP for purification and formulation of the influenza vaccine to be fast and efficient, and to confer protection of mice against influenza A virus infection. Furthermore, the method proposed has the potential for fast purification of virus particles directly from bioreactor harvests with a minimum number of process steps towards formulation of low-cost veterinary vaccines, and for screening

  18. An infectious bat-derived chimeric influenza virus harbouring the entry machinery of an influenza A virus.

    Science.gov (United States)

    Juozapaitis, Mindaugas; Aguiar Moreira, Étori; Mena, Ignacio; Giese, Sebastian; Riegger, David; Pohlmann, Anne; Höper, Dirk; Zimmer, Gert; Beer, Martin; García-Sastre, Adolfo; Schwemmle, Martin

    2014-07-23

    In 2012, the complete genomic sequence of a new and potentially harmful influenza A-like virus from bats (H17N10) was identified. However, infectious influenza virus was neither isolated from infected bats nor reconstituted, impeding further characterization of this virus. Here we show the generation of an infectious chimeric virus containing six out of the eight bat virus genes, with the remaining two genes encoding the haemagglutinin and neuraminidase proteins of a prototypic influenza A virus. This engineered virus replicates well in a broad range of mammalian cell cultures, human primary airway epithelial cells and mice, but poorly in avian cells and chicken embryos without further adaptation. Importantly, the bat chimeric virus is unable to reassort with other influenza A viruses. Although our data do not exclude the possibility of zoonotic transmission of bat influenza viruses into the human population, they indicate that multiple barriers exist that makes this an unlikely event.

  19. tion and/or treatment of influenza virus infections

    African Journals Online (AJOL)

    Repro

    more frequent in children and more seri- ous in the elderly, ... The main option for the prevention of influenza and ... rapid development of influenza virus resistance ... drugs that affect the CNS, particu- .... include employees of hospitals, clinics ...

  20. Global Surveillance of Emerging Influenza Virus Genotypes by Mass Spectrometry

    Science.gov (United States)

    2007-05-30

    Intercontinental circulation of human influenza A( H1N2 ) reassortant viruses during the 2001–2002 influenza season. J Infect Dis 186: 1490–1493. 6. Taubenberger...Global Surveillance of Emerging Influenza Virus Genotypes by Mass Spectrometry Rangarajan Sampath1*, Kevin L. Russell2, Christian Massire1, Mark W...Infections and Immunity, University of Texas Medical Branch, Galveston, Texas, United States of America Background. Effective influenza surveillance requires

  1. Simplifying influenza vaccination during pandemics : sublingual priming and intramuscular boosting of immune responses with heterologous whole inactivated influenza vaccine

    NARCIS (Netherlands)

    Murugappan, Senthil; Patil, Harshad P; Frijlink, Henderik W; Huckriede, Anke; Hinrichs, Wouter L J

    2014-01-01

    The best approach to control the spread of influenza virus during a pandemic is vaccination. Yet, an appropriate vaccine is not available early in the pandemic since vaccine production is time consuming. For influenza strains with a high pandemic potential like H5N1, stockpiling of vaccines has been

  2. Localization of influenza virus proteins to nuclear dot 10 structures in influenza virus-infected cells

    International Nuclear Information System (INIS)

    Sato, Yoshiko; Yoshioka, Kenichi; Suzuki, Chie; Awashima, Satoshi; Hosaka, Yasuhiro; Yewdell, Jonathan; Kuroda, Kazumichi

    2003-01-01

    We studied influenza virus M1 protein by generating HeLa and MDCK cell lines that express M1 genetically fused to green fluorescent protein (GFP). GFP-M1 was incorporated into virions produced by influenza virus infected MDCK cells expressing the fusion protein indicating that the fusion protein is at least partially functional. Following infection of either HeLa or MDCK cells with influenza A virus (but not influenza B virus), GFP-M1 redistributes from its cytosolic/nuclear location and accumulates in nuclear dots. Immunofluorescence revealed that the nuclear dots represent nuclear dot 10 (ND10) structures. The colocalization of authentic M1, as well as NS1 and NS2 protein, with ND10 was confirmed by immunofluorescence following in situ isolation of ND10. These findings demonstrate a previously unappreciated involvement of influenza virus with ND10, a structure involved in cellular responses to immune cytokines as well as the replication of a rapidly increasing list of viruses

  3. Avian Influenza A (H7N9) Virus

    Science.gov (United States)

    ... August 7, 2017 Increase in Human Infections with Avian Influenza A(H7N9) Virus During the Fifth Epidemic — China, October 2016–February 2017 Antigenic and genetic characteristics of zoonotic influenza viruses and candidate vaccine viruses developed for ...

  4. Transmission of Influenza B Viruses in the Guinea Pig

    Science.gov (United States)

    Pica, Natalie; Chou, Yi-Ying; Bouvier, Nicole M.

    2012-01-01

    Epidemic influenza is typically caused by infection with viruses of the A and B types and can result in substantial morbidity and mortality during a given season. Here we demonstrate that influenza B viruses can replicate in the upper respiratory tract of the guinea pig and that viruses of the two main lineages can be transmitted with 100% efficiency between inoculated and naïve animals in both contact and noncontact models. Our results also indicate that, like in the case for influenza A virus, transmission of influenza B viruses is enhanced at colder temperatures, providing an explanation for the seasonality of influenza epidemics in temperate climates. We therefore present, for the first time, a small animal model with which to study the underlying mechanisms of influenza B virus transmission. PMID:22301149

  5. Characterisation and Identification of Avian Influenza Virus (AI

    Directory of Open Access Journals (Sweden)

    Dyah Ayu Hewajuli

    2008-06-01

    Full Text Available Avian Influenza is caused by Influenza A virus which is a member of Orthomyxoviridae family. Influenza A virus is enveloped single stranded RNA with eight-segmented, negative polarity and filament or oval form, 50 – 120 by 200 – 300 nm diameters. Influenza A viruses have been found to infect birds, human, pig, horse and sometimes in the other mammalian such as seal and whale. The viruses are divided into different subtypes based on the antigenic protein which covers the virus surface i.e. Haemaglutinin (HA and Neuraminidase (NA. In addition, the nomenclature of subtype virus is based on HA and NA i.e HxNx, for example H5N1, H9N2 and the others. According to pathogenic, it could be divided into two distinct groups, they are Highly Pathogenic Avian Influenza (HPAI and Low Pathogenic Avian Influenza (LPAI. The Avian Influenza viruses have been continuously occurred and spread out in some continents such us America, Europe, Africa and Asian countries. The outbreak of Avian Influenza caused high mortality on birds and it has been reported that in human case Avian Influenza subtype H5N1 virus has caused several deaths. To anticipate this condition, an effort to prevent the transmission of Avian Influenza is needed. These strategic attempts include biosecurity, depopulation, vaccination, control of virus movement, monitoring and evaluation. Laboratory diagnostic plays an important role for successful prevention, control and eradication programs of Avian Influenza. Recently, there are two diagnostic methods for Avian Influenza. They are conventional (virological diagnosis and molecular methods. The conventional method is usually used for initial diagnostic of Avian Influenza. The conventional method takes more time and more costly, whereas the molecular method is more effective than conventional method. Based on the available diagnostic technique, basically diagnostic of Avian Influenza is done by serology test, isolation and identification as well

  6. Sialic acid tissue distribution and influenza virus tropism

    OpenAIRE

    Kumlin, Urban; Olofsson, Sigvard; Dimock, Ken; Arnberg, Niklas

    2008-01-01

    Abstract? Avian influenza A viruses exhibit a strong preference for using ?2,3?linked sialic acid as a receptor. Until recently, the presumed lack of this receptor in human airways was believed to constitute an efficient barrier to avian influenza A virus infection of humans. Recent zoonotic outbreaks of avian influenza A virus have triggered researchers to analyse tissue distribution of sialic acid in further detail. Here, we review and extend the current knowledge about sialic acid distribu...

  7. Influenza Virus and Glycemic Variability in Diabetes: A Killer Combination?

    Directory of Open Access Journals (Sweden)

    Katina D. Hulme

    2017-05-01

    Full Text Available Following the 2009 H1N1 influenza virus pandemic, numerous studies identified the striking link between diabetes mellitus and influenza disease severity. Typically, influenza virus is a self-limiting infection but in individuals who have a pre-existing chronic illness, such as diabetes mellitus, severe influenza can develop. Here, we discuss the latest clinical and experimental evidence for the role of diabetes in predisposing the host to severe influenza. We explore the possible mechanisms that underlie this synergy and highlight the, as yet, unexplored role that blood glucose oscillations may play in disease development. Diabetes is one of the world’s fastest growing chronic diseases and influenza virus represents a constant and pervasive threat to human health. It is therefore imperative that we understand how diabetes increases influenza severity in order to mitigate the burden of future influenza epidemics and pandemics.

  8. Cross talk between animal and human influenza viruses.

    Science.gov (United States)

    Ozawa, Makoto; Kawaoka, Yoshihiro

    2013-01-01

    Although outbreaks of highly pathogenic avian influenza in wild and domestic birds have been posing the threat of a new influenza pandemic for the past decade, the first pandemic of the twenty-first century came from swine viruses. This fact emphasizes the complexity of influenza viral ecology and the difficulty of predicting influenza viral dynamics. Complete control of influenza viruses seems impossible. However, we must minimize the impact of animal and human influenza outbreaks by learning lessons from past experiences and recognizing the current status. Here, we review the most recent influenza virology data in the veterinary field, including aspects of zoonotic agents and recent studies that assess the pandemic potential of H5N1 highly pathogenic avian influenza viruses.

  9. DAMPs and influenza virus infection in ageing.

    Science.gov (United States)

    Samy, Ramar Perumal; Lim, Lina H K

    2015-11-01

    Influenza A virus (IAV) is a serious global health problem worldwide due to frequent and severe outbreaks. IAV causes significant morbidity and mortality in the elderly population, due to the ineffectiveness of the vaccine and the alteration of T cell immunity with ageing. The cellular and molecular link between ageing and virus infection is unclear and it is possible that damage associated molecular patterns (DAMPs) may play a role in the raised severity and susceptibility of virus infections in the elderly. DAMPs which are released from damaged cells following activation, injury or cell death can activate the immune response through the stimulation of the inflammasome through several types of receptors found on the plasma membrane, inside endosomes after endocytosis as well as in the cytosol. In this review, the detriment in the immune system during ageing and the links between influenza virus infection and ageing will be discussed. In addition, the role of DAMPs such as HMGB1 and S100/Annexin in ageing, and the enhanced morbidity and mortality to severe influenza infection in ageing will be highlighted. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. AS03-adjuvanted versus non-adjuvanted inactivated trivalent influenza vaccine against seasonal influenza in elderly people: a phase 3 randomised trial

    NARCIS (Netherlands)

    McElhaney, J.E.; Beran, J.; Devaster, J.M.; Esen, M.; Launay, O.; Leroux-Roels, G.; Ruiz-Palacios, G.M.; Essen, G.A. van; Caplanusi, A.; Claeys, C.; Durand, C.; Duval, X.; Idrissi, M. El; Falsey, A.R.; Feldman, G.; Frey, S.E.; Galtier, F.; Hwang, S.J.; Innis, B.L.; Kovac, M.; Kremsner, P.; McNeil, S.; Nowakowski, A.; Richardus, J.H.; Trofa, A.; Oostvogels, L.; Verheugt, F.W.; et al.,

    2013-01-01

    BACKGROUND: We aimed to compare AS03-adjuvanted inactivated trivalent influenza vaccine (TIV) with non-adjuvanted TIV for seasonal influenza prevention in elderly people. METHODS: We did a randomised trial in 15 countries worldwide during the 2008-09 (year 1) and 2009-10 (year 2) influenza seasons.

  11. Inactivation of viruses in bubbling processes utilized for personal bioaerosol monitoring.

    Science.gov (United States)

    Agranovski, I E; Safatov, A S; Borodulin, A I; Pyankov, O V; Petrishchenko, V A; Sergeev, A N; Agafonov, A P; Ignatiev, G M; Sergeev, A A; Agranovski, V

    2004-12-01

    A new personal bioaerosol sampler has recently been developed and evaluated for sampling of viable airborne bacteria and fungi under controlled laboratory conditions and in the field. The operational principle of the device is based on the passage of air through porous medium immersed in liquid. This process leads to the formation of bubbles within the filter as the carrier gas passes through and thus provides effective mechanisms for aerosol removal. As demonstrated in previous studies, the culturability of sampled bacterium and fungi remained high for the entire 8-h sampling period. The present study is the first step of the evaluation of the new sampler for monitoring of viable airborne viruses. It focuses on the investigation of the inactivation rate of viruses in the bubbling process during 4 h of continuous operation. Four microbes were used in this study, influenza, measles, mumps, and vaccinia viruses. It was found that the use of distilled water as the collection fluid was associated with a relatively high decay rate. A significant improvement was achieved by utilizing virus maintenance fluid prepared by using Hank's solution with appropriate additives. The survival rates of the influenza, measles, and mumps viruses were increased by 1.4 log, 0.83 log, and 0.82 log, respectively, after the first hour of operation compared to bubbling through the sterile water. The same trend was observed throughout the entire 4-h experiment. There was no significant difference observed only for the robust vaccinia virus.

  12. Mucosal Immunity and Protective Efficacy of Intranasal Inactivated Influenza Vaccine Is Improved by Chitosan Nanoparticle Delivery in Pigs

    Directory of Open Access Journals (Sweden)

    Santosh Dhakal

    2018-05-01

    Full Text Available Annually, swine influenza A virus (SwIAV causes severe economic loss to swine industry. Currently used inactivated SwIAV vaccines administered by intramuscular injection provide homologous protection, but limited heterologous protection against constantly evolving field viruses, attributable to the induction of inadequate levels of mucosal IgA and cellular immune responses in the respiratory tract. A novel vaccine delivery platform using mucoadhesive chitosan nanoparticles (CNPs administered through intranasal (IN route has the potential to elicit strong mucosal and systemic immune responses in pigs. In this study, we evaluated the immune responses and cross-protective efficacy of IN chitosan encapsulated inactivated SwIAV vaccine in pigs. Killed SwIAV H1N2 (δ-lineage antigens (KAg were encapsulated in chitosan polymer-based nanoparticles (CNPs-KAg. The candidate vaccine was administered twice IN as mist to nursery pigs. Vaccinates and controls were then challenged with a zoonotic and virulent heterologous SwIAV H1N1 (γ-lineage. Pigs vaccinated with CNPs-KAg exhibited an enhanced IgG serum antibody and mucosal secretory IgA antibody responses in nasal swabs, bronchoalveolar lavage (BAL fluids, and lung lysates that were reactive against homologous (H1N2, heterologous (H1N1, and heterosubtypic (H3N2 influenza A virus strains. Prior to challenge, an increased frequency of cytotoxic T lymphocytes, antigen-specific lymphocyte proliferation, and recall IFN-γ secretion by restimulated peripheral blood mononuclear cells in CNPs-KAg compared to control KAg vaccinates were observed. In CNPs-KAg vaccinated pigs challenged with heterologous virus reduced severity of macroscopic and microscopic influenza-associated pulmonary lesions were observed. Importantly, the infectious SwIAV titers in nasal swabs [days post-challenge (DPC 4] and BAL fluid (DPC 6 were significantly (p < 0.05 reduced in CNPs-KAg vaccinates but not in KAg vaccinates when compared

  13. Effective inactivation of a wide range of viruses by pasteurization.

    Science.gov (United States)

    Gröner, Albrecht; Broumis, Connie; Fang, Randel; Nowak, Thomas; Popp, Birgit; Schäfer, Wolfram; Roth, Nathan J

    2018-01-01

    Careful selection and testing of plasma reduces the risk of blood-borne viruses in the starting material for plasma-derived products. Furthermore, effective measures such as pasteurization at 60°C for 10 hours have been implemented in the manufacturing process of therapeutic plasma proteins such as human albumin, coagulation factors, immunoglobulins, and enzyme inhibitors to inactivate blood-borne viruses of concern. A comprehensive compilation of the virus reduction capacity of pasteurization is presented including the effect of stabilizers used to protect the therapeutic protein from modifications during heat treatment. The virus inactivation kinetics of pasteurization for a broad range of viruses were evaluated in the relevant intermediates from more than 15 different plasma manufacturing processes. Studies were carried out under the routine manufacturing target variables, such as temperature and product-specific stabilizer composition. Additional studies were also performed under robustness conditions, that is, outside production specifications. The data demonstrate that pasteurization inactivates a wide range of enveloped and nonenveloped viruses of diverse physicochemical characteristics. After a maximum of 6 hours' incubation, no residual infectivity could be detected for the majority of enveloped viruses. Effective inactivation of a range of nonenveloped viruses, with the exception of nonhuman parvoviruses, was documented. Pasteurization is a very robust and reliable virus inactivation method with a broad effectiveness against known blood-borne pathogens and emerging or potentially emerging viruses. Pasteurization has proven itself to be a highly effective step, in combination with other complementary safety measures, toward assuring the virus safety of final product. © 2017 The Authors Transfusion published by Wiley Periodicals, Inc. on behalf of AABB.

  14. Human Phase 1 trial of low-dose inactivated seasonal influenza vaccine formulated with Advax™ delta inulin adjuvant.

    Science.gov (United States)

    Gordon, David L; Sajkov, Dimitar; Honda-Okubo, Yoshikazu; Wilks, Samuel H; Aban, Malet; Barr, Ian G; Petrovsky, Nikolai

    2016-07-19

    Influenza vaccines are usually non-adjuvanted but addition of adjuvant may improve immunogenicity and permit dose-sparing, critical for vaccine supply in the event of an influenza pandemic. The aim of this first-in-man study was to determine the effect of delta inulin adjuvant on the safety and immunogenicity of a reduced dose seasonal influenza vaccine. Healthy male and female adults aged 18-65years were recruited to participate in a randomized controlled study to compare the safety, tolerability and immunogenicity of a reduced-dose 2007 Southern Hemisphere trivalent inactivated influenza vaccine formulated with Advax™ delta inulin adjuvant (LTIV+Adj) when compared to a full-dose of the standard TIV vaccine which does not contain an adjuvant. LTIV+Adj provided equivalent immunogenicity to standard TIV vaccine as assessed by hemagglutination inhibition (HI) assays against each vaccine strain as well as against a number of heterosubtypic strains. HI responses were sustained at 3months post-immunisation in both groups. Antibody landscapes against a large panel of H3N2 influenza viruses showed distinct age effects whereby subjects over 40years old had a bimodal baseline HI distribution pattern, with the highest HI titers against the very oldest H3N2 isolates and with a second HI peak against influenza isolates from the last 5-10years. By contrast, subjects >40years had a unimodal baseline HI distribution with peak recognition of H3N2 isolates from approximately 20years ago. The reduced dose TIV vaccine containing Advax adjuvant was well tolerated and no safety issues were identified. Hence, delta inulin may be a useful adjuvant for use in seasonal or pandemic influenza vaccines. Australia New Zealand Clinical Trial Registry: ACTRN12607000599471. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Seasonal and pandemic human influenza viruses attach better to human upper respiratory tract epithelium than avian influenza viruses

    NARCIS (Netherlands)

    D.A.J. van Riel (Debby); M.A. den Bakker (Michael); L.M.E. Leijten (Lonneke); S. Chutinimitkul (Salin); V.J. Munster (Vincent); E. de Wit (Emmie); G.F. Rimmelzwaan (Guus); R.A.M. Fouchier (Ron); A.D.M.E. Osterhaus (Albert); T. Kuiken (Thijs)

    2010-01-01

    textabstractInfluenza viruses vary markedly in their efficiency of human-to-human transmission. This variation has been speculated to be determined in part by the tropism of influenza virus for the human upper respiratory tract. To study this tropism, we determined the pattern of virus attachment by

  16. Inactivation of viruses in labile blood derivatives. II. Physical methods

    International Nuclear Information System (INIS)

    Horowitz, B.; Wiebe, M.E.; Lippin, A.; Vandersande, J.; Stryker, M.H.

    1985-01-01

    The thermal inactivation of viruses in labile blood derivatives was evaluated by addition of marker viruses (VSV, Sindbis, Sendai, EMC) to anti-hemophilic factor (AHF) concentrates. The rate of virus inactivation at 60 degrees C was decreased by at least 100- to 700-fold by inclusion of 2.75 M glycine and 50 percent sucrose, or 3.0 M potassium citrate, additives which contribute to retention of protein biologic activity. Nonetheless, at least 10(4) infectious units of each virus was inactivated within 10 hours. Increasing the temperature from 60 to 70 or 80 degrees C caused a 90 percent or greater loss in AHF activity. An even greater decline in the rate of virus inactivation was observed on heating AHF in the lyophilized state, although no loss in AHF activity was observed after 72 hours of heating at 60 degrees C. Several of the proteins present in lyophilized AHF concentrates displayed an altered electrophoretic mobility as a result of exposure to 60 degrees C for 24 hours. Exposure of lyophilized AHF to irradiation from a cobalt 60 source resulted in an acceptable yield of AHF at 1.0, but not at 2.0, megarads. At 1 megarad, greater than or equal to 6.0 logs of VSV and 3.3 logs of Sindbis virus were inactivated

  17. Characterization of influenza virus among influenza like illness cases in Mumbai, India

    OpenAIRE

    Roy, Soumen; Dahake, Ritwik; Patil, Deepak; Tawde, Shweta; Mukherjee, Sandeepan; Athlekar, Shrikant; Chowdhary, Abhay; Deshmukh, Ranjana

    2014-01-01

    The present study was carried out to monitor influenza viruses by identifying the virus and studying the seasonal variation during 2007–2009 in Mumbai. A total of 193 clinical respiratory samples (nasal and throat swab) were collected from patients having influenza like illness in Mumbai region. One-step real-time reverse-transcriptase PCR (rRTPCR) was used to detect Influenza type A (H1 and H3) and Influenza type B virus. Isolation of the virus was carried out using in vitro system which was...

  18. Host adaptation and transmission of influenza A viruses in mammals

    Science.gov (United States)

    Schrauwen, Eefje JA; Fouchier, Ron AM

    2014-01-01

    A wide range of influenza A viruses of pigs and birds have infected humans in the last decade, sometimes with severe clinical consequences. Each of these so-called zoonotic infections provides an opportunity for virus adaptation to the new host. Fortunately, most of these human infections do not yield viruses with the ability of sustained human-to-human transmission. However, animal influenza viruses have acquired the ability of sustained transmission between humans to cause pandemics on rare occasions in the past, and therefore, influenza virus zoonoses continue to represent threats to public health. Numerous recent studies have shed new light on the mechanisms of adaptation and transmission of avian and swine influenza A viruses in mammals. In particular, several studies provided insights into the genetic and phenotypic traits of influenza A viruses that may determine airborne transmission. Here, we summarize recent studies on molecular determinants of virulence and adaptation of animal influenza A virus and discuss the phenotypic traits associated with airborne transmission of newly emerging influenza A viruses. Increased understanding of the determinants and mechanisms of virulence and transmission may aid in assessing the risks posed by animal influenza viruses to human health, and preparedness for such risks. PMID:26038511

  19. Aerosolized avian influenza virus by laboratory manipulations

    Directory of Open Access Journals (Sweden)

    Li Zhiping

    2012-08-01

    Full Text Available Abstract Background Avian H5N1 influenza viruses present a challenge in the laboratory environment, as they are difficult to collect from the air due to their small size and relatively low concentration. In an effort to generate effective methods of H5N1 air removal and ensure the safety of laboratory personnel, this study was designed to investigate the characteristics of aerosolized H5N1 produced by laboratory manipulations during research studies. Results Normal laboratory procedures used to process the influenza virus were carried out independently and the amount of virus polluting the on-site atmosphere was measured. In particular, zootomy, grinding, centrifugation, pipetting, magnetic stirring, egg inoculation, and experimental zoogenetic infection were performed. In addition, common accidents associated with each process were simulated, including breaking glass containers, syringe injection of influenza virus solution, and rupturing of centrifuge tubes. A micro-cluster sampling ambient air pollution collection device was used to collect air samples. The collected viruses were tested for activity by measuring their ability to induce hemagglutination with chicken red blood cells and to propagate in chicken embryos after direct inoculation, the latter being detected by reverse-transcription PCR and HA test. The results showed that the air samples from the normal centrifugal group and the negative-control group were negative, while all other groups were positive for H5N1. Conclusions Our findings suggest that there are numerous sources of aerosols in laboratory operations involving H5N1. Thus, laboratory personnel should be aware of the exposure risk that accompanies routine procedures involved in H5N1 processing and take proactive measures to prevent accidental infection and decrease the risk of virus aerosol leakage beyond the laboratory.

  20. Aerosolized avian influenza virus by laboratory manipulations.

    Science.gov (United States)

    Li, Zhiping; Li, Jinsong; Zhang, Yandong; Li, Lin; Ma, Limin; Li, Dan; Gao, Feng; Xia, Zhiping

    2012-08-06

    Avian H5N1 influenza viruses present a challenge in the laboratory environment, as they are difficult to collect from the air due to their small size and relatively low concentration. In an effort to generate effective methods of H5N1 air removal and ensure the safety of laboratory personnel, this study was designed to investigate the characteristics of aerosolized H5N1 produced by laboratory manipulations during research studies. Normal laboratory procedures used to process the influenza virus were carried out independently and the amount of virus polluting the on-site atmosphere was measured. In particular, zootomy, grinding, centrifugation, pipetting, magnetic stirring, egg inoculation, and experimental zoogenetic infection were performed. In addition, common accidents associated with each process were simulated, including breaking glass containers, syringe injection of influenza virus solution, and rupturing of centrifuge tubes. A micro-cluster sampling ambient air pollution collection device was used to collect air samples. The collected viruses were tested for activity by measuring their ability to induce hemagglutination with chicken red blood cells and to propagate in chicken embryos after direct inoculation, the latter being detected by reverse-transcription PCR and HA test. The results showed that the air samples from the normal centrifugal group and the negative-control group were negative, while all other groups were positive for H5N1. Our findings suggest that there are numerous sources of aerosols in laboratory operations involving H5N1. Thus, laboratory personnel should be aware of the exposure risk that accompanies routine procedures involved in H5N1 processing and take proactive measures to prevent accidental infection and decrease the risk of virus aerosol leakage beyond the laboratory.

  1. Development of methods to measure virus inactivation in fresh waters.

    OpenAIRE

    Ward, R L; Winston, P E

    1985-01-01

    This study concerns the identification and correction of deficiencies in methods used to measure inactivation rates of enteric viruses seeded into environmental waters. It was found that viable microorganisms in an environmental water sample increased greatly after addition of small amounts of nutrients normally present in the unpurified seed virus preparation. This burst of microbial growth was not observed after seeding the water with purified virus. The use of radioactively labeled poliovi...

  2. Characterization of uncultivable bat influenza virus using a replicative synthetic virus.

    Directory of Open Access Journals (Sweden)

    Bin Zhou

    2014-10-01

    Full Text Available Bats harbor many viruses, which are periodically transmitted to humans resulting in outbreaks of disease (e.g., Ebola, SARS-CoV. Recently, influenza virus-like sequences were identified in bats; however, the viruses could not be cultured. This discovery aroused great interest in understanding the evolutionary history and pandemic potential of bat-influenza. Using synthetic genomics, we were unable to rescue the wild type bat virus, but could rescue a modified bat-influenza virus that had the HA and NA coding regions replaced with those of A/PR/8/1934 (H1N1. This modified bat-influenza virus replicated efficiently in vitro and in mice, resulting in severe disease. Additional studies using a bat-influenza virus that had the HA and NA of A/swine/Texas/4199-2/1998 (H3N2 showed that the PR8 HA and NA contributed to the pathogenicity in mice. Unlike other influenza viruses, engineering truncations hypothesized to reduce interferon antagonism into the NS1 protein didn't attenuate bat-influenza. In contrast, substitution of a putative virulence mutation from the bat-influenza PB2 significantly attenuated the virus in mice and introduction of a putative virulence mutation increased its pathogenicity. Mini-genome replication studies and virus reassortment experiments demonstrated that bat-influenza has very limited genetic and protein compatibility with Type A or Type B influenza viruses, yet it readily reassorts with another divergent bat-influenza virus, suggesting that the bat-influenza lineage may represent a new Genus/Species within the Orthomyxoviridae family. Collectively, our data indicate that the bat-influenza viruses recently identified are authentic viruses that pose little, if any, pandemic threat to humans; however, they provide new insights into the evolution and basic biology of influenza viruses.

  3. Characterization of uncultivable bat influenza virus using a replicative synthetic virus.

    Science.gov (United States)

    Zhou, Bin; Ma, Jingjiao; Liu, Qinfang; Bawa, Bhupinder; Wang, Wei; Shabman, Reed S; Duff, Michael; Lee, Jinhwa; Lang, Yuekun; Cao, Nan; Nagy, Abdou; Lin, Xudong; Stockwell, Timothy B; Richt, Juergen A; Wentworth, David E; Ma, Wenjun

    2014-10-01

    Bats harbor many viruses, which are periodically transmitted to humans resulting in outbreaks of disease (e.g., Ebola, SARS-CoV). Recently, influenza virus-like sequences were identified in bats; however, the viruses could not be cultured. This discovery aroused great interest in understanding the evolutionary history and pandemic potential of bat-influenza. Using synthetic genomics, we were unable to rescue the wild type bat virus, but could rescue a modified bat-influenza virus that had the HA and NA coding regions replaced with those of A/PR/8/1934 (H1N1). This modified bat-influenza virus replicated efficiently in vitro and in mice, resulting in severe disease. Additional studies using a bat-influenza virus that had the HA and NA of A/swine/Texas/4199-2/1998 (H3N2) showed that the PR8 HA and NA contributed to the pathogenicity in mice. Unlike other influenza viruses, engineering truncations hypothesized to reduce interferon antagonism into the NS1 protein didn't attenuate bat-influenza. In contrast, substitution of a putative virulence mutation from the bat-influenza PB2 significantly attenuated the virus in mice and introduction of a putative virulence mutation increased its pathogenicity. Mini-genome replication studies and virus reassortment experiments demonstrated that bat-influenza has very limited genetic and protein compatibility with Type A or Type B influenza viruses, yet it readily reassorts with another divergent bat-influenza virus, suggesting that the bat-influenza lineage may represent a new Genus/Species within the Orthomyxoviridae family. Collectively, our data indicate that the bat-influenza viruses recently identified are authentic viruses that pose little, if any, pandemic threat to humans; however, they provide new insights into the evolution and basic biology of influenza viruses.

  4. The public health impact of avian influenza viruses.

    Science.gov (United States)

    Katz, J M; Veguilla, V; Belser, J A; Maines, T R; Van Hoeven, N; Pappas, C; Hancock, K; Tumpey, T M

    2009-04-01

    Influenza viruses with novel hemagglutinin and 1 or more accompanying genes derived from avian influenza viruses sporadically emerge in humans and have the potential to result in a pandemic if the virus causes disease and spreads efficiently in a population that lacks immunity to the novel hemagglutinin. Since 1997, multiple avian influenza virus subtypes have been transmitted directly from domestic poultry to humans and have caused a spectrum of human disease, from asymptomatic to severe and fatal. To assess the pandemic risk that avian influenza viruses pose, we have used multiple strategies to better understand the capacity of avian viruses to infect, cause disease, and transmit among mammals, including humans. Seroepidemiologic studies that evaluate the frequency and risk of human infection with avian influenza viruses in populations with exposure to domestic or wild birds can provide a better understanding of the pandemic potential of avian influenza subtypes. Investigations conducted in Hong Kong following the first H5N1 outbreak in humans in 1997 determined that exposure to poultry in live bird markets was a key risk factor for human disease. Among poultry workers, butchering and exposure to sick poultry were risk factors for antibody to H5 virus, which provided evidence for infection. A second risk assessment tool, the ferret, can be used to evaluate the level of virulence and potential for host-to-host transmission of avian influenza viruses in this naturally susceptible host. Avian viruses isolated from humans exhibit a level of virulence and transmissibility in ferrets that generally reflects that seen in humans. The ferret model thus provides a means to monitor emerging avian influenza viruses for pandemic risk, as well as to evaluate laboratory-generated reassortants and mutants to better understand the molecular basis of influenza virus transmissibility. Taken together, such studies provide valuable information with which we can assess the public

  5. Mucosal Immunity and Protective Efficacy of Intranasal Inactivated Influenza Vaccine Is Improved by Chitosan Nanoparticle Delivery in Pigs.

    Science.gov (United States)

    Dhakal, Santosh; Renu, Sankar; Ghimire, Shristi; Shaan Lakshmanappa, Yashavanth; Hogshead, Bradley T; Feliciano-Ruiz, Ninoshkaly; Lu, Fangjia; HogenEsch, Harm; Krakowka, Steven; Lee, Chang Won; Renukaradhya, Gourapura J

    2018-01-01

    Annually, swine influenza A virus (SwIAV) causes severe economic loss to swine industry. Currently used inactivated SwIAV vaccines administered by intramuscular injection provide homologous protection, but limited heterologous protection against constantly evolving field viruses, attributable to the induction of inadequate levels of mucosal IgA and cellular immune responses in the respiratory tract. A novel vaccine delivery platform using mucoadhesive chitosan nanoparticles (CNPs) administered through intranasal (IN) route has the potential to elicit strong mucosal and systemic immune responses in pigs. In this study, we evaluated the immune responses and cross-protective efficacy of IN chitosan encapsulated inactivated SwIAV vaccine in pigs. Killed SwIAV H1N2 (δ-lineage) antigens (KAg) were encapsulated in chitosan polymer-based nanoparticles (CNPs-KAg). The candidate vaccine was administered twice IN as mist to nursery pigs. Vaccinates and controls were then challenged with a zoonotic and virulent heterologous SwIAV H1N1 (γ-lineage). Pigs vaccinated with CNPs-KAg exhibited an enhanced IgG serum antibody and mucosal secretory IgA antibody responses in nasal swabs, bronchoalveolar lavage (BAL) fluids, and lung lysates that were reactive against homologous (H1N2), heterologous (H1N1), and heterosubtypic (H3N2) influenza A virus strains. Prior to challenge, an increased frequency of cytotoxic T lymphocytes, antigen-specific lymphocyte proliferation, and recall IFN-γ secretion by restimulated peripheral blood mononuclear cells in CNPs-KAg compared to control KAg vaccinates were observed. In CNPs-KAg vaccinated pigs challenged with heterologous virus reduced severity of macroscopic and microscopic influenza-associated pulmonary lesions were observed. Importantly, the infectious SwIAV titers in nasal swabs [days post-challenge (DPC) 4] and BAL fluid (DPC 6) were significantly ( p  influenza nanovaccine may be an ideal candidate vaccine for use in pigs, and pig is a

  6. Characterization of Seasonal Influenza Virus Type and Subtypes Isolated from Influenza Like Illness Cases of 2012.

    Science.gov (United States)

    Upadhyay, B P; Ghimire, P; Tashiro, M; Banjara, M R

    Background Seasonal influenza is one of the increasing public health burdens in Nepal. Objective The objective of this study was to isolate and characterize the influenza virus type and subtypes of Nepal. Method A total of 1536 throat swab specimens were collected from January to December 2012. Total ribonucleic acid was extracted using Qiagen viral nucleic acid extraction kit and polymerase chain reaction assay was performed following the US; CDC Real-time PCR protocol. Ten percent of positive specimens were inoculated onto Madin-Darby Canine Kidney cells. Isolates were characterized by using reference ferret antisera. Result Of the total specimens (n=1536), influenza virus type A was detected in 196 (22%) cases; of which 194 (99%) were influenza A (H1N1) pdm09 and 2 (1 %) were influenza A/H3 subtype. Influenza B was detected in 684 (76.9%) cases. Influenza A (H1N1) pdm09, A/H3 and influenza B virus were antigenically similar to the recommended influenza virus vaccine candidate of the year 2012. Although sporadic cases of influenza were observed throughout the year, peak was observed during July to November. Conclusion Similar to other tropical countries, A (H1N1) pdm09, A/H3 and influenza B viruses were co-circulated in Nepal.

  7. MicroRNA-Based Attenuation of Influenza Virus across Susceptible Hosts.

    Science.gov (United States)

    Waring, Barbara M; Sjaastad, Louisa E; Fiege, Jessica K; Fay, Elizabeth J; Reyes, Ismarc; Moriarity, Branden; Langlois, Ryan A

    2018-01-15

    Influenza A virus drives significant morbidity and mortality in humans and livestock. Annual circulation of the virus in livestock and waterfowl contributes to severe economic disruption and increases the risk of zoonotic transmission of novel strains into the human population, where there is no preexisting immunity. Seasonal vaccinations in humans help prevent infection and can reduce symptoms when infection does occur. However, current vaccination regimens available for livestock are limited in part due to safety concerns regarding reassortment/recombination with circulating strains. Therefore, inactivated vaccines are used instead of the more immunostimulatory live attenuated vaccines. MicroRNAs (miRNAs) have been used previously to generate attenuated influenza A viruses for use as a vaccine. Here, we systematically targeted individual influenza gene mRNAs using the same miRNA to determine the segment(s) that yields maximal attenuation potential. This analysis demonstrated that targeting of NP mRNA most efficiently ablates replication. We further increased the plasticity of miRNA-mediated attenuation of influenza A virus by exploiting a miRNA, miR-21, that is ubiquitously expressed across influenza-susceptible hosts. In order to construct this targeted virus, we used CRISPR/Cas9 to eliminate the universally expressed miR-21 from MDCK cells. miR-21-targeted viruses were attenuated in human, mouse, canine, and avian cells and drove protective immunity in mice. This strategy has the potential to enhance the safety of live attenuated vaccines in humans and zoonotic reservoirs. IMPORTANCE Influenza A virus circulates annually in both avian and human populations, causing significant morbidity, mortality, and economic burden. High incidence of zoonotic infections greatly increases the potential for transmission to humans, where no preexisting immunity or vaccine exists. There is a critical need for new vaccine strategies to combat emerging influenza outbreaks. Micro

  8. Prevention and Treatment of Avian Influenza A Viruses in People

    Science.gov (United States)

    ... and Treatment of Avian Influenza A Viruses in People Language: English (US) Español Recommend on Facebook Tweet ... can happen when enough virus gets into a person’s eyes, nose or mouth, or is inhaled. This ...

  9. Preparation of mucosal nanoparticles and polymer-based inactivated vaccine for Newcastle disease and H9N2 AI viruses

    Directory of Open Access Journals (Sweden)

    Heba M. El Naggar

    2017-02-01

    Full Text Available Aim: To develop a mucosal inactivated vaccines for Newcastle disease (ND and H9N2 viruses to protect against these viruses at sites of infections through mucosal immunity. Materials and Methods: In this study, we prepared two new formulations for mucosal bivalent inactivated vaccine formulations for Newcastle and Avian Influenza (H9N2 based on the use of nanoparticles and polymer adjuvants. The prepared vaccines were delivered via intranasal and spray routes of administration in specific pathogen-free chickens. Cell-mediated and humoral immune response was measured as well as challenge trial was carried out. In addition, ISA71 water in oil was also evaluated. Results: Our results showed that the use of spray route as vaccination delivery method of polymer and nanoparticles MontanideTM adjuvants revealed that it enhanced the cell mediated immune response as indicated by phagocytic activity, gamma interferon and interleukin 6 responses and induced protection against challenge with Newcastle and Avian Influenza (H9N2 viruses. Conclusion: The results of this study demonstrate the potentiality of polymer compared to nanoparticles adjuvantes when used via spray route. Mass application of such vaccines will add value to improve the vaccination strategies against ND virus and Avian influenza viruses.

  10. Studies on disappearance and inactivation of viruses in sewage, 2

    International Nuclear Information System (INIS)

    Yano, Kazuyoshi; Yabuuchi, Kiyoshi; Taguchi, Fumiaki.

    1985-01-01

    Methods of inactivating viruses in wastewater were studied. Polio visuses were added to the distilled water until the number of viruses reached 10sup(6.8) TCID 50 /ml, and liquid layer was 2 mm. The inactivation rate of viruses was determined at each time of ultraviolet (U.V.) irradiation (from 0.425 x 10 4 μw/cm 2 to 10.0 x 10 4 μw/cm 2 ). A linear correlation was seen between the inactivation rate of viruses and the time of U.V. irradiation obtained from logarithmic transformation. The irradiation time required for inactivation of 99.9% viruses was 15 sec when U.V. intensity was 10.0 x 10 4 μw/cm 2 and 9.6 min when it was 0.423 x 10 4 μw/cm 2 . When the U.V. intensity was 0.425 x 10 4 μw/cm 2 , the time required for inactivation was dependent on the number of viruses (120 sec in cases of 10sup(3.8) TCID 50 /ml of viruses and 720 sec in cases of 10sup(7.8) TCID 50 /ml of viruses). When viruses were added to the distilled water until the number reached 10sup(5.8) TCID 50 /ml, and the depth of water was designated as 2 mm, 10 cm, and 15 cm, the U.V. permeability was more than 89% at any depth of water, and a sixteen-min U.V. irradiation inactivated more than 99.99% of viruses. When polio viruses were added to triple step-treated water until the number reached 10sup(5.3) TCID 50 /ml, the irradiation time required for inactivation of more than 99.99% was one min when the U.V. intensity was 10.0 x 10 4 μw/cm 2 and 20 min when it was 0.425 x 10 4 μw/cm 2 . (Namekawa, K.)

  11. Inactivation of viruses in municipal effluent by chlorine.

    OpenAIRE

    Hajenian, H. G.; Butler, M.

    1980-01-01

    The influence of pH and temperature on the efficiency of chlorine inactivation of two unrelated picornaviruses in a typical urban wastewater effluent was examined. Temperature, unlike pH, had relatively little effect on the rate of inactivation. The pH effect was complex and the two viruses differed. The f2 coliphage was more sensitive to chlorine at low pH, but at all values there was a threshold above which additional chlorine resulted in very rapid inactivation. The amount of chlorine requ...

  12. Characterization of influenza virus among influenza like illness cases in Mumbai, India.

    Science.gov (United States)

    Roy, Soumen; Dahake, Ritwik; Patil, Deepak; Tawde, Shweta; Mukherjee, Sandeepan; Athlekar, Shrikant; Chowdhary, Abhay; Deshmukh, Ranjana

    2014-01-01

    The present study was carried out to monitor influenza viruses by identifying the virus and studying the seasonal variation during 2007-2009 in Mumbai. A total of 193 clinical respiratory samples (nasal and throat swab) were collected from patients having influenza like illness in Mumbai region. One-step real-time reverse-transcriptase PCR (rRTPCR) was used to detect Influenza type A (H1 and H3) and Influenza type B virus. Isolation of the virus was carried out using in vitro system which was further confirmed and typed by hemagglutination assay and hemagglutination inhibition assay. Out of 193 samples 24 (12.4 3%) samples tested positive for influenza virus, of which 13 (6.73 %) were influenza type A virus and 10 (5.18 %) were influenza type B virus, while 1 sample (0.51 %) was positive for both. By culture methods, 3 (1.55 %) viral isolates were obtained. All the three isolates were found to be Influenza type B/Malaysia (Victoria lineage) by Hemagglutination Inhibition Assay. The data generated from the present study reveals that both Influenza type A and B are prevalent in Mumbai with considerable activity. The peak activity was observed during monsoon season.

  13. New world bats harbor diverse influenza A viruses.

    Directory of Open Access Journals (Sweden)

    Suxiang Tong

    Full Text Available Aquatic birds harbor diverse influenza A viruses and are a major viral reservoir in nature. The recent discovery of influenza viruses of a new H17N10 subtype in Central American fruit bats suggests that other New World species may similarly carry divergent influenza viruses. Using consensus degenerate RT-PCR, we identified a novel influenza A virus, designated as H18N11, in a flat-faced fruit bat (Artibeus planirostris from Peru. Serologic studies with the recombinant H18 protein indicated that several Peruvian bat species were infected by this virus. Phylogenetic analyses demonstrate that, in some gene segments, New World bats harbor more influenza virus genetic diversity than all other mammalian and avian species combined, indicative of a long-standing host-virus association. Structural and functional analyses of the hemagglutinin and neuraminidase indicate that sialic acid is not a ligand for virus attachment nor a substrate for release, suggesting a unique mode of influenza A virus attachment and activation of membrane fusion for entry into host cells. Taken together, these findings indicate that bats constitute a potentially important and likely ancient reservoir for a diverse pool of influenza viruses.

  14. Flock-based surveillance for lowpathogenic avian influenza virus in ...

    African Journals Online (AJOL)

    Flock-based surveillance for lowpathogenic avian influenza virus in commercial breeders and layers, southwest Nigeria. ... African Journal of Infectious Diseases ... Background: Flock surveillance systems for avian influenza (AI) virus play a critical role in countries where vaccination is not practiced so as to establish the ...

  15. Xanthones from Polygala karensium inhibit neuraminidases from influenza A viruses

    DEFF Research Database (Denmark)

    Dao, Trong Tuan; Dang, Thai Trung; Nguyen, Phi Hung

    2012-01-01

    The emergence of the H1N1 swine flu pandemic has the possibility to develop the occurrence of disaster- or drug-resistant viruses by additional reassortments in novel influenza A virus. In the course of an anti-influenza screening program for natural products, 10 xanthone derivatives (1-10) were ...

  16. radioprotective and interferonogenic characteristics of influenza virus vaccine

    International Nuclear Information System (INIS)

    Ivanov, A.A.; Ershov, F.I.; Ulanova, A.M.; Kuz'mina, T.D.; Stavrakova, N.M.; Tazulakhova, Eh.B.; Shal'nova, G.A.; Akademiya Meditsinskikh Nauk SSSR, Moscow

    1995-01-01

    Different methods of prophylactic treatment with influenza virus vaccina increase survival of irradiated mice and hamsters by 25-55% as compared to unprotected ones. Higher radioresistance occurs in the same time intervals as a rise of interferon in the blood after immunization with influenza virus vaccine. 7 refs.; 2 figs.; 2 tabs

  17. Detecting emerging transmissibility of avian influenza virus in human households

    NARCIS (Netherlands)

    Boven, M. van; Koopmans, M.; Du Ry van Beest Holle, M.; Meijer, Adam; Klinkenberg, D.; Donnelly, C.A.; Heesterbeek, J.A.P.

    Accumulating infections of highly pathogenic H5N1 avian influenza in humans underlines the need to track the ability of these viruses to spread among humans. A human-transmissible avian influenza virus is expected to cause clusters of infections in humans living in close contact. Therefore,

  18. Detecting emerging transmissibility of avian influenza virus in human households

    NARCIS (Netherlands)

    Boven, van R.M.; Koopmans, M.; Du Ry Beest Holle, van M.; Meijer, A.; Klinkenberg, D.; Donnelly, C.; Heesterbeek, J.A.P.

    2007-01-01

    Accumulating infections of highly pathogenic H5N1 avian influenza in humans underlines the need to track the ability of these viruses to spread among humans. A human-transmissible avian influenza virus is expected to cause clusters of infections in humans living in close contact. Therefore,

  19. Predicting Hotspots for Influenza Virus Reassortment

    Science.gov (United States)

    Gilbert, Marius; Martin, Vincent; Cappelle, Julien; Hosseini, Parviez; Njabo, Kevin Y.; Abdel Aziz, Soad; Xiao, Xiangming; Daszak, Peter; Smith, Thomas B.

    2013-01-01

    The 1957 and 1968 influenza pandemics, each of which killed ≈1 million persons, arose through reassortment events. Influenza virus in humans and domestic animals could reassort and cause another pandemic. To identify geographic areas where agricultural production systems are conducive to reassortment, we fitted multivariate regression models to surveillance data on influenza A virus subtype H5N1 among poultry in China and Egypt and subtype H3N2 among humans. We then applied the models across Asia and Egypt to predict where subtype H3N2 from humans and subtype H5N1 from birds overlap; this overlap serves as a proxy for co-infection and in vivo reassortment. For Asia, we refined the prioritization by identifying areas that also have high swine density. Potential geographic foci of reassortment include the northern plains of India, coastal and central provinces of China, the western Korean Peninsula and southwestern Japan in Asia, and the Nile Delta in Egypt. PMID:23628436

  20. Genetic characterization of highly pathogenic avian influenza A H5N8 viruses isolated from wild birds in Egypt.

    Science.gov (United States)

    Kandeil, Ahmed; Kayed, Ahmed; Moatasim, Yassmin; Webby, Richard J; McKenzie, Pamela P; Kayali, Ghazi; Ali, Mohamed A

    2017-07-01

    A newly emerged H5N8 influenza virus was isolated from green-winged teal in Egypt during December 2016. In this study, we provide a detailed characterization of full genomes of Egyptian H5N8 viruses and some virological features. Genetic analysis demonstrated that the Egyptian H5N8 viruses are highly pathogenic avian influenza viruses. Phylogenetic analysis revealed that the genome of the Egyptian H5N8 viruses was related to recently characterized reassortant H5N8 viruses of clade 2.3.4.4 isolated from different Eurasian countries. Multiple peculiar mutations were characterized in the Egyptian H5N8 viruses, which probably permits transmission and virulence of these viruses in mammals. The Egyptian H5N8 viruses preferentially bound to avian-like receptors rather than human-like receptors. Also, the Egyptian H5N8 viruses were fully sensitive to amantadine and neuraminidase inhibitors. Chicken sera raised against commercial inactivated avian influenza-H5 vaccines showed no or very low reactivity with the currently characterized H5N8 viruses in agreement with the genetic dissimilarity. Surveillance of avian influenza in waterfowl provides early warning of specific threats to poultry and human health and hence should be continued.

  1. No serological evidence that harbour porpoises are additional hosts of influenza B viruses

    NARCIS (Netherlands)

    R. Bodewes (Rogier); M.W.G. van de Bildt (Marco); C.E. van Elk; P.E. Bunskoek (Paulien); D.A.M.C. van de Vijver (David); S.L. Smits (Saskia); A.D.M.E. Osterhaus (Albert); T. Kuiken (Thijs)

    2014-01-01

    textabstractInfluenza A and B viruses circulate among humans causing epidemics almost annually. While various hosts for influenza A viruses exist, influenza B viruses have been detected only in humans and seals. However, recurrent infections of seals in Dutch coastal waters with influenza B viruses

  2. Molecular Determinants of Influenza Virus Pathogenesis in Mice

    Science.gov (United States)

    Katz, Jaqueline M.; York, Ian A.

    2015-01-01

    Mice are widely used for studying influenza virus pathogenesis and immunology because of their low cost, the wide availability of mouse-specific reagents, and the large number of mouse strains available, including knockout and transgenic strains. However, mice do not fully recapitulate the signs of influenza infection of humans: transmission of influenza between mice is much less efficient than in humans, and influenza viruses often require adaptation before they are able to efficiently replicate in mice. In the process of mouse adaptation, influenza viruses acquire mutations that enhance their ability to attach to mouse cells, replicate within the cells, and suppress immunity, among other functions. Many such mouse-adaptive mutations have been identified, covering all 8 genomic segments of the virus. Identification and analysis of these mutations have provided insight into the molecular determinants of influenza virulence and pathogenesis, not only in mice but also in humans and other species. In particular, several mouse-adaptive mutations of avian influenza viruses have proved to be general mammalian-adaptive changes that are potential markers of pre-pandemic viruses. As well as evaluating influenza pathogenesis, mice have also been used as models for evaluation of novel vaccines and anti-viral therapies. Mice can be a useful animal model for studying influenza biology as long as differences between human and mice infections are taken into account. PMID:25038937

  3. Immunomodulatory Activity of Red Ginseng against Influenza A Virus Infection

    Directory of Open Access Journals (Sweden)

    Jong Seok Lee

    2014-01-01

    Full Text Available Ginseng herbal medicine has been known to have beneficial effects on improving human health. We investigated whether red ginseng extract (RGE has preventive effects on influenza A virus infection in vivo and in vitro. RGE was found to improve survival of human lung epithelial cells upon influenza virus infection. Also, RGE treatment reduced the expression of pro-inflammatory genes (IL-6, IL-8 probably in part through interference with the formation of reactive oxygen species by influenza A virus infection. Long-term oral administration of mice with RGE showed multiple immunomodulatory effects such as stimulating antiviral cytokine IFN-γ production after influenza A virus infection. In addition, RGE administration in mice inhibited the infiltration of inflammatory cells into the bronchial lumens. Therefore, RGE might have the potential beneficial effects on preventing influenza A virus infections via its multiple immunomodulatory functions.

  4. Mucosal immune response in broilers following vaccination with inactivated influenza and recombinant Bacillus subtilis

    Science.gov (United States)

    Mucosal and systemic immunity were observed in broilers vaccinated with mannosylated chitosan adjuvated (MCA) inactivated A/Turkey/Virginia/158512/2002 (H7N2) and administered with and without recombinant Bacillus subtilis to elicit heterologous influenza strain protection. Previously, mucosal immu...

  5. Influenza virus induces apoptosis via BAD-mediated mitochondrial dysregulation.

    Science.gov (United States)

    Tran, Anh T; Cortens, John P; Du, Qiujiang; Wilkins, John A; Coombs, Kevin M

    2013-01-01

    Influenza virus infection results in host cell death and major tissue damage. Specific components of the apoptotic pathway, a signaling cascade that ultimately leads to cell death, are implicated in promoting influenza virus replication. BAD is a cell death regulator that constitutes a critical control point in the intrinsic apoptosis pathway, which occurs through the dysregulation of mitochondrial outer membrane permeabilization and the subsequent activation of downstream apoptogenic factors. Here we report a novel proviral role for the proapoptotic protein BAD in influenza virus replication. We show that influenza virus-induced cytopathology and cell death are considerably inhibited in BAD knockdown cells and that both virus replication and viral protein production are dramatically reduced, which suggests that virus-induced apoptosis is BAD dependent. Our data showed that influenza viruses induced phosphorylation of BAD at residues S112 and S136 in a temporal manner. Viral infection also induced BAD cleavage, late in the viral life cycle, to a truncated form that is reportedly a more potent inducer of apoptosis. We further demonstrate that knockdown of BAD resulted in reduced cytochrome c release and suppression of the intrinsic apoptotic pathway during influenza virus replication, as seen by an inhibition of caspases-3, caspase-7, and procyclic acidic repetitive protein (PARP) cleavage. Our data indicate that influenza viruses carefully modulate the activation of the apoptotic pathway that is dependent on the regulatory function of BAD and that failure of apoptosis activation resulted in unproductive viral replication.

  6. The Mutational Robustness of Influenza A Virus.

    Directory of Open Access Journals (Sweden)

    Elisa Visher

    2016-08-01

    Full Text Available A virus' mutational robustness is described in terms of the strength and distribution of the mutational fitness effects, or MFE. The distribution of MFE is central to many questions in evolutionary theory and is a key parameter in models of molecular evolution. Here we define the mutational fitness effects in influenza A virus by generating 128 viruses, each with a single nucleotide mutation. In contrast to mutational scanning approaches, this strategy allowed us to unambiguously assign fitness values to individual mutations. The presence of each desired mutation and the absence of additional mutations were verified by next generation sequencing of each stock. A mutation was considered lethal only after we failed to rescue virus in three independent transfections. We measured the fitness of each viable mutant relative to the wild type by quantitative RT-PCR following direct competition on A549 cells. We found that 31.6% of the mutations in the genome-wide dataset were lethal and that the lethal fraction did not differ appreciably between the HA- and NA-encoding segments and the rest of the genome. Of the viable mutants, the fitness mean and standard deviation were 0.80 and 0.22 in the genome-wide dataset and best modeled as a beta distribution. The fitness impact of mutation was marginally lower in the segments coding for HA and NA (0.88 ± 0.16 than in the other 6 segments (0.78 ± 0.24, and their respective beta distributions had slightly different shape parameters. The results for influenza A virus are remarkably similar to our own analysis of CirSeq-derived fitness values from poliovirus and previously published data from other small, single stranded DNA and RNA viruses. These data suggest that genome size, and not nucleic acid type or mode of replication, is the main determinant of viral mutational fitness effects.

  7. The effectiveness of seasonal trivalent inactivated influenza vaccine in preventing laboratory confirmed influenza hospitalisations in Auckland, New Zealand in 2012.

    Science.gov (United States)

    Turner, Nikki; Pierse, Nevil; Bissielo, Ange; Huang, Q Sue; Baker, Michael G; Widdowson, Marc-Alain; Kelly, Heath

    2014-06-17

    Few studies report the effectiveness of trivalent inactivated influenza vaccine (TIV) in preventing hospitalisation for influenza-confirmed respiratory infections. Using a prospective surveillance platform, this study reports the first such estimate from a well-defined ethnically diverse population in New Zealand (NZ). A case test-negative design was used to estimate propensity adjusted vaccine effectiveness. Patients with a severe acute respiratory infection (SARI), defined as a patient of any age requiring hospitalisation with a history of a fever or a measured temperature ≥38°C and cough and onset within the past 7 days, admitted to public hospitals in South and Central Auckland were eligible for inclusion in the study. Cases were SARI patients who tested positive for influenza, while non-cases (controls) were SARI patients who tested negative. Results were adjusted for the propensity to be vaccinated and the timing of the influenza season. The propensity and season adjusted vaccine effectiveness (VE) was estimated as 39% (95% CI 16;56). The VE point estimate against influenza A (H1N1) was lower than for influenza B or influenza A (H3N2) but confidence intervals were wide and overlapping. Estimated VE was 59% (95% CI 26;77) in patients aged 45-64 years but only 8% (-78;53) in those aged 65 years and above. Prospective surveillance for SARI has been successfully established in NZ. This study for the first year, the 2012 influenza season, has shown low to moderate protection by TIV against influenza positive hospitalisation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. The effectiveness of seasonal trivalent inactivated influenza vaccine in preventing laboratory confirmed influenza hospitalisations in Auckland, New Zealand in 2012

    Science.gov (United States)

    Turner, Nikki; Pierse, Nevil; Bissielo, Ange; Huang, Q Sue; Baker, Michael; Widdowson, Marc-Alain; Kelly, Heath

    2015-01-01

    Background Few studies report the effectiveness of trivalent inactivated influenza vaccine (TIV) in preventing hospitalisation for influenza-confirmed respiratory infections. Using a prospective surveillance platform, this study reports the first such estimate from a well-defined ethnically diverse population in New Zealand (NZ). Methods A case test-negative study was used to estimate propensity adjusted vaccine effectiveness. Patients with a severe acute respiratory infection (SARI), defined as a patient of any age requiring hospitalization with a history of a fever or a measured temperature ≥38°C and cough and onset within the past 7 days, admitted to public hospitals in Central, South and East Auckland were eligible for inclusion in the study. Cases were SARI patients who tested positive for influenza, while non-cases (controls) were SARI patients who tested negative. Results were adjusted for the propensity to be vaccinated and the timing of the influenza season Results The propensity and season adjusted vaccine effectiveness (VE) was estimated as 37% (95% CI 18;51). The VE point estimate against influenza A (H1N1) was higher than for influenza B or influenza A (H3N2) but confidence intervals were wide and overlapping. Estimated VE was 51% (95% CI 28;67) in patients aged 18-64 years but only 6% (95% CI -51;42) in those aged 65 years and above. Conclusion Prospective surveillance for SARI has been successfully established in NZ . This study for the first year, the 2012 influenza season, has shown low to moderate protection by TIV against hospitalisation for laboratory-confirmed influenza. PMID:24768730

  9. Influenza A and B Virus Intertypic Reassortment through Compatible Viral Packaging Signals

    Science.gov (United States)

    Baker, Steven F.; Nogales, Aitor; Finch, Courtney; Tuffy, Kevin M.; Domm, William; Perez, Daniel R.; Topham, David J.

    2014-01-01

    ABSTRACT Influenza A and B viruses cocirculate in humans and together cause disease and seasonal epidemics. These two types of influenza viruses are evolutionarily divergent, and exchange of genetic segments inside coinfected cells occurs frequently within types but never between influenza A and B viruses. Possible mechanisms inhibiting the intertypic reassortment of genetic segments could be due to incompatible protein functions of segment homologs, a lack of processing of heterotypic segments by influenza virus RNA-dependent RNA polymerase, an inhibitory effect of viral proteins on heterotypic virus function, or an inability to specifically incorporate heterotypic segments into budding virions. Here, we demonstrate that the full-length hemagglutinin (HA) of prototype influenza B viruses can complement the function of multiple influenza A viruses. We show that viral noncoding regions were sufficient to drive gene expression for either type A or B influenza virus with its cognate or heterotypic polymerase. The native influenza B virus HA segment could not be incorporated into influenza A virus virions. However, by adding the influenza A virus packaging signals to full-length influenza B virus glycoproteins, we rescued influenza A viruses that possessed HA, NA, or both HA and NA of influenza B virus. Furthermore, we show that, similar to single-cycle infectious influenza A virus, influenza B virus cannot incorporate heterotypic transgenes due to packaging signal incompatibilities. Altogether, these results demonstrate that the lack of influenza A and B virus reassortants can be attributed at least in part to incompatibilities in the virus-specific packaging signals required for effective segment incorporation into nascent virions. IMPORTANCE Reassortment of influenza A or B viruses provides an evolutionary strategy leading to unique genotypes, which can spawn influenza A viruses with pandemic potential. However, the mechanism preventing intertypic reassortment or

  10. The global antigenic diversity of swine influenza A viruses

    DEFF Research Database (Denmark)

    Lewis, Nicola S; Russell, Colin A; Langat, Pinky

    2016-01-01

    Swine influenza presents a substantial disease burden for pig populations worldwide and poses a potential pandemic threat to humans. There is considerable diversity in both H1 and H3 influenza viruses circulating in swine due to the frequent introductions of viruses from humans and birds coupled...... with geographic segregation of global swine populations. Much of this diversity is characterized genetically but the antigenic diversity of these viruses is poorly understood. Critically, the antigenic diversity shapes the risk profile of swine influenza viruses in terms of their epizootic and pandemic potential...

  11. Bovine immunodeficiency-like virus: inactivation in milk by pasteurisation.

    Science.gov (United States)

    Venables, C; Lysons, R; Horigan, M; Stagg, D; Dawson, M

    1997-03-15

    Bioassay was used to determine whether bovine immunodeficiency-like virus (BIV) in milk was inactivated by pasteurisation. Three groups of three calves were inoculated with virus (BIV isolate FL112), milk seeded with virus and milk seeded with virus that had been pasteurised before inoculation, respectively. Seroconversion to BIV was monitored for 12 months by an indirect immunofluorescence assay. The presence of BIV proviral DNA in peripheral blood was determined by a nested polymerase chain reaction (PCR). The animals were euthanized and virus isolation and PCR were attempted on peripheral blood mononunclear cells, prescapular lymph node and spleen. Transmission of BIV was confirmed in the groups that were inoculated with the virus and with the virus in milk, but no evidence of its transmission was demonstrated in the group that received the pasteurised inoculum.

  12. Vaccination against H9N2 avian influenza virus reduces bronchus-associated lymphoid tissue formation in cynomolgus macaques after intranasal virus challenge infection.

    Science.gov (United States)

    Nakayama, Misako; Ozaki, Hiroichi; Itoh, Yasushi; Soda, Kosuke; Ishigaki, Hirohito; Okamatsu, Masatoshi; Sakoda, Yoshihiro; Park, Chun-Ho; Tsuchiya, Hideaki; Kida, Hiroshi; Ogasawara, Kazumasa

    2016-12-01

    H9N2 avian influenza virus causes sporadic human infection. Since humans do not possess acquired immunity specific to this virus, we examined the pathogenicity of an H9N2 virus isolated from a human and then analyzed protective effects of a vaccine in cynomolgus macaques. After intranasal challenge with A/Hong Kong/1073/1999 (H9N2) (HK1073) isolated from a human patient, viruses were isolated from nasal and tracheal swabs in unvaccinated macaques with mild fever and body weight loss. A formalin-inactivated H9N2 whole particle vaccine derived from our virus library was subcutaneously inoculated to macaques. Vaccination induced viral antigen-specific IgG and neutralization activity in sera. After intranasal challenge with H9N2, the virus was detected only the day after inoculation in the vaccinated macaques. Without vaccination, many bronchus-associated lymphoid tissues (BALTs) were formed in the lungs after infection, whereas the numbers of BALTs were smaller and the cytokine responses were weaker in the vaccinated macaques than those in the unvaccinated macaques. These findings indicate that the H9N2 avian influenza virus HK1073 is pathogenic in primates but seems to cause milder symptoms than does H7N9 influenza virus as found in our previous studies and that a formalin-inactivated H9N2 whole particle vaccine induces protective immunity against H9N2 virus. © 2016 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

  13. IgA and neutralizing antibodies to influenza a virus in human milk: a randomized trial of antenatal influenza immunization.

    Science.gov (United States)

    Schlaudecker, Elizabeth P; Steinhoff, Mark C; Omer, Saad B; McNeal, Monica M; Roy, Eliza; Arifeen, Shams E; Dodd, Caitlin N; Raqib, Rubhana; Breiman, Robert F; Zaman, K

    2013-01-01

    Antenatal immunization of mothers with influenza vaccine increases serum antibodies and reduces the rates of influenza illness in mothers and their infants. We report the effect of antenatal immunization on the levels of specific anti-influenza IgA levels in human breast milk. (ClinicalTrials.gov identifier NCT00142389; http://clinicaltrials.gov/ct2/show/NCT00142389). The Mother's Gift study was a prospective, blinded, randomized controlled trial that assigned 340 pregnant Bangladeshi mothers to receive either trivalent inactivated influenza vaccine, or 23-valent pneumococcal polysaccharide vaccine during the third trimester. We evaluated breast milk at birth, 6 weeks, 6 months, and 12 months, and serum at 10 weeks and 12 months. Milk and serum specimens from 57 subjects were assayed for specific IgA antibody to influenza A/New Caledonia (H1N1) using an enzyme-linked immunosorbent assay (ELISA) and a virus neutralization assay, and for total IgA using ELISA. Influenza-specific IgA levels in breast milk were significantly higher in influenza vaccinees than in pneumococcal controls for at least 6 months postpartum (p = 0.04). Geometric mean concentrations ranged from 8.0 to 91.1 ELISA units/ml in vaccinees, versus 2.3 to 13.7 ELISA units/mL in controls. Virus neutralization titers in milk were 1.2 to 3 fold greater in vaccinees, and correlated with influenza-specific IgA levels (r = 0.86). Greater exclusivity of breastfeeding in the first 6 months of life significantly decreased the expected number of respiratory illness with fever episodes in infants of influenza-vaccinated mothers (p = 0.0042) but not in infants of pneumococcal-vaccinated mothers (p = 0.4154). The sustained high levels of actively produced anti-influenza IgA in breast milk and the decreased infant episodes of respiratory illness with fever suggest that breastfeeding may provide local mucosal protection for the infant for at least 6 months. Studies are needed to determine the

  14. Influenza AH1N2 Viruses, United Kingdom, 2001?02 Influenza Season

    OpenAIRE

    Ellis, Joanna S.; Alvarez-Aguero, Adriana; Gregory, Vicky; Lin, Yi Pu; Hay, A.; Zambon, Maria C.

    2003-01-01

    During the winter of 2001?02, influenza AH1N2 viruses were detected for the first time in humans in the U.K. The H1N2 viruses co-circulated with H3N2 viruses and a very small number of H1N1 viruses and were isolated in the community and hospitalized patients, predominantly from children

  15. Influenza virus and endothelial cells: a species specific relationship

    Directory of Open Access Journals (Sweden)

    Kirsty Renfree Short

    2014-12-01

    Full Text Available Influenza A virus infection is an important cause of respiratory disease in humans. The original reservoirs of influenza A virus are wild waterfowl and shorebirds, where virus infection causes limited, if any, disease. Both in humans and in wild waterbirds, epithelial cells are the main target of infection. However, influenza virus can spread from wild bird species to terrestrial poultry. Here, the virus can evolve into highly pathogenic avian influenza (HPAI. Part of this evolution involves increased viral tropism for endothelial cells. HPAI virus infections not only cause severe disease in chickens and other terrestrial poultry species but can also spread to humans and back to wild bird populations. Here, we review the role of the endothelium in the pathogenesis of influenza virus infection in wild birds, terrestrial poultry and humans with a particular focus on HPAI viruses. We demonstrate that whilst the endothelium is an important target of virus infection in terrestrial poultry and some wild bird species, in humans the endothelium is more important in controlling the local inflammatory milieu. Thus, the endothelium plays an important, but species-specific, role in the pathogenesis of influenza virus infection.

  16. Avian influenza in shorebirds: experimental infection of ruddy turnstones (Arenaria interpres) with avian influenza virus

    Science.gov (United States)

    Hall, Jeffrey S.; Krauss, Scott; Franson, J. Christian; TeSlaa, Joshua L.; Nashold, Sean W.; Stallknecht, David E.; Webby, Richard J.; Webster, Robert G.

    2013-01-01

    Background: Low pathogenic avian influenza viruses (LPAIV) have been reported in shorebirds, especially at Delaware Bay, USA, during spring migration. However, data on patterns of virus excretion, minimal infectious doses, and clinical outcome are lacking. The ruddy turnstone (Arenaria interpres) is the shorebird species with the highest prevalence of influenza virus at Delaware Bay. Objectives: The primary objective of this study was to experimentally assess the patterns of influenza virus excretion, minimal infectious doses, and clinical outcome in ruddy turnstones. Methods: We experimentally challenged ruddy turnstones using a common LPAIV shorebird isolate, an LPAIV waterfowl isolate, or a highly pathogenic H5N1 avian influenza virus. Cloacal and oral swabs and sera were analyzed from each bird. Results: Most ruddy turnstones had pre-existing antibodies to avian influenza virus, and many were infected at the time of capture. The infectious doses for each challenge virus were similar (103·6–104·16 EID50), regardless of exposure history. All infected birds excreted similar amounts of virus and showed no clinical signs of disease or mortality. Influenza A-specific antibodies remained detectable for at least 2 months after inoculation. Conclusions: These results provide a reference for interpretation of surveillance data, modeling, and predicting the risks of avian influenza transmission and movement in these important hosts.

  17. Within-Host Evolution of Human Influenza Virus.

    Science.gov (United States)

    Xue, Katherine S; Moncla, Louise H; Bedford, Trevor; Bloom, Jesse D

    2018-03-10

    The rapid global evolution of influenza virus begins with mutations that arise de novo in individual infections, but little is known about how evolution occurs within hosts. We review recent progress in understanding how and why influenza viruses evolve within human hosts. Advances in deep sequencing make it possible to measure within-host genetic diversity in both acute and chronic influenza infections. Factors like antigenic selection, antiviral treatment, tissue specificity, spatial structure, and multiplicity of infection may affect how influenza viruses evolve within human hosts. Studies of within-host evolution can contribute to our understanding of the evolutionary and epidemiological factors that shape influenza virus's global evolution. Copyright © 2018 Elsevier Ltd. All rights reserved.

  18. Molecular diagnostics of Avian influenza virus

    Directory of Open Access Journals (Sweden)

    Petrović Tamaš

    2006-01-01

    Full Text Available The success of supervizing an infectious disease depends on the ability for speedy detection and characterization of the cause and the forming of a corresponding system for examining the success of control implemented in order to prevent a recurrence of the disease. Since influenza viruses continue to circle, causing significant morbidity and mortality both among the human population and among animals all over the world, it is essential to secure the timely identification and monitoring of the strains that are in circulation. The speedy detection and characterization of new highly-virulent varieties is one of the priorities of the World Health Organization monitoring network. The implementation of molecular methods has an increasingly significant role in diagnostics and the monitoring of the influenza virus. Among a large number of molecular methods, the one particularly in use is the reverse transcription-polimerase chain reaction (PT-PCR. Technological progress in the area of the conducting of molecular methods has enabled that we can prove, in one day, using the RT-PCR method even very small quantities of the infective agent in a sample. In an obtained PCR product, we can relatively easily establish the nucleotide sequence, a detailed analysis and molecular epidemiology of the circulating strains. The molecular diagnostics procedure (RT-PCR is based on the correct choice or designing of primers depending on the desired knowledge. In order to obtain a specific diagnosis of influenza A, B or C, primers are used which multiply internal genes, such as the nucleoprotein (NP or matrix gene (M, because these are genes that are highly conserved among the virus types. In the event that we are interested in the subtype of influenza A, after obtaining a positive reaction, primers for genes of surface antigens are selected, such as hemagglutinin. Following the correct detection of the H subtype, it is possible to establish the virus virulence through the

  19. A New Adjuvant Combined with Inactivated Influenza Enhances Specific CD8 T Cell Response in Mice and Decreases Symptoms in Swine Upon Challenge.

    Science.gov (United States)

    Bouguyon, Edwige; Goncalves, Elodie; Shevtsov, Alexander; Maisonnasse, Pauline; Remyga, Stepan; Goryushev, Oleg; Deville, Sebastien; Bertho, Nicolas; Ben Arous, Juliette

    2015-11-01

    Vaccination is the most effective way to control swine influenza virus (SIV) in the field. Classical vaccines are based on inactivated antigens formulated with an oil emulsion or a polymeric adjuvant. Standard adjuvants enhance the humoral response and orient the immune response toward a Th2 response. An important issue is that current vaccines do not protect against new strains. One approach to improve cross-protection is to enhance Th1 and cytotoxic responses. The development of adjuvants orienting the immune response of inactivated vaccines toward Th1/Cytotoxic responses would be highly beneficial. This study shows that the water in oil in water emulsion adjuvant Montanide™ ISA 201 VG allows the induction of anti-influenza CD8 T cell in mice and induces homologous protection against an H1N1 challenge in swine. Such adjuvants that induce both humoral and cell-mediated immunity could improve the protection conferred by SIV vaccines in the field.

  20. Evolution of Therapeutic Antibodies, Influenza Virus Biology, Influenza, and Influenza Immunotherapy

    Directory of Open Access Journals (Sweden)

    Urai Chaisri

    2018-01-01

    Full Text Available This narrative review article summarizes past and current technologies for generating antibodies for passive immunization/immunotherapy. Contemporary DNA and protein technologies have facilitated the development of engineered therapeutic monoclonal antibodies in a variety of formats according to the required effector functions. Chimeric, humanized, and human monoclonal antibodies to antigenic/epitopic myriads with less immunogenicity than animal-derived antibodies in human recipients can be produced in vitro. Immunotherapy with ready-to-use antibodies has gained wide acceptance as a powerful treatment against both infectious and noninfectious diseases. Influenza, a highly contagious disease, precipitates annual epidemics and occasional pandemics, resulting in high health and economic burden worldwide. Currently available drugs are becoming less and less effective against this rapidly mutating virus. Alternative treatment strategies are needed, particularly for individuals at high risk for severe morbidity. In a setting where vaccines are not yet protective or available, human antibodies that are broadly effective against various influenza subtypes could be highly efficacious in lowering morbidity and mortality and controlling unprecedented epidemic/pandemic. Prototypes of human single-chain antibodies to several conserved proteins of influenza virus with no Fc portion (hence, no ADE effect in recipients are available. These antibodies have high potential as a novel, safe, and effective anti-influenza agent.

  1. Influenza vaccines: from whole virus preparations to recombinant protein technology.

    Science.gov (United States)

    Huber, Victor C

    2014-01-01

    Vaccination against influenza represents our most effective form of prevention. Historical approaches toward vaccine creation and production have yielded highly effective vaccines that are safe and immunogenic. Despite their effectiveness, these historical approaches do not allow for the incorporation of changes into the vaccine in a timely manner. In 2013, a recombinant protein-based vaccine that induces immunity toward the influenza virus hemagglutinin was approved for use in the USA. This vaccine represents the first approved vaccine formulation that does not require an influenza virus intermediate for production. This review presents a brief history of influenza vaccines, with insight into the potential future application of vaccines generated using recombinant technology.

  2. The 2009 A (H1N1) influenza virus pandemic: A review.

    Science.gov (United States)

    Girard, Marc P; Tam, John S; Assossou, Olga M; Kieny, Marie Paule

    2010-07-12

    In March and early April 2009 a new swine-origin influenza virus (S-OIV), A (H1N1), emerged in Mexico and the USA. The virus quickly spread worldwide through human-to-human transmission. In view of the number of countries and communities which were reporting human cases, the World Health Organization raised the influenza pandemic alert to the highest level (level 6) on June 11, 2009. The propensity of the virus to primarily affect children, young adults and pregnant women, especially those with an underlying lung or cardiac disease condition, and the substantial increase in rate of hospitalizations, prompted the efforts of the pharmaceutical industry, including new manufacturers from China, Thailand, India and South America, to develop pandemic H1N1 influenza vaccines. All currently registered vaccines were tested for safety and immunogenicity in clinical trials on human volunteers. All were found to be safe and to elicit potentially protective antibody responses after the administration of a single dose of vaccine, including split inactivated vaccines with or without adjuvant, whole-virion vaccines and live-attenuated vaccines. The need for an increased surveillance of influenza virus circulation in swine is outlined. Copyright 2010. Published by Elsevier Ltd.

  3. Influenza virus sequence feature variant type analysis: evidence of a role for NS1 in influenza virus host range restriction.

    Science.gov (United States)

    Noronha, Jyothi M; Liu, Mengya; Squires, R Burke; Pickett, Brett E; Hale, Benjamin G; Air, Gillian M; Galloway, Summer E; Takimoto, Toru; Schmolke, Mirco; Hunt, Victoria; Klem, Edward; García-Sastre, Adolfo; McGee, Monnie; Scheuermann, Richard H

    2012-05-01

    Genetic drift of influenza virus genomic sequences occurs through the combined effects of sequence alterations introduced by a low-fidelity polymerase and the varying selective pressures experienced as the virus migrates through different host environments. While traditional phylogenetic analysis is useful in tracking the evolutionary heritage of these viruses, the specific genetic determinants that dictate important phenotypic characteristics are often difficult to discern within the complex genetic background arising through evolution. Here we describe a novel influenza virus sequence feature variant type (Flu-SFVT) approach, made available through the public Influenza Research Database resource (www.fludb.org), in which variant types (VTs) identified in defined influenza virus protein sequence features (SFs) are used for genotype-phenotype association studies. Since SFs have been defined for all influenza virus proteins based on known structural, functional, and immune epitope recognition properties, the Flu-SFVT approach allows the rapid identification of the molecular genetic determinants of important influenza virus characteristics and their connection to underlying biological functions. We demonstrate the use of the SFVT approach to obtain statistical evidence for effects of NS1 protein sequence variations in dictating influenza virus host range restriction.

  4. Vaccination with Recombinant Parainfluenza Virus 5 Expressing Neuraminidase Protects against Homologous and Heterologous Influenza Virus Challenge.

    Science.gov (United States)

    Mooney, Alaina J; Gabbard, Jon D; Li, Zhuo; Dlugolenski, Daniel A; Johnson, Scott K; Tripp, Ralph A; He, Biao; Tompkins, S Mark

    2017-12-01

    Seasonal human influenza virus continues to cause morbidity and mortality annually, and highly pathogenic avian influenza (HPAI) viruses along with other emerging influenza viruses continue to pose pandemic threats. Vaccination is considered the most effective measure for controlling influenza; however, current strategies rely on a precise vaccine match with currently circulating virus strains for efficacy, requiring constant surveillance and regular development of matched vaccines. Current vaccines focus on eliciting specific antibody responses against the hemagglutinin (HA) surface glycoprotein; however, the diversity of HAs across species and antigenic drift of circulating strains enable the evasion of virus-inhibiting antibody responses, resulting in vaccine failure. The neuraminidase (NA) surface glycoprotein, while diverse, has a conserved enzymatic site and presents an appealing target for priming broadly effective antibody responses. Here we show that vaccination with parainfluenza virus 5 (PIV5), a promising live viral vector expressing NA from avian (H5N1) or pandemic (H1N1) influenza virus, elicited NA-specific antibody and T cell responses, which conferred protection against homologous and heterologous influenza virus challenges. Vaccination with PIV5-N1 NA provided cross-protection against challenge with a heterosubtypic (H3N2) virus. Experiments using antibody transfer indicate that antibodies to NA have an important role in protection. These findings indicate that PIV5 expressing NA may be effective as a broadly protective vaccine against seasonal influenza and emerging pandemic threats. IMPORTANCE Seasonal influenza viruses cause considerable morbidity and mortality annually, while emerging viruses pose potential pandemic threats. Currently licensed influenza virus vaccines rely on the antigenic match of hemagglutinin (HA) for vaccine strain selection, and most vaccines rely on HA inhibition titers to determine efficacy, despite the growing

  5. Efficacy of a pandemic (H1N1) 2009 virus vaccine in pigs against the pandemic influenza virus is superior to commercially available swine influenza vaccines.

    Science.gov (United States)

    Loeffen, W L A; Stockhofe, N; Weesendorp, E; van Zoelen-Bos, D; Heutink, R; Quak, S; Goovaerts, D; Heldens, J G M; Maas, R; Moormann, R J; Koch, G

    2011-09-28

    In April 2009 a new influenza A/H1N1 strain, currently named "pandemic (H1N1) influenza 2009" (H1N1v), started the first official pandemic in humans since 1968. Several incursions of this virus in pig herds have also been reported from all over the world. Vaccination of pigs may be an option to reduce exposure of human contacts with infected pigs, thereby preventing cross-species transfer, but also to protect pigs themselves, should this virus cause damage in the pig population. Three swine influenza vaccines, two of them commercially available and one experimental, were therefore tested and compared for their efficacy against an H1N1v challenge. One of the commercial vaccines is based on an American classical H1N1 influenza strain, the other is based on a European avian H1N1 influenza strain. The experimental vaccine is based on reassortant virus NYMC X179A (containing the hemagglutinin (HA) and neuraminidase (NA) genes of A/California/7/2009 (H1N1v) and the internal genes of A/Puerto Rico/8/34 (H1N1)). Excretion of infectious virus was reduced by 0.5-3 log(10) by the commercial vaccines, depending on vaccine and sample type. Both vaccines were able to reduce virus replication especially in the lower respiratory tract, with less pathological lesions in vaccinated and subsequently challenged pigs than in unvaccinated controls. In pigs vaccinated with the experimental vaccine, excretion levels of infectious virus in nasal and oropharyngeal swabs, were at or below 1 log(10)TCID(50) per swab and lasted for only 1 or 2 days. An inactivated vaccine containing the HA and NA of an H1N1v is able to protect pigs from an infection with H1N1v, whereas swine influenza vaccines that are currently available are of limited efficaciousness. Whether vaccination of pigs against H1N1v will become opportune remains to be seen and will depend on future evolution of this strain in the pig population. Close monitoring of the pig population, focussing on presence and evolution of

  6. A competitive-inhibiton radioimmunoassay for influenza virus envelope antigens

    International Nuclear Information System (INIS)

    Russ, G.; Styk, B.; Vareckova, E.; Polakova, K.

    1976-01-01

    A double-antibody competitive-inhibition radioimmunoassay for influenza virus envelope antigens is described. A viral antigen preparation from influenza A virus recombinant MRC11 [antigenically identical to A/Port Chalmers/1/73 (H3N2)] consisting of haemagglutinin and neuraminidase was labelled with radioiodine. Rabbit antisera were allowed to react with the labelled antigen and the resultant antigen-antibody complexes were precipitated with the appropriate antiglobulin. The competitive-inhibition radioimmunoassay very sensitively elucidated differences even among closely related influenza virus strains. Attempts have been made to eliminate neuraminidase from radioimmunoprecipitation to obtain a competitive-inhibition radioimmunoassay system for haemagglutinin alone. (author)

  7. Ultraviolet inactivation of avian sarcoma virus: biological and biochemical analysis

    International Nuclear Information System (INIS)

    Owada, M.; Ihara, S.; Toyoshima, K.; Kozai, Y.; Sugino, Y.

    1976-01-01

    The rate of inactivation by ultraviolet light of the focus-forming capacity of avian sarcoma virus was almost the same as that of the virus-producing capacity, measured as plaque formation. In addition, no significant difference was observed in inactivation of the transforming capacity assayed on C/BE chick embryo fibroblasts (CEF), which carry endogenous avian tumor virus DNA, and on duck embryo fibroblasts (DEF), which are known to be devoid of this DNA. All foci induced by nonirradiated virus produced infectious sarcoma virus, but some of the foci induced by uv-irradiated virus did not produce infectious virus of either transforming or transformation-defective type. The proportion of nonproducer foci was 3.4 times more in DEF than in gs - chf - CEF. RNAs extracted from uv-irradiated virions by sodium dodecyl sulfate (SDS) treatment were found to be composed of 60--70 S and 4 S RNAs by analysis in a sucrose gradient containing 0.5 percent SDS. The large RNA, however, became hydrophobic after irradiation and was sedimented with SDS by addition of one drop of saturated potassium chloride solution. This RNA was not dissociated into 30--40S components by heating at 100 0 for 45 sec, unlike 60--70 S RNA from uv-irradiated virions. After SDS--Pronase treatment, the 60--70 S RNA from uv-irradiated virions no longer had these altered characteristics. Reverse transcriptase activity with the endogenous template decreased in parallel with increase in the uv dose. The reduction rate was similar to that assayed with exogenous template or in the presence of actinomycin D. These data strongly suggest that RNA damage is not the only cause of virus inactivation by uv light

  8. Some biological consequences of disintegration of 3H and 14C incorporated in an influenza virus

    International Nuclear Information System (INIS)

    Prokudina, E.N.; Semenova, N.P.; Yamnikova, S.S.; Zhdanov, V.M.

    1987-01-01

    An influenza virus labeled with 3 H-uridine losses its infectiousness when stored for a long time. It is suggested that disintegration of tritium incorporated into virus RNA causes lethal intramolecular modifications therein. At the same time, the antigenic activity of virus nucleoprotein decreases perhaps due to the direct effect of tritium. The comparison of the degree of inactivation of various antigenic sites of the nucleoprotein within a virus, labeled with 3 H-uridine, suggests that they are located at different distances from RNA. A long-term action of 3 H disintegration on RNA of a maturing virus decreased the yield probably due to the injury of the intracellular virus RNA during the infections process. Upon storage of the influenza virus labelle with 14 C-amino acids the antigenic properties are reduced by the nucleoprotein while the infectiousness remains unaffected. The long-term effect of 14 C disintegration on proteins of the maturing virus does not lead to fatal outcome

  9. Effective lethal mutagenesis of influenza virus by three nucleoside analogs.

    Science.gov (United States)

    Pauly, Matthew D; Lauring, Adam S

    2015-04-01

    Lethal mutagenesis is a broad-spectrum antiviral strategy that exploits the high mutation rate and low mutational tolerance of many RNA viruses. This approach uses mutagenic drugs to increase viral mutation rates and burden viral populations with mutations that reduce the number of infectious progeny. We investigated the effectiveness of lethal mutagenesis as a strategy against influenza virus using three nucleoside analogs, ribavirin, 5-azacytidine, and 5-fluorouracil. All three drugs were active against a panel of seasonal H3N2 and laboratory-adapted H1N1 strains. We found that each drug increased the frequency of mutations in influenza virus populations and decreased the virus' specific infectivity, indicating a mutagenic mode of action. We were able to drive viral populations to extinction by passaging influenza virus in the presence of each drug, indicating that complete lethal mutagenesis of influenza virus populations can be achieved when a sufficient mutational burden is applied. Population-wide resistance to these mutagenic agents did not arise after serial passage of influenza virus populations in sublethal concentrations of drug. Sequencing of these drug-passaged viral populations revealed genome-wide accumulation of mutations at low frequency. The replicative capacity of drug-passaged populations was reduced at higher multiplicities of infection, suggesting the presence of defective interfering particles and a possible barrier to the evolution of resistance. Together, our data suggest that lethal mutagenesis may be a particularly effective therapeutic approach with a high genetic barrier to resistance for influenza virus. Influenza virus is an RNA virus that causes significant morbidity and mortality during annual epidemics. Novel therapies for RNA viruses are needed due to the ease with which these viruses evolve resistance to existing therapeutics. Lethal mutagenesis is a broad-spectrum strategy that exploits the high mutation rate and the low

  10. Reverse Genetics Approaches for the Development of Influenza Vaccines

    Science.gov (United States)

    Nogales, Aitor; Martínez-Sobrido, Luis

    2016-01-01

    Influenza viruses cause annual seasonal epidemics and occasional pandemics of human respiratory disease. Influenza virus infections represent a serious public health and economic problem, which are most effectively prevented through vaccination. However, influenza viruses undergo continual antigenic variation, which requires either the annual reformulation of seasonal influenza vaccines or the rapid generation of vaccines against potential pandemic virus strains. The segmented nature of influenza virus allows for the reassortment between two or more viruses within a co-infected cell, and this characteristic has also been harnessed in the laboratory to generate reassortant viruses for their use as either inactivated or live-attenuated influenza vaccines. With the implementation of plasmid-based reverse genetics techniques, it is now possible to engineer recombinant influenza viruses entirely from full-length complementary DNA copies of the viral genome by transfection of susceptible cells. These reverse genetics systems have provided investigators with novel and powerful approaches to answer important questions about the biology of influenza viruses, including the function of viral proteins, their interaction with cellular host factors and the mechanisms of influenza virus transmission and pathogenesis. In addition, reverse genetics techniques have allowed the generation of recombinant influenza viruses, providing a powerful technology to develop both inactivated and live-attenuated influenza vaccines. In this review, we will summarize the current knowledge of state-of-the-art, plasmid-based, influenza reverse genetics approaches and their implementation to provide rapid, convenient, safe and more effective influenza inactivated or live-attenuated vaccines. PMID:28025504

  11. Production of inactivated influenza H5N1 vaccines from MDCK cells in serum-free medium.

    Directory of Open Access Journals (Sweden)

    Alan Yung-Chih Hu

    Full Text Available BACKGROUND: Highly pathogenic influenza viruses pose a constant threat which could lead to a global pandemic. Vaccination remains the principal measure to reduce morbidity and mortality from such pandemics. The availability and surging demand for pandemic vaccines needs to be addressed in the preparedness plans. This study presents an improved high-yield manufacturing process for the inactivated influenza H5N1 vaccines using Madin-Darby canine kidney (MDCK cells grown in a serum-free (SF medium microcarrier cell culture system. PRINCIPAL FINDING: The current study has evaluated the performance of cell adaptation switched from serum-containing (SC medium to several commercial SF media. The selected SF medium was further evaluated in various bioreactor culture systems for process scale-up evaluation. No significant difference was found in the cell growth in different sizes of bioreactors studied. In the 7.5 L bioreactor runs, the cell concentration reached to 2.3 × 10(6 cells/mL after 5 days. The maximum virus titers of 1024 Hemagglutinin (HA units/50 µL and 7.1 ± 0.3 × 10(8 pfu/mL were obtained after 3 days infection. The concentration of HA antigen as determined by SRID was found to be 14.1 µg/mL which was higher than those obtained from the SC medium. A mouse immunogenicity study showed that the formalin-inactivated purified SF vaccine candidate formulated with alum adjuvant could induce protective level of virus neutralization titers similar to those obtained from the SC medium. In addition, the H5N1 viruses produced from either SC or SF media showed the same antigenic reactivity with the NIBRG14 standard antisera. CONCLUSIONS: The advantages of this SF cell-based manufacturing process could reduce the animal serum contamination, the cost and lot-to-lot variation of SC medium production. This study provides useful information to manufacturers that are planning to use SF medium for cell-based influenza vaccine production.

  12. Immunogenicity and Safety of the New Inactivated Quadrivalent Influenza Vaccine Vaxigrip Tetra: Preliminary Results in Children ≥6 Months and Older Adults

    Directory of Open Access Journals (Sweden)

    Emanuele Montomoli

    2018-03-01

    Full Text Available Since the mid-1980s, two lineages of influenza B viruses have been distinguished. These can co-circulate, limiting the protection provided by inactivated trivalent influenza vaccines (TIVs. This has prompted efforts to formulate quadrivalent influenza vaccines (QIVs, to enhance protection against circulating influenza B viruses. This review describes the results obtained from seven phase III clinical trials evaluating the immunogenicity, safety, and lot-to-lot consistency of a new quadrivalent split-virion influenza vaccine (Vaxigrip Tetra® formulated by adding a second B strain to the already licensed TIV. Since Vaxigrip Tetra was developed by means of a manufacturing process strictly related to that used for TIV, the data on the safety profile of TIV are considered supportive of that of Vaxigrip Tetra. The safety and immunogenicity of Vaxigrip Tetra were similar to those of the corresponding licensed TIV. Moreover, the new vaccine elicits a superior immune response towards the additional strain, without affecting immunogenicity towards the other three strains. Vaxigrip Tetra is well tolerated, has aroused no safety concerns, and is recommended for the active immunization of individuals aged ≥6 months. In addition, preliminary data confirm its immunogenicity and safety even in children aged 6–35 months and its immunogenicity in older subjects (aged 66–80 years.

  13. Enteric virus removal inactivation by coal-based media

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, A.; Chaudhuri, M. [Indian Institute of Technology, Kanpur (India). Dept. of Civil Engineering

    1995-02-01

    Four coal-based media, viz. alum-pretreated or ferric hydroxide-impregnated Giridih bituminous coal and lignite (alum-GBC, Fe-GBC; alum-lignite and Fe-Lignite) were laboratory tested to assess their potential in removing/inactivating enteric viruses in water. Batch-sorption screening tests, employing a poliovirus-spiked canal water, indicated high poliovirus sorption by Fe-GBC and alum-GBC in a short contact time of 5 min. Based on the results of further batch-sorption tests, using silver incorporated media (alum/Ag-GBC, alum-GBC-Ag and Fe-GBC-Ag), as well as aesthetic water quality consideration and previous findings on removal of coliforms and turbidity, alum/Ag-GBC, alum-GBC and alum-GBC-AG were included in downflow column studies employing poliovirus-spiked canal water. All three media showed potential in removing/inactivating enteric viruses. In a separate column study employing a joint challenge of poliovirus and rotavirus, alum/Ag-GBC removed 59.3-86.5% of the viruses along with more than 99% reduction in indigenous heterotrophic bacteria. Alum/silver-pretreated bituminous coal medium appears promising for use in household water filters in rural areas of the developing world. However, improved medium preparation to further enhance its efficiency is needed; also, its efficacy in removing/inactivating indigenous enteric bacteria, viruses and protozoa has to be ensured and practicalities or economics of application need to be considered.

  14. Continental synchronicity of human influenza virus epidemics despite climactic variation.

    Science.gov (United States)

    Geoghegan, Jemma L; Saavedra, Aldo F; Duchêne, Sebastián; Sullivan, Sheena; Barr, Ian; Holmes, Edward C

    2018-01-01

    The factors that determine the pattern and rate of spread of influenza virus at a continental-scale are uncertain. Although recent work suggests that influenza epidemics in the United States exhibit a strong geographical correlation, the spatiotemporal dynamics of influenza in Australia, a country and continent of approximately similar size and climate complexity but with a far smaller population, are not known. Using a unique combination of large-scale laboratory-confirmed influenza surveillance comprising >450,000 entries and genomic sequence data we determined the local-level spatial diffusion of this important human pathogen nationwide in Australia. We used laboratory-confirmed influenza data to characterize the spread of influenza virus across Australia during 2007-2016. The onset of established epidemics varied across seasons, with highly synchronized epidemics coinciding with the emergence of antigenically distinct viruses, particularly during the 2009 A/H1N1 pandemic. The onset of epidemics was largely synchronized between the most populous cities, even those separated by distances of >3000 km and those that experience vastly diverse climates. In addition, by analyzing global phylogeographic patterns we show that the synchronized dissemination of influenza across Australian cities involved multiple introductions from the global influenza population, coupled with strong domestic connectivity, rather than through the distinct radial patterns of geographic dispersal that are driven by work-flow transmission as observed in the United States. In addition, by comparing the spatial structure of influenza A and B, we found that these viruses tended to occupy different geographic regions, and peak in different seasons, perhaps indicative of moderate cross-protective immunity or viral interference effects. The highly synchronized outbreaks of influenza virus at a continental-scale revealed here highlight the importance of coordinated public health responses in the

  15. Immunopotentiators Improve the Efficacy of Oil-Emulsion-Inactivated Avian Influenza Vaccine in Chickens, Ducks and Geese.

    Directory of Open Access Journals (Sweden)

    Jihu Lu

    Full Text Available Combination of CVCVA5 adjuvant and commercial avian influenza (AI vaccine has been previously demonstrated to provide good protection against different AI viruses in chickens. In this study, we further investigated the protective immunity of CVCVA5-adjuvanted oil-emulsion inactivated AI vaccine in chickens, ducks and geese. Compared to the commercial H5 inactivated vaccine, the H5-CVCVA5 vaccine induced significantly higher titers of hemaglutinin inhibitory antibodies in three lines of broiler chickens and ducks, elongated the antibody persistence periods in geese, elevated the levels of cross serum neutralization antibody against different clade and subclade H5 AI viruses in chicken embryos. High levels of mucosal antibody were detected in chickens injected with the H5 or H9-CVCA5 vaccine. Furthermore, cellular immune response was markedly improved in terms of increasing the serum levels of cytokine interferon-γ and interleukine 4, promoting proliferation of splenocytes and upregulating cytotoxicity activity in both H5- and H9-CVCVA5 vaccinated chickens. Together, these results provide evidence that AI vaccines supplemented with CVCVA5 adjuvant is a promising approach for overcoming the limitation of vaccine strain specificity of protection.

  16. Population dynamics of swine influenza virus in finishing pigs

    NARCIS (Netherlands)

    Loeffen, W.L.A.

    2008-01-01

    Influenza virus infections in swine were first noticed in the US in 1918, during the human pandemic of the Spanish flu. In Europe, seroprevalences for the three most common swine influenza strains at the moment, H1N1, H3N2 and H1N2, range from 20-80% in finishing pigs at the end of the finishing

  17. Pathogenicity of highly pathogenic avian influenza virus in mammals

    NARCIS (Netherlands)

    de Wit, Emmie; Kawaoka, Yoshihiro; de Jong, Menno D.; Fouchier, Ron A. M.

    2008-01-01

    In recent years, there has been an increase in outbreaks of highly pathogenic avian influenza (HPAI) in poultry. Occasionally, these outbreaks have resulted in transmission of influenza viruses to humans and other mammals, with symptoms ranging from conjunctivitis to pneumonia and death. Here, the

  18. Virus inactivation studies using ion beams, electron and gamma irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Smolko, Eduardo E. [Laboratorio de Polimeros, Grupo Aplicaciones Industriales, Unidad de Aplicaciones Tecnologicas y Agropecuarias, Centro Atomico Ezeiza, Comision Nacional de Energia Atomica, Pbro. Juan Gonzalez y Aragon 15, C.P. B1802AYA Ezeiza, Buenos Aires (Argentina)]. E-mail: smolko@cae.cnea.gov.ar; Lombardo, Jorge H. [Biotech S.A., C.P. 1754 Buenos Aires (Argentina)

    2005-07-01

    Known methods of virus inactivation are based on the chemical action of some substances such as acetylethylenimine, betapropiolactone, glycidalaldehyde, formaldehyde, etc. In such a process, the viral suspension should be kept at room or higher temperatures for 24-48 h. Under these conditions, physical and chemical agents act to degrade the virus antigenic proteins. On the contrary with ionizing radiations at low temperatures, the treatment does not cause such degradation allowing the study of different viral functions. In this work, particle ({alpha}, d and ss) and {gamma} irradiations were used for partial and total inactivation of Foot and Mouth Disease Virus (FMDV), Rauscher Leukemia Virus (RLV) and Herpes Simplex Virus (HSV). Obtention of the D{sub 37} dose from survival curves and the application of the target theory, permitted the determination of molecular weight of the nucleic acid genomes, EBR values and useful information for vaccine preparation. For RLV virus, a two target model of the RNA genome was deduced in accordance with biological information while from data from the literature and our own work on the structure of the scrapie prion, considering the molecular weight obtained by application of the theory, a new model for prion replication is presented, based on a trimer molecule.

  19. Virus inactivation studies using ion beams, electron and gamma irradiation

    International Nuclear Information System (INIS)

    Smolko, Eduardo E.; Lombardo, Jorge H.

    2005-01-01

    Known methods of virus inactivation are based on the chemical action of some substances such as acetylethylenimine, betapropiolactone, glycidalaldehyde, formaldehyde, etc. In such a process, the viral suspension should be kept at room or higher temperatures for 24-48 h. Under these conditions, physical and chemical agents act to degrade the virus antigenic proteins. On the contrary with ionizing radiations at low temperatures, the treatment does not cause such degradation allowing the study of different viral functions. In this work, particle (α, d and ss) and γ irradiations were used for partial and total inactivation of Foot and Mouth Disease Virus (FMDV), Rauscher Leukemia Virus (RLV) and Herpes Simplex Virus (HSV). Obtention of the D 37 dose from survival curves and the application of the target theory, permitted the determination of molecular weight of the nucleic acid genomes, EBR values and useful information for vaccine preparation. For RLV virus, a two target model of the RNA genome was deduced in accordance with biological information while from data from the literature and our own work on the structure of the scrapie prion, considering the molecular weight obtained by application of the theory, a new model for prion replication is presented, based on a trimer molecule

  20. Modes of transmission of influenza B virus in households.

    Directory of Open Access Journals (Sweden)

    Benjamin J Cowling

    Full Text Available While influenza A and B viruses can be transmitted via respiratory droplets, the importance of small droplet nuclei "aerosols" in transmission is controversial.In Hong Kong and Bangkok, in 2008-11, subjects were recruited from outpatient clinics if they had recent onset of acute respiratory illness and none of their household contacts were ill. Following a positive rapid influenza diagnostic test result, subjects were randomly allocated to one of three household-based interventions: hand hygiene, hand hygiene plus face masks, and a control group. Index cases plus their household contacts were followed for 7-10 days to identify secondary infections by reverse transcription polymerase chain reaction (RT-PCR testing of respiratory specimens. Index cases with RT-PCR-confirmed influenza B were included in the present analyses. We used a mathematical model to make inferences on the modes of transmission, facilitated by apparent differences in clinical presentation of secondary infections resulting from aerosol transmission. We estimated that approximately 37% and 26% of influenza B virus transmission was via the aerosol mode in households in Hong Kong and Bangkok, respectively. In the fitted model, influenza B virus infections were associated with a 56%-72% risk of fever plus cough if infected via aerosol route, and a 23%-31% risk of fever plus cough if infected via the other two modes of transmission.Aerosol transmission may be an important mode of spread of influenza B virus. The point estimates of aerosol transmission were slightly lower for influenza B virus compared to previously published estimates for influenza A virus in both Hong Kong and Bangkok. Caution should be taken in interpreting these findings because of the multiple assumptions inherent in the model, including that there is limited biological evidence to date supporting a difference in the clinical features of influenza B virus infection by different modes.

  1. Influenza research database: an integrated bioinformatics resource for influenza virus research

    Science.gov (United States)

    The Influenza Research Database (IRD) is a U.S. National Institute of Allergy and Infectious Diseases (NIAID)-sponsored Bioinformatics Resource Center dedicated to providing bioinformatics support for influenza virus research. IRD facilitates the research and development of vaccines, diagnostics, an...

  2. Comparison of two different methods for inactivation of viruses in serum

    DEFF Research Database (Denmark)

    Preuss, T.; Kamstrup, Søren; Kyvsgaard, N.C.

    1997-01-01

    enterovirus (PEV) was inactivated within 3 h, The inactivation with electron-beam irradiation resulted in almost linear curves in a semilogarithmic plot of virus titer versus irradiation dose, reflecting a first-order inactivation, The rate of inactivation was almost twice as fast in the liquid samples...

  3. Influenza-associated encephalopathy: no evidence for neuroinvasion by influenza virus nor for reactivation of human herpesvirus 6 or 7.

    NARCIS (Netherlands)

    van Zeijl, J.H.; Bakkers, J.; Wilbrink, B.; Melchers, W.J.; Mullaart, R.A.; Galama, J.M.

    2005-01-01

    During 2 consecutive influenza seasons we investigated the presence of influenza virus, human herpesvirus (HHV) type 6, and HHV-7 in cerebrospinal fluid samples from 9 white children suffering from influenza-associated encephalopathy. We conclude that it is unlikely that neuroinvasion by influenza

  4. The effect of various disinfectants on detection of avian influenza virus by real time RT-PCR.

    Science.gov (United States)

    Suarez, D L; Spackman, E; Senne, D A; Bulaga, L; Welsch, A C; Froberg, K

    2003-01-01

    An avian influenza (AI) real time reverse transcriptase-polymerase chain reaction (RRT-PCR) test was previously shown to be a rapid and sensitive method to identify AI virus-infected birds in live-bird markets (LBMs). The test can also be used to identify avian influenza virus (AIV) from environmental samples. Consequently, the use of RRT-PCR was being considered as a component of the influenza eradication program in the LBMs to assure that each market was properly cleaned and disinfected before allowing the markets to be restocked. However, the RRT-PCR test cannot differentiate between live and inactivated virus, particularly in environmental samples where the RRT-PCR test potentially could amplify virus that had been inactivated by commonly used disinfectants, resulting in a false positive test result. To determine whether this is a valid concern, a study was conducted in three New Jersey LBMs that were previously shown to be positive for the H7N2 AIV. Environmental samples were collected from all three markets following thorough cleaning and disinfection with a phenolic disinfectant. Influenza virus RNA was detected in at least one environmental sample from two of the three markets when tested by RRT-PCR; however, all samples were negative by virus isolation using the standard egg inoculation procedure. As a result of these findings, laboratory experiments were designed to evaluate several commonly used disinfectants for their ability to inactivate influenza as well as disrupt the RNA so that it could not be detected by the RRT-PCR test. Five disinfectants were tested: phenolic disinfectants (Tek-trol and one-stroke environ), a quaternary ammonia compound (Lysol no-rinse sanitizer), a peroxygen compound (Virkon-S), and sodium hypochlorite (household bleach). All five disinfectants were effective at inactivating AIV at the recommended concentrations, but AIV RNA in samples inactivated with phenolic and quaternary ammonia compounds could still be detected by RRT

  5. Assessment of the RNASound RNA Sampling Card for the preservation of influenza virus RNA

    Directory of Open Access Journals (Sweden)

    Hilda Lau

    2016-11-01

    Full Text Available Shipping influenza virus specimens, isolates or purified RNA is normally conducted at ultra-low temperatures using dry ice to ensure minimal degradation of the samples but this is expensive and requires special packaging and shipping conditions. Therefore, alternative methods for shipping influenza viruses or RNA at ambient temperatures would be desirable.The RNASound RNA Sampling Card (FortiusBio LLC, CA, USA is a device that enables specimens or isolates to be applied to a card, whereby viruses are inactivated, while RNA is preserved and purified RNA can also easily be eluted. To evaluate this card, we applied influenza virus cell culture isolate supernatants to either the RNASound card or Whatman Grade No. 1 filter paper (GE Healthcare, NSW, Australia and compared the preservation to that of material stored in liquid form. Preservation was tested using influenza A and B viruses at two different storage temperatures (cool 2-8oC or room temperature 18-22oC and these were compared with control material stored at -80°C, for 7, 14 or 28 days. The quality of the RNA recovered was assessed using real time RT-PCR and Sanger sequencing. The RNASound card was effective in preserving influenza RNA at room temperature for up to 28 days, with only a minor change in real-time RT-PCR cycle threshold values for selected gene targets when comparing between viruses applied to the card or stored at -80°C. Similar results were obtained with filter paper, whilst virus in liquid form performed the worst. Nevertheless, as the RNASound card also has the capability to inactivate viruses in addition to preserving RNA at room temperature for many weeks, this makes it feasible to send samples to laboratories using regular mail, and thus avoid the need for expensive shipping conditions requiring biohazard containers and dry ice. Moreover, the quick and simple RNA recovery from the RNASound card allows recipient labs to obtain RNA without the need for special reagents

  6. Invasive pneumococcal and meningococcal disease : association with influenza virus and respiratory syncytial virus activity?

    NARCIS (Netherlands)

    Jansen, A G S C; Sanders, E A M; VAN DER Ende, A; VAN Loon, A M; Hoes, A W; Hak, E

    2008-01-01

    Few studies have examined the relationship between viral activity and bacterial invasive disease, considering both influenza virus and respiratory syncytial virus (RSV). This study aimed to assess the potential relationship between invasive pneumococcal disease (IPD), meningococcal disease (MD), and

  7. Avian Influenza Virus (H5N1): a Threat to Human Health

    OpenAIRE

    Peiris, J. S. Malik; de Jong, Menno D.; Guan, Yi

    2007-01-01

    Pandemic influenza virus has its origins in avian influenza viruses. The highly pathogenic avian influenza virus subtype H5N1 is already panzootic in poultry, with attendant economic consequences. It continues to cross species barriers to infect humans and other mammals, often with fatal outcomes. Therefore, H5N1 virus has rightly received attention as a potential pandemic threat. However, it is noted that the pandemics of 1957 and 1968 did not arise from highly pathogenic influenza viruses, ...

  8. An Ultrasensitive Mechanism Regulates Influenza Virus-Induced Inflammation.

    Directory of Open Access Journals (Sweden)

    Jason E Shoemaker

    2015-06-01

    Full Text Available Influenza viruses present major challenges to public health, evident by the 2009 influenza pandemic. Highly pathogenic influenza virus infections generally coincide with early, high levels of inflammatory cytokines that some studies have suggested may be regulated in a strain-dependent manner. However, a comprehensive characterization of the complex dynamics of the inflammatory response induced by virulent influenza strains is lacking. Here, we applied gene co-expression and nonlinear regression analysis to time-course, microarray data developed from influenza-infected mouse lung to create mathematical models of the host inflammatory response. We found that the dynamics of inflammation-associated gene expression are regulated by an ultrasensitive-like mechanism in which low levels of virus induce minimal gene expression but expression is strongly induced once a threshold virus titer is exceeded. Cytokine assays confirmed that the production of several key inflammatory cytokines, such as interleukin 6 and monocyte chemotactic protein 1, exhibit ultrasensitive behavior. A systematic exploration of the pathways regulating the inflammatory-associated gene response suggests that the molecular origins of this ultrasensitive response mechanism lie within the branch of the Toll-like receptor pathway that regulates STAT1 phosphorylation. This study provides the first evidence of an ultrasensitive mechanism regulating influenza virus-induced inflammation in whole lungs and provides insight into how different virus strains can induce distinct temporal inflammation response profiles. The approach developed here should facilitate the construction of gene regulatory models of other infectious diseases.

  9. Interaction of influenza virus proteins with nucleosomes

    International Nuclear Information System (INIS)

    Garcia-Robles, Inmaculada; Akarsu, Hatice; Mueller, Christoph W.; Ruigrok, Rob W.H.; Baudin, Florence

    2005-01-01

    During influenza virus infection, transcription and replication of the viral RNA take place in the cell nucleus. Directly after entry in the nucleus the viral ribonucleoproteins (RNPs, the viral subunits containing vRNA, nucleoprotein and the viral polymerase) are tightly associated with the nuclear matrix. Here, we have analysed the binding of RNPs, M1 and NS2/NEP proteins to purified nucleosomes, reconstituted histone octamers and purified single histones. RNPs and M1 both bind to the chromatin components but at two different sites, RNP to the histone tails and M1 to the globular domain of the histone octamer. NS2/NEP did not bind to nucleosomes at all. The possible consequences of these findings for nuclear release of newly made RNPs and for other processes during the infection cycle are discussed

  10. Avian influenza virus risk assessment in falconry

    Directory of Open Access Journals (Sweden)

    Lüschow Dörte

    2011-04-01

    Full Text Available Abstract Background There is a continuing threat of human infections with avian influenza viruses (AIV. In this regard falconers might be a potential risk group because they have close contact to their hunting birds (raptors such as falcons and hawks as well as their avian prey such as gulls and ducks. Both (hunting birds and prey birds seem to be highly susceptible to some AIV strains, especially H5N1. We therefore conducted a field study to investigate AIV infections in falconers, their falconry birds as well as prey birds. Findings During 2 hunting seasons (2006/2007 and 2007/2008 falconers took tracheal and cloacal swabs from 1080 prey birds that were captured by their falconry birds (n = 54 in Germany. AIV-RNA of subtypes H6, H9, or H13 was detected in swabs of 4.1% of gulls (n = 74 and 3.8% of ducks (n = 53 using RT-PCR. The remaining 953 sampled prey birds and all falconry birds were negative. Blood samples of the falconry birds tested negative for AIV specific antibodies. Serum samples from all 43 falconers reacted positive in influenza A virus-specific ELISA, but remained negative using microneutralisation test against subtypes H5 and H7 and haemagglutination inhibition test against subtypes H6, H9 and H13. Conclusion Although we were able to detect AIV-RNA in samples from prey birds, the corresponding falconry birds and falconers did not become infected. Currently falconers do not seem to carry a high risk for getting infected with AIV through handling their falconry birds and their prey.

  11. Laser inactivation of pathogenic viruses in water

    Science.gov (United States)

    Grishkanich, Alexander; Zhevlakov, Alexander; Kascheev, Sergey; Sidorov, Igor; Ruzankina, Julia; Yakovlev, Alexey; Mak, Andrey

    2016-03-01

    Currently there is a situation that makes it difficult to provide the population with quality drinking water for the sanitary-hygienic requirements. One of the urgent problems is the need for water disinfection. Since the emergence of microorganisms that are pathogens transmitted through water such as typhoid, cholera, etc. requires constant cleansing of waters against pathogenic bacteria. In the water treatment process is destroyed up to 98% of germs, but among the remaining can be pathogenic viruses, the destruction of which requires special handling. As a result, the conducted research the following methods have been proposed for combating harmful microorganisms: sterilization of water by laser radiation and using a UV lamp.

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

    Directory of Open Access Journals (Sweden)

    Nuriban Valero-Pacheco

    Full Text Available 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.

  13. Avian influenza virus (H5N1; effects of physico-chemical factors on its survival

    Directory of Open Access Journals (Sweden)

    Hameed Sajid

    2009-03-01

    Full Text Available Abstract Present study was performed to determine the effects of physical and chemical agents on infective potential of highly pathogenic avian influenza (HPAI H5N1 (local strain virus recently isolated in Pakistan during 2006 outbreak. H5N1 virus having titer 108.3 ELD50/ml was mixed with sterilized peptone water to get final dilution of 4HA units and then exposed to physical (temperature, pH and ultraviolet light and chemical (formalin, phenol crystals, iodine crystals, CID 20, virkon®-S, zeptin 10%, KEPCIDE 300, KEPCIDE 400, lifebuoy, surf excel and caustic soda agents. Harvested amnio-allantoic fluid (AAF from embryonated chicken eggs inoculated with H5N1 treated virus (0.2 ml/egg was subjected to haemagglutination (HA and haemagglutination inhibition (HI tests. H5N1 virus lost infectivity after 30 min at 56°C, after 1 day at 28°C but remained viable for more than 100 days at 4°C. Acidic pH (1, 3 and basic pH (11, 13 were virucidal after 6 h contact time; however virus retained infectivity at pH 5 (18 h, 7 and 9 (more than 24 h. UV light was proved ineffectual in inactivating virus completely even after 60 min. Soap (lifebuoy®, detergent (surf excel® and alkali (caustic soda destroyed infectivity after 5 min at 0.1, 0.2 and 0.3% dilution. All commercially available disinfectants inactivated virus at recommended concentrations. Results of present study would be helpful in implementing bio-security measures at farms/hatcheries levels in the wake of avian influenza virus (AIV outbreak.

  14. High pressure processing's potential to inactivate norovirus and other fooodborne viruses

    Science.gov (United States)

    High pressure processing (HPP) can inactivate human norovirus. However, all viruses are not equally susceptible to HPP. Pressure treatment parameters such as required pressure levels, initial pressurization temperatures, and pressurization times substantially affect inactivation. How food matrix ...

  15. Reduction of Influenza Virus Titer and Protection against Influenza Virus Infection in Infant Mice Fed Lactobacillus casei Shirota

    OpenAIRE

    Yasui, Hisako; Kiyoshima, Junko; Hori, Tetsuji

    2004-01-01

    We investigated whether oral administration of Lactobacillus casei strain Shirota to neonatal and infant mice ameliorates influenza virus (IFV) infection in the upper respiratory tract and protects against influenza infection. In a model of upper respiratory IFV infection, the titer of virus in the nasal washings of infant mice administered L. casei Shirota (L. casei Shirota group) was significantly (P < 0.05) lower than that in infant mice administered saline (control group) (102.48 ± 100.31...

  16. Reassortant H1N1 influenza virus vaccines protect pigs against pandemic H1N1 influenza virus and H1N2 swine influenza virus challenge.

    Science.gov (United States)

    Yang, Huanliang; Chen, Yan; Shi, Jianzhong; Guo, Jing; Xin, Xiaoguang; Zhang, Jian; Wang, Dayan; Shu, Yuelong; Qiao, Chuanling; Chen, Hualan

    2011-09-28

    Influenza A (H1N1) virus has caused human influenza outbreaks in a worldwide pandemic since April 2009. Pigs have been found to be susceptible to this influenza virus under experimental and natural conditions, raising concern about their potential role in the pandemic spread of the virus. In this study, we generated a high-growth reassortant virus (SC/PR8) that contains the hemagglutinin (HA) and neuraminidase (NA) genes from a novel H1N1 isolate, A/Sichuan/1/2009 (SC/09), and six internal genes from A/Puerto Rico/8/34 (PR8) virus, by genetic reassortment. The immunogenicity and protective efficacy of this reassortant virus were evaluated at different doses in a challenge model using a homologous SC/09 or heterologous A/Swine/Guangdong/1/06(H1N2) virus (GD/06). Two doses of SC/PR8 virus vaccine elicited high-titer serum hemagglutination inhibiting (HI) antibodies specific for the 2009 H1N1 virus and conferred complete protection against challenge with either SC/09 or GD/06 virus, with reduced lung lesions and viral shedding in vaccine-inoculated animals compared with non-vaccinated control animals. These results indicated for the first time that a high-growth SC/PR8 reassortant H1N1 virus exhibits properties that are desirable to be a promising vaccine candidate for use in swine in the event of a pandemic H1N1 influenza. Copyright © 2011 Elsevier B.V. All rights reserved.

  17. Avian Influenza Virus Glycoproteins Restrict Virus Replication and Spread through Human Airway Epithelium at Temperatures of the Proximal Airways

    OpenAIRE

    Scull, Margaret A.; Gillim-Ross, Laura; Santos, Celia; Roberts, Kim L.; Bordonali, Elena; Subbarao, Kanta; Barclay, Wendy S.; Pickles, Raymond J.

    2009-01-01

    Transmission of avian influenza viruses from bird to human is a rare event even though avian influenza viruses infect the ciliated epithelium of human airways in vitro and ex vivo. Using an in vitro model of human ciliated airway epithelium (HAE), we demonstrate that while human and avian influenza viruses efficiently infect at temperatures of the human distal airways (37 degrees C), avian, but not human, influenza viruses are restricted for infection at the cooler temperatures of the human p...

  18. Genetic Analyses of an H3N8 Influenza Virus Isolate, Causative Strain of the Outbreak of Equine Influenza at the Kanazawa Racecourse in Japan in 2007.

    Science.gov (United States)

    Ito, Mika; Nagai, Makoto; Hayakawa, Yuji; Komae, Hirofumi; Murakami, Naruto; Yotsuya, Syouichi; Asakura, Shingo; Sakoda, Yoshihiro; Kida, Hiroshi

    2008-09-01

    In August 2007, an outbreak of equine influenza occurred among vaccinated racehorses with Japanese commercial equine influenza vaccine at Kanazawa Racecourse in Ishikawa prefecture in Japan. Apparent symptoms were pyrexia (38.2-41.0 degrees C) and nasal discharge with or without coughing, although approximately half of the infected horses were subclinical. All horses had been shot with a vaccine that contained two inactivated H3N8 influenza virus strains [A/equine/La Plata/93 (La Plata/93) of American lineage and A/equine/Avesta/93 (Avesta/93) of European lineage] and an H7N7 strain (A/equine/Newmarket/1/77). Influenza virus, A/equine/Kanazawa/1/2007 (H3N8) (Kanazawa/07), was isolated from one of the nasal swab samples of diseased horses. Phylogenetic analysis indicated that Kanazawa/07 was classified into the American sublineage Florida. In addition, four amino acid substitutions were found in the antigenic sites B and E in the HA1 subunit protein of Kanazawa/07 in comparison with that of La Plata/93. Hemagglutination-inhibition (HI) test using 16 serum samples from recovering horses revealed that 1.4- to 8-fold difference in titers between Kanazawa/07 and either of the vaccine strains. The present findings suggest that Japanese commercial inactivated vaccine contributed to reducing the morbidity rate and manifestation of the clinical signs of horses infected with Kanazawa/07 that may be antigenically different from the vaccine strains.

  19. The Influenza NS1 Protein: What Do We Know in Equine Influenza Virus Pathogenesis?

    Directory of Open Access Journals (Sweden)

    Marta Barba

    2016-08-01

    Full Text Available Equine influenza virus remains a serious health and potential economic problem throughout most parts of the world, despite intensive vaccination programs in some horse populations. The influenza non-structural protein 1 (NS1 has multiple functions involved in the regulation of several cellular and viral processes during influenza infection. We review the strategies that NS1 uses to facilitate virus replication and inhibit antiviral responses in the host, including sequestering of double-stranded RNA, direct modulation of protein kinase R activity and inhibition of transcription and translation of host antiviral response genes such as type I interferon. Details are provided regarding what it is known about NS1 in equine influenza, especially concerning C-terminal truncation. Further research is needed to determine the role of NS1 in equine influenza infection, which will help to understand the pathophysiology of complicated cases related to cytokine imbalance and secondary bacterial infection, and to investigate new therapeutic and vaccination strategies.

  20. A Defective Interfering Influenza RNA Inhibits Infectious Influenza Virus Replication in Human Respiratory Tract Cells: A Potential New Human Antiviral

    Directory of Open Access Journals (Sweden)

    Claire M. Smith

    2016-08-01

    Full Text Available Defective interfering (DI viruses arise during the replication of influenza A virus and contain a non-infective version of the genome that is able to interfere with the production of infectious virus. In this study we hypothesise that a cloned DI influenza A virus RNA may prevent infection of human respiratory epithelial cells with infection by influenza A. The DI RNA (244/PR8 was derived by a natural deletion process from segment 1 of influenza A/PR/8/34 (H1N1; it comprises 395 nucleotides and is packaged in the DI virion in place of a full-length genome segment 1. Given intranasally, 244/PR8 DI virus protects mice and ferrets from clinical influenza caused by a number of different influenza A subtypes and interferes with production of infectious influenza A virus in cells in culture. However, evidence that DI influenza viruses are active in cells of the human respiratory tract is lacking. Here we show that 244/PR8 DI RNA is replicated by an influenza A challenge virus in human lung diploid fibroblasts, bronchial epithelial cells, and primary nasal basal cells, and that the yield of challenge virus is significantly reduced in a dose-dependent manner indicating that DI influenza virus has potential as a human antiviral.

  1. The Role of Extracellular Histones in Influenza Virus Pathogenesis.

    Science.gov (United States)

    Ashar, Harshini K; Mueller, Nathan C; Rudd, Jennifer M; Snider, Timothy A; Achanta, Mallika; Prasanthi, Maram; Pulavendran, Sivasami; Thomas, Paul G; Ramachandran, Akhilesh; Malayer, Jerry R; Ritchey, Jerry W; Rajasekhar, Rachakatla; Chow, Vincent T K; Esmon, Charles T; Teluguakula, Narasaraju

    2018-01-01

    Although exaggerated host immune responses have been implicated in influenza-induced lung pathogenesis, the etiologic factors that contribute to these events are not completely understood. We previously demonstrated that neutrophil extracellular traps exacerbate pulmonary injury during influenza pneumonia. Histones are the major protein components of neutrophil extracellular traps and are known to have cytotoxic effects. Here, we examined the role of extracellular histones in lung pathogenesis during influenza. Mice infected with influenza virus displayed high accumulation of extracellular histones, with widespread pulmonary microvascular thrombosis. Occluded pulmonary blood vessels with vascular thrombi often exhibited endothelial necrosis surrounded by hemorrhagic effusions and pulmonary edema. Histones released during influenza induced cytotoxicity and showed strong binding to platelets within thrombi in infected mouse lungs. Nasal wash samples from influenza-infected patients also showed increased accumulation of extracellular histones, suggesting a possible clinical relevance of elevated histones in pulmonary injury. Although histones inhibited influenza growth in vitro, in vivo treatment with histones did not yield antiviral effects and instead exacerbated lung pathology. Blocking with antihistone antibodies caused a marked decrease in lung pathology in lethal influenza-challenged mice and improved protection when administered in combination with the antiviral agent oseltamivir. These findings support the pathogenic effects of extracellular histones in that pulmonary injury during influenza was exacerbated. Targeting histones provides a novel therapeutic approach to influenza pneumonia. Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  2. Newcastle disease virus-based H5 influenza vaccine protects chickens from lethal challenge with a highly pathogenic H5N2 avian influenza virus.

    Science.gov (United States)

    Ma, Jingjiao; Lee, Jinhwa; Liu, Haixia; Mena, Ignacio; Davis, A Sally; Sunwoo, Sun Young; Lang, Yuekun; Duff, Michael; Morozov, Igor; Li, Yuhao; Yang, Jianmei; García-Sastre, Adolfo; Richt, Juergen A; Ma, Wenjun

    2017-01-01

    Since December 2014, Eurasian-origin, highly pathogenic avian influenza H5 viruses including H5N1, H5N2, and H5N8 subtypes (called H5N x viruses), which belong to the H5 clade 2.3.4.4, have been detected in U.S. wild birds. Subsequently, highly pathogenic H5N2 and H5N8 viruses have caused outbreaks in U.S. domestic poultry. Vaccination is one of the most effective ways to control influenza outbreaks and protect animal and public health. Newcastle disease virus (NDV)-based influenza vaccines have been demonstrated to be efficacious and safe in poultry. Herein, we developed an NDV-based H5 vaccine (NDV-H5) that expresses a codon-optimized ectodomain of the hemagglutinin from the A/chicken/Iowa/04-20/2015 (H5N2) virus and evaluated its efficacy in chickens. Results showed that both live and inactivated NDV-H5 vaccines induced hemagglutinin inhibition antibody titers against the H5N2 virus in immunized chickens after prime and booster, and both NDV-H5 vaccines completely protected chickens from lethal challenge with the highly pathogenic H5N2 A/turkey/Minnesota/9845-4/2015 virus. No clinical signs and only minimal virus shedding was observed in both vaccinated groups. In contrast, all mock-vaccinated, H5N2-infected chickens shed virus and died within 5 days post challenge. Furthermore, one dose of the live NDV-H5 vaccine also provided protection of 90% chickens immunized by coarse spraying; after exposure to H5N2 challenge, sera from vaccinated surviving chickens neutralized both highly pathogenic H5N1 and H5N8 viruses. Taken together, our results suggest that the NDV-based H5 vaccine is able to protect chickens against intercontinental highly pathogenic H5N x viruses and can be used by mass application to protect the poultry industry.

  3. A novel, colorimetric neutralization assay for measuring antibodies to influenza viruses.

    Science.gov (United States)

    Lehtoranta, Liisa; Villberg, Anja; Santanen, Riitta; Ziegler, Thedi

    2009-08-01

    A colorimetric cell proliferation assay for measuring neutralizing antibodies to influenza viruses in human sera is described. Following a 90-min incubation, the serum-virus mixture was transferred to Madin-Darby canine kidney cells cultured in 96-well plates. After further incubation for three days, a tetrazolium salt was added to the wells. Cellular mitochondrial dehydrogenases cleave the tetrazolium salt to formazan, and the resulting color change is read by a spectrophotometer. The absorbance values correlate directly to the number of viable cells in the assay well and thus also to the neutralizing activity of influenza-specific antibodies present in the serum. With the few hands-on manipulations required, this assay allows simultaneous testing of a considerable number of sera, offers opportunities for automation, and is suitable for use under biosafety level-3 conditions. The test was used to study the antibody response after the administration of seasonal, inactivated, trivalent influenza vaccine. Antibody titers determined by the neutralization test in pre- and post-vaccination serum pairs were compared with those obtained by the hemagglutination inhibition assay. The neutralization test yielded higher pre- and post-vaccination titers and a larger number of significant increases in post-vaccination antibody titer than the hemagglutination inhibition test. This new test format could serve as a valuable laboratory tool for influenza vaccine studies.

  4. Rapid detection of the avian influenza virus H5N1 subtype in Egypt

    African Journals Online (AJOL)

    Dr

    highly pathogenic avian influenza virus subtype H5N1 in Egypt is threatening poultry and ... Key words: Avian influenza virus, H5N1, fluorescent antibody enzyme-linked immunosorbent assay (ELISA) ..... poultry and is potentially zoonotic.

  5. Novel reassortant swine influenza viruses are circulating in Danish pigs

    DEFF Research Database (Denmark)

    Breum, Solvej Østergaard; Hjulsager, Charlotte Kristiane; Trebbien, Ramona

    of the reassortant viruses comprised a HA gene similar to H1 of H1N1 avian-like swine influenza virus (SIV) and a NA gene most closely related to N2 gene of human H3N2 influenza virus that circulated in humans in the mid 1990s. The internal genes of this reassortant virus with the subtype H1avN2hu all belonged...... to the H1N1 avian-like SIV lineages. Until now this novel virus H1avN2hu has only been detected in Danish swine. The other novel reassortant virus contained the HA gene from H1N1pdm09 virus and a NA gene similar to the N2 gene of H3N2 SIV that have been circulating in European swine since the mid 1980s...

  6. Evaluation of recombinant influenza virus-simian immunodeficiency virus vaccines in macaques.

    Science.gov (United States)

    Sexton, Amy; De Rose, Robert; Reece, Jeanette C; Alcantara, Sheilajen; Loh, Liyen; Moffat, Jessica M; Laurie, Karen; Hurt, Aeron; Doherty, Peter C; Turner, Stephen J; Kent, Stephen J; Stambas, John

    2009-08-01

    There is an urgent need for human immunodeficiency virus (HIV) vaccines that induce robust mucosal immunity. Influenza A viruses (both H1N1 and H3N2) were engineered to express simian immunodeficiency virus (SIV) CD8 T-cell epitopes and evaluated following administration to the respiratory tracts of 11 pigtail macaques. Influenza virus was readily detected from respiratory tract secretions, although the infections were asymptomatic. Animals seroconverted to influenza virus and generated CD8 and CD4 T-cell responses to influenza virus proteins. SIV-specific CD8 T-cell responses bearing the mucosal homing marker beta7 integrin were induced by vaccination of naïve animals. Further, SIV-specific CD8 T-cell responses could be boosted by recombinant influenza virus-SIV vaccination of animals with already-established SIV infection. Sequential vaccination with influenza virus-SIV recombinants of different subtypes (H1N1 followed by H3N2 or vice versa) produced only a limited boost in immunity, probably reflecting T-cell immunity to conserved internal proteins of influenza A virus. SIV challenge of macaques vaccinated with an influenza virus expressing a single SIV CD8 T cell resulted in a large anamnestic recall CD8 T-cell response, but immune escape rapidly ensued and there was no impact on chronic SIV viremia. Although our results suggest that influenza virus-HIV vaccines hold promise for the induction of mucosal immunity to HIV, broader antigen cover will be needed to limit cytotoxic T-lymphocyte escape.

  7. Inactivated Influenza Vaccine That Provides Rapid, Innate-Immune-System-Mediated Protection and Subsequent Long-Term Adaptive Immunity.

    Science.gov (United States)

    Chua, Brendon Y; Wong, Chinn Yi; Mifsud, Edin J; Edenborough, Kathryn M; Sekiya, Toshiki; Tan, Amabel C L; Mercuri, Francesca; Rockman, Steve; Chen, Weisan; Turner, Stephen J; Doherty, Peter C; Kelso, Anne; Brown, Lorena E; Jackson, David C

    2015-10-27

    The continual threat to global health posed by influenza has led to increased efforts to improve the effectiveness of influenza vaccines for use in epidemics and pandemics. We show in this study that formulation of a low dose of inactivated detergent-split influenza vaccine with a Toll-like receptor 2 (TLR2) agonist-based lipopeptide adjuvant (R4Pam2Cys) provides (i) immediate, antigen-independent immunity mediated by the innate immune system and (ii) significant enhancement of antigen-dependent immunity which exhibits an increased breadth of effector function. Intranasal administration of mice with vaccine formulated with R4Pam2Cys but not vaccine alone provides protection against both homologous and serologically distinct (heterologous) viral strains within a day of administration. Vaccination in the presence of R4Pam2Cys subsequently also induces high levels of systemic IgM, IgG1, and IgG2b antibodies and pulmonary IgA antibodies that inhibit hemagglutination (HA) and neuraminidase (NA) activities of homologous but not heterologous virus. Improved primary virus nucleoprotein (NP)-specific CD8(+) T cell responses are also induced by the use of R4Pam2Cys and are associated with robust recall responses to provide heterologous protection. These protective effects are demonstrated in wild-type and antibody-deficient animals but not in those depleted of CD8(+) T cells. Using a contact-dependent virus transmission model, we also found that heterologous virus transmission from vaccinated mice to naive mice is significantly reduced. These results demonstrate the potential of adding a TLR2 agonist to an existing seasonal influenza vaccine to improve its utility by inducing immediate short-term nonspecific antiviral protection and also antigen-specific responses to provide homologous and heterologous immunity. The innate and adaptive immune systems differ in mechanisms, specificities, and times at which they take effect. The innate immune system responds within hours of

  8. Serum-free microcarrier based production of replication deficient Influenza vaccine candidate virus lacking NS1 using Vero cells

    Directory of Open Access Journals (Sweden)

    Yan Mylene L

    2011-08-01

    Full Text Available Abstract Background Influenza virus is a major health concern that has huge impacts on the human society, and vaccination remains as one of the most effective ways to mitigate this disease. Comparing the two types of commercially available Influenza vaccine, the live attenuated virus vaccine is more cross-reactive and easier to administer than the traditional inactivated vaccines. One promising live attenuated Influenza vaccine that has completed Phase I clinical trial is deltaFLU, a deletion mutant lacking the viral Nonstructural Protein 1 (NS1 gene. As a consequence of this gene deletion, this mutant virus can only propagate effectively in cells with a deficient interferon-mediated antiviral response. To demonstrate the manufacturability of this vaccine candidate, a batch bioreactor production process using adherent Vero cells on microcarriers in commercially available animal-component free, serum-free media is described. Results Five commercially available animal-component free, serum-free media (SFM were evaluated for growth of Vero cells in agitated Cytodex 1 spinner flask microcarrier cultures. EX-CELL Vero SFM achieved the highest cell concentration of 2.6 × 10^6 cells/ml, whereas other SFM achieved about 1.2 × 10^6 cells/ml. Time points for infection between the late exponential and stationary phases of cell growth had no significant effect in the final virus titres. A virus yield of 7.6 Log10 TCID50/ml was achieved using trypsin concentration of 10 μg/ml and MOI of 0.001. The Influenza vaccine production process was scaled up to a 3 liter controlled stirred tank bioreactor to achieve a cell density of 2.7 × 10^6 cells/ml and virus titre of 8.3 Log10 TCID50/ml. Finally, the bioreactor system was tested for the production of the corresponding wild type H1N1 Influenza virus, which is conventionally used in the production of inactivated vaccine. High virus titres of up to 10 Log10 TCID50/ml were achieved. Conclusions We describe for the

  9. Humans and ferrets with prior H1N1 influenza virus infections do not exhibit evidence of original antigenic sin after infection or vaccination with the 2009 pandemic H1N1 influenza virus.

    Science.gov (United States)

    O'Donnell, Christopher D; Wright, Amber; Vogel, Leatrice; Boonnak, Kobporn; Treanor, John J; Subbarao, Kanta

    2014-05-01

    The hypothesis of original antigenic sin (OAS) states that the imprint established by an individual's first influenza virus infection governs the antibody response thereafter. Subsequent influenza virus infection results in an antibody response against the original infecting virus and an impaired immune response against the newer influenza virus. The purpose of our study was to seek evidence of OAS after infection or vaccination with the 2009 pandemic H1N1 (2009 pH1N1) virus in ferrets and humans previously infected with H1N1 viruses with various antigenic distances from the 2009 pH1N1 virus, including viruses from 1935 through 1999. In ferrets, seasonal H1N1 priming did not diminish the antibody response to infection or vaccination with the 2009 pH1N1 virus, nor did it diminish the T-cell response, indicating the absence of OAS in seasonal H1N1 virus-primed ferrets. Analysis of paired samples of human serum taken before and after vaccination with a monovalent inactivated 2009 pH1N1 vaccine showed a significantly greater-fold rise in the titer of antibody against the 2009 pH1N1 virus than against H1N1 viruses that circulated during the childhood of each subject. Thus, prior experience with H1N1 viruses did not result in an impairment of the antibody response against the 2009 pH1N1 vaccine. Our data from ferrets and humans suggest that prior exposure to H1N1 viruses did not impair the immune response against the 2009 pH1N1 virus.

  10. Chimeric Hemagglutinin Constructs Induce Broad Protection against Influenza B Virus Challenge in the Mouse Model.

    Science.gov (United States)

    Ermler, Megan E; Kirkpatrick, Ericka; Sun, Weina; Hai, Rong; Amanat, Fatima; Chromikova, Veronika; Palese, Peter; Krammer, Florian

    2017-06-15

    Seasonal influenza virus epidemics represent a significant public health burden. Approximately 25% of all influenza virus infections are caused by type B viruses, and these infections can be severe, especially in children. Current influenza virus vaccines are an effective prophylaxis against infection but are impacted by rapid antigenic drift, which can lead to mismatches between vaccine strains and circulating strains. Here, we describe a broadly protective vaccine candidate based on chimeric hemagglutinins, consisting of globular head domains from exotic influenza A viruses and stalk domains from influenza B viruses. Sequential vaccination with these constructs in mice leads to the induction of broadly reactive antibodies that bind to the conserved stalk domain of influenza B virus hemagglutinin. Vaccinated mice are protected from lethal challenge with diverse influenza B viruses. Results from serum transfer experiments and antibody-dependent cell-mediated cytotoxicity (ADCC) assays indicate that this protection is antibody mediated and based on Fc effector functions. The present data suggest that chimeric hemagglutinin-based vaccination is a viable strategy to broadly protect against influenza B virus infection. IMPORTANCE While current influenza virus vaccines are effective, they are affected by mismatches between vaccine strains and circulating strains. Furthermore, the antiviral drug oseltamivir is less effective for treating influenza B virus infections than for treating influenza A virus infections. A vaccine that induces broad and long-lasting protection against influenza B viruses is therefore urgently needed. Copyright © 2017 American Society for Microbiology.

  11. No serological evidence that harbour porpoises are additional hosts of influenza B viruses.

    Directory of Open Access Journals (Sweden)

    Rogier Bodewes

    Full Text Available Influenza A and B viruses circulate among humans causing epidemics almost annually. While various hosts for influenza A viruses exist, influenza B viruses have been detected only in humans and seals. However, recurrent infections of seals in Dutch coastal waters with influenza B viruses that are antigenetically distinct from influenza B viruses circulating among humans suggest that influenza B viruses have been introduced into this seal population by another, non-human, host. Harbour porpoises (Phocoena phocoena are sympatric with seals in these waters and are also occasionally in close contact with humans after stranding and subsequent rehabilitation. In addition, virus attachment studies demonstrated that influenza B viruses can bind to cells of the respiratory tract of these animals. Therefore, we hypothesized that harbour porpoises might be a reservoir of influenza B viruses. In the present study, an unique set of serum samples from 79 harbour porpoises, stranded alive on the Dutch coast between 2003 and 2013, was tested for the presence of antibodies against influenza B viruses by use of the hemagglutination inhibition test and for antibodies against influenza A viruses by use of a competitive influenza A nucleoprotein ELISA. No antibodies were detected against either virus, suggesting that influenza A and B virus infections of harbour porpoises in Dutch coastal waters are not common, which was supported by statistical analysis of the dataset.

  12. Influenza B virus M2 protein can functionally replace its influenza A virus counterpart in promoting virus replication

    International Nuclear Information System (INIS)

    Wanitchang, Asawin; Wongthida, Phonphimon; Jongkaewwattana, Anan

    2016-01-01

    The M2 protein (AM2 and BM2) of influenza A and B viruses function as a proton channel essential for viral replication. They also carry a cytoplasmic tail whose functions are not fully delineated. It is currently unknown whether these proteins could be replaced functionally in a viral context. Here, we generated single-cycle influenza A viruses (scIAV-ΔHA) carrying various M2-2A-mCherry constructs in the segment 4 (HA) and evaluated their growth in complementing cells. Intriguingly, the scIAV-ΔHA carrying AM2 and that bearing BM2 grew comparably well in MDCK-HA cells. Furthermore, while the virus carrying chimeric B-AM2 in which the BM2 transmembrane fused with the AM2 cytoplasmic tail produced robust infection, the one bearing the AM2 transmembrane fused with the BM2 cytoplasmic tail (A-BM2) exhibited severely impaired growth. Altogether, we demonstrate that AM2 and BM2 are functionally interchangeable and underscore the role of compatibility between transmembrane and cytoplasmic tail of the M2 protein. -- Highlights: •Flu A M2 protein (AM2) can be functionally replaced by that of Flu B (BM2). •Both AM2 and BM2 with extended cytoplasmic tail are functional. •Compatibility between the ion channel and the cytoplasmic tail is critical for M2 function. •M2 with higher ion channel activity may augment influenza virus replication.

  13. Influenza B virus M2 protein can functionally replace its influenza A virus counterpart in promoting virus replication

    Energy Technology Data Exchange (ETDEWEB)

    Wanitchang, Asawin; Wongthida, Phonphimon; Jongkaewwattana, Anan, E-mail: anan.jon@biotec.or.th

    2016-11-15

    The M2 protein (AM2 and BM2) of influenza A and B viruses function as a proton channel essential for viral replication. They also carry a cytoplasmic tail whose functions are not fully delineated. It is currently unknown whether these proteins could be replaced functionally in a viral context. Here, we generated single-cycle influenza A viruses (scIAV-ΔHA) carrying various M2-2A-mCherry constructs in the segment 4 (HA) and evaluated their growth in complementing cells. Intriguingly, the scIAV-ΔHA carrying AM2 and that bearing BM2 grew comparably well in MDCK-HA cells. Furthermore, while the virus carrying chimeric B-AM2 in which the BM2 transmembrane fused with the AM2 cytoplasmic tail produced robust infection, the one bearing the AM2 transmembrane fused with the BM2 cytoplasmic tail (A-BM2) exhibited severely impaired growth. Altogether, we demonstrate that AM2 and BM2 are functionally interchangeable and underscore the role of compatibility between transmembrane and cytoplasmic tail of the M2 protein. -- Highlights: •Flu A M2 protein (AM2) can be functionally replaced by that of Flu B (BM2). •Both AM2 and BM2 with extended cytoplasmic tail are functional. •Compatibility between the ion channel and the cytoplasmic tail is critical for M2 function. •M2 with higher ion channel activity may augment influenza virus replication.

  14. Control of Influenza and Poliomyelitis with Killed Virus Vaccines

    Science.gov (United States)

    Salk, Jonas; Salk, Darrell

    1977-01-01

    Discusses control of poliomyelitis and influenza by live and killed virus vaccines. Considered are the etiological agents, pathogenic mechanisms and epidemiology of each disease. Reviews recent scientific studies of the diseases. Recommends use of killed virus vaccines in controlling both diseases. (CS)

  15. Avian influenza A viruses: From zoonosis to pandemic

    NARCIS (Netherlands)

    M. Richard (Mathilde); M.T. de Graaf (Marieke); S. Herfst (Sander)

    2014-01-01

    textabstractZoonotic influenza A viruses originating from the animal reservoir pose a threat for humans, as they have the ability to trigger pandemics upon adaptation to and invasion of an immunologically naive population. Of particular concern are the H5N1 viruses that continue to circulate in

  16. Rapidly expanding range of highly pathogenic avian influenza viruses

    Science.gov (United States)

    Hall, Jeffrey S.; Dusek, Robert J.; Spackman, Erica

    2015-01-01

    The movement of highly pathogenic avian influenza (H5N8) virus across Eurasia and into North America and the virus’ propensity to reassort with co-circulating low pathogenicity viruses raise concerns among poultry producers, wildlife biologists, aviculturists, and public health personnel worldwide. Surveillance, modeling, and experimental research will provide the knowledge required for intelligent policy and management decisions.

  17. Avian influenza a virus budding morphology: spherical or filamentous?

    Science.gov (United States)

    Most strains of influenza A virus (IAV) can produce long (µm length) filamentous virus particles as well as ~100 nm diameter spherical virions. The function of the filamentous particles is unclear but is hypothesized to facilitate transmission within or from the respiratory tract. In mammalian IAVs,...

  18. Transmission of highly pathogenic avian influenza H7 virus

    NARCIS (Netherlands)

    Bos, M.E.H.

    2009-01-01

    Knowledge of the transmission of highly pathogenic avian influenza (HPAI) virus still has gaps, complicating epidemic control. A model was developed to back-calculate the day HPAI virus was introduced into a flock, based on within-flock mortality data of the Dutch HPAI H7N7 epidemic (2003). The

  19. Influenza virus and endothelial cells: A species specific relationship

    NARCIS (Netherlands)

    K.R. Short (Kirsty); E.J.B. Veldhuis Kroeze (Edwin); L.A. Reperant (Leslie); M. Richard (Mathilde); T. Kuiken (Thijs)

    2014-01-01

    textabstractInfluenza A virus (IAV) infection is an important cause of respiratory disease in humans. The original reservoirs of IAV are wild waterfowl and shorebirds, where virus infection causes limited, if any, disease. Both in humans and in wild waterbirds, epithelial cells are the main target

  20. Influenza and other respiratory viruses in three Central American countries

    Science.gov (United States)

    Laguna‐Torres, Victor A.; Sánchez‐Largaespada, José F.; Lorenzana, Ivette; Forshey, Brett; Aguilar, Patricia; Jimenez, Mirna; Parrales, Eduardo; Rodriguez, Francisco; García, Josefina; Jimenez, Ileana; Rivera, Maribel; Perez, Juan; Sovero, Merly; Rios, Jane; Gamero, María E.; Halsey, Eric S.; Kochel, Tadeusz J.

    2010-01-01

    Please cite this paper as: Laguna‐Torres et al. (2011) Influenza and other respiratory viruses in three Central American countries. Influenza and Other Respiratory Viruses 5(2), 123–134. Background  Despite the disease burden imposed by respiratory diseases on children in Central America, there is a paucity of data describing the etiologic agents of the disease. Aims  To analyze viral etiologic agents associated with influenza‐like illness (ILI) in participants reporting to one outpatient health center, one pediatric hospital, and three general hospitals in El Salvador, Honduras, and Nicaragua Material & Methods  Between August 2006 and April 2009, pharyngeal swabs were collected from outpatients and inpatients. Patient specimens were inoculated onto cultured cell monolayers, and viral antigens were detected by indirect and direct immunofluorescence staining. Results  A total of 1,756 patients were enrolled, of whom 1,195 (68.3%) were under the age of 5; and 183 (10.4%) required hospitalization. One or more viral agents were identified in 434 (24.7%) cases, of which 17 (3.9%) were dual infections. The most common viruses isolated were influenza A virus (130; 7.4% of cases), respiratory syncytial virus (122; 6.9%), adenoviruses (63; 3.6%), parainfluenza viruses (57; 3.2%), influenza B virus (47; 2.7% of cases), and herpes simplex virus 1 (22; 1.3%). In addition, human metapneumovirus and enteroviruses (coxsackie and echovirus) were isolated from patient specimens. Discussion  When compared to the rest of the population, viruses were isolated from a significantly higher percentage of patients age 5 or younger. The prevalence of influenza A virus or influenza B virus infections was similar between the younger and older age groups. RSV was the most commonly detected pathogen in infants age 5 and younger and was significantly associated with pneumonia (p < 0.0001) and hospitalization (p < 0.0001). Conclusion  Genetic analysis of influenza

  1. Influenza virus neutralizing antibodies and IgG isotype profiles after immunization of mice with influenza A subunit vaccine using various adjuvants

    NARCIS (Netherlands)

    Benne, CA; Harmsen, M; vanderGraaff, W; Verheul, AFM; Snippe, H; Kraaijeveld, CA

    The influence of various adjuvants on the development of influenza virus neutralizing antibodies and distribution of anti-influenza virus IgG isotypes after immunization of mice with influenza A (H3N2) subunit vaccine was investigated. Serum titres of influenza virus neutralizing antibodies and

  2. Cloned defective interfering influenza virus protects ferrets from pandemic 2009 influenza A virus and allows protective immunity to be established.

    Directory of Open Access Journals (Sweden)

    Nigel J Dimmock

    Full Text Available Influenza A viruses are a major cause of morbidity and mortality in the human population, causing epidemics in the winter, and occasional worldwide pandemics. In addition there are periodic outbreaks in domestic poultry, horses, pigs, dogs, and cats. Infections of domestic birds can be fatal for the birds and their human contacts. Control in man operates through vaccines and antivirals, but both have their limitations. In the search for an alternative treatment we have focussed on defective interfering (DI influenza A virus. Such a DI virus is superficially indistinguishable from a normal virus but has a large deletion in one of the eight RNAs that make up the viral genome. Antiviral activity resides in the deleted RNA. We have cloned one such highly active DI RNA derived from segment 1 (244 DI virus and shown earlier that intranasal administration protects mice from lethal disease caused by a number of different influenza A viruses. A more cogent model of human influenza is the ferret. Here we found that intranasal treatment with a single dose of 2 or 0.2 µg 244 RNA delivered as A/PR/8/34 virus particles protected ferrets from disease caused by pandemic virus A/California/04/09 (A/Cal; H1N1. Specifically, 244 DI virus significantly reduced fever, weight loss, respiratory symptoms, and infectious load. 244 DI RNA, the active principle, was amplified in nasal washes following infection with A/Cal, consistent with its amelioration of clinical disease. Animals that were treated with 244 DI RNA cleared infectious and DI viruses without delay. Despite the attenuation of infection and disease by DI virus, ferrets formed high levels of A/Cal-specific serum haemagglutination-inhibiting antibodies and were solidly immune to rechallenge with A/Cal. Together with earlier data from mouse studies, we conclude that 244 DI virus is a highly effective antiviral with activity potentially against all influenza A subtypes.

  3. Chiropteran influenza viruses: flu from bats or a relic from the past?

    Science.gov (United States)

    Brunotte, Linda; Beer, Martin; Horie, Masayuki; Schwemmle, Martin

    2016-02-01

    The identification of influenza A-like genomic sequences in bats suggests the existence of distinct lineages of chiropteran influenza viruses in South and Central America. These viruses share similarities with conventional influenza A viruses but lack the canonical receptor-binding property and neuraminidase function. The inability to isolate infectious bat influenza viruses impeded further studies, however, reverse genetic analysis provided new insights into the molecular biology of these viruses. In this review, we highlight the recent developments in the field of the newly discovered bat-derived influenza A-like viruses. We also discuss whether bats are a neglected natural reservoir of influenza viruses, the risk associated with bat influenza viruses for humans and whether these viruses originate from the pool of avian IAV or vice versa. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Influenza-Like Illnesses in Senegal: Not Only Focus on Influenza Viruses

    Science.gov (United States)

    Dia, Ndongo; Diene Sarr, Fatoumata; Thiam, Diamilatou; Faye Sarr, Tening; Espié, Emmanuelle; OmarBa, Ibrahim; Coly, Malang; Niang, Mbayame; Richard, Vincent

    2014-01-01

    Influenza surveillance in African countries was initially restricted to the identification of circulating strains. In Senegal, the network has recently been enhanced (i) to include epidemiological data from Dakar and other regions and (ii) to extend virological surveillance to other respiratory viruses. Epidemiological data from the sentinel sites is transmitted daily by mobile phone. The data include those for other febrile syndromes similar to influenza-like illnesses (ILI), corresponding to integrated approach. Also, clinical samples are randomly selected and analyzed for influenza and other respiratory viruses. There were 101,640 declared visits to the 11 sentinel sites between week 11-2012 and week 35-2013; 22% of the visits were for fever syndromes and 23% of the cases of fever syndrome were ILI. Influenza viruses were the second most frequent cause of ILI (20%), after adenoviruses (21%) and before rhinoviruses (18%) and enteroviruses (15%). Co-circulation and co-infection were frequent and were responsible for ILI peaks. The first months of implementation of the enhanced surveillance system confirmed that viruses other the influenza make large contributions to influenza-like illnesses. It is therefore important to consider these etiologies in the development of strategies to reduce respiratory infections. More informative tools and research studies are required to assess the burden of respiratory infections in developing countries. PMID:24675982

  5. Avian Influenza Virus A (H5N1), Detected through Routine Surveillance, in Child, Bangladesh

    Science.gov (United States)

    Alamgir, A.S.M.; Sultana, Rebecca; Islam, M. Saiful; Rahman, Mustafizur; Fry, Alicia M.; Shu, Bo; Lindstrom, Stephen; Nahar, Kamrun; Goswami, Doli; Haider, M. Sabbir; Nahar, Sharifun; Butler, Ebonee; Hancock, Kathy; Donis, Ruben O.; Davis, Charles T.; Zaman, Rashid Uz; Luby, Stephen P.; Uyeki, Timothy M.; Rahman, Mahmudur

    2009-01-01

    We identified avian influenza virus A (H5N1) infection in a child in Bangladesh in 2008 by routine influenza surveillance. The virus was of the same clade and phylogenetic subgroup as that circulating among poultry during the period. This case illustrates the value of routine surveillance for detection of novel influenza virus. PMID:19751601

  6. Avian influenza virus (H5N1): a threat to human health

    NARCIS (Netherlands)

    Peiris, J. S. Malik; de Jong, Menno D.; Guan, Yi

    2007-01-01

    Pandemic influenza virus has its origins in avian influenza viruses. The highly pathogenic avian influenza virus subtype H5N1 is already panzootic in poultry, with attendant economic consequences. It continues to cross species barriers to infect humans and other mammals, often with fatal outcomes.

  7. Inactivation of infectious bovine rhinotracheitis virus by gamma irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Nonomiya, Takashi; Yamashiro, Tomio; Tsutsumi, Takamasa (Animal Quarantine Service, Yokohama (Japan)); Ito, Hitoshi; Ishigaki, Isao

    1990-10-01

    Radiation inactivation of Infectious Boivne Rhinotracheitis (IBR) virus was investigated by suspending in a commercial preparation medium (c.p.m.) or IBR antibody free serum and irradiated at room temperature or dry ice frozen condition. Normal pooled serum was also analysed by electrophoresis with cellulose acetate membrane after irradiation at frozen and non-frozen condition. The virus inactivation was determined by MDBK cell line which 50 % tissue culture infectious dose (TCID{sub 50}) was calculated by Behrens Kaerber method. D{sub 10} value at non-frozen condition in serum was obtained as 1.1-1.2 kGy and that in c.p.m. was 1.3-1.4 kGy. On the other hand, D{sub 10} value was increased to 3.4-3.6 kGy in serum and 3.9 kGy in c.p.m. at frozen condition. On the irradiation effect of bovine serum, four peaks of albumin, {alpha}, {beta} and {gamma}-globulin fraction were obtained from non-irradiation and irradiated serum up to 2 kGy at non-frozen condition by electrophoresis. More than 4 kGy irradiation, the peaks of globulin fractions became not clear and at more than 8 kGy, changed to one large peak. On the other hand, these changes of electrophoretic patterns were not observed even at 30 kGy irradiation in frozen condition. From these results, necessary dose was decided as 20-25 kGy at frozen condition for inactivation of IBR virus in serum. (author).

  8. Inactivation of infectious bovine rhinotracheitis virus by gamma irradiation

    International Nuclear Information System (INIS)

    Nonomiya, Takashi; Yamashiro, Tomio; Tsutsumi, Takamasa; Ito, Hitoshi; Ishigaki, Isao.

    1990-01-01

    Radiation inactivation of Infectious Boivne Rhinotracheitis (IBR) virus was investigated by suspending in a commercial preparation medium (c.p.m.) or IBR antibody free serum and irradiated at room temperature or dry ice frozen condition. Normal pooled serum was also analysed by electrophoresis with cellulose acetate membrane after irradiation at frozen and non-frozen condition. The virus inactivation was determined by MDBK cell line which 50 % tissue culture infectious dose (TCID 50 ) was calculated by Behrens Kaerber method. D 10 value at non-frozen condition in serum was obtained as 1.1-1.2 kGy and that in c.p.m. was 1.3-1.4 kGy. On the other hand, D 10 value was increased to 3.4-3.6 kGy in serum and 3.9 kGy in c.p.m. at frozen condition. On the irradiation effect of bovine serum, four peaks of albumin, α, β and γ-globulin fraction were obtained from non-irradiation and irradiated serum up to 2 kGy at non-frozen condition by electrophoresis. More than 4 kGy irradiation, the peaks of globulin fractions became not clear and at more than 8 kGy, changed to one large peak. On the other hand, these changes of electrophoretic patterns were not observed even at 30 kGy irradiation in frozen condition. From these results, necessary dose was decided as 20-25 kGy at frozen condition for inactivation of IBR virus in serum. (author)

  9. Influenza A Viruses of Human Origin in Swine, Brazil.

    Science.gov (United States)

    Nelson, Martha I; Schaefer, Rejane; Gava, Danielle; Cantão, Maurício Egídio; Ciacci-Zanella, Janice Reis

    2015-08-01

    The evolutionary origins of the influenza A(H1N1)pdm09 virus that caused the first outbreak of the 2009 pandemic in Mexico remain unclear, highlighting the lack of swine surveillance in Latin American countries. Although Brazil has one of the largest swine populations in the world, influenza was not thought to be endemic in Brazil's swine until the major outbreaks of influenza A(H1N1)pdm09 in 2009. Through phylogenetic analysis of whole-genome sequences of influenza viruses of the H1N1, H1N2, and H3N2 subtypes collected in swine in Brazil during 2009-2012, we identified multiple previously uncharacterized influenza viruses of human seasonal H1N2 and H3N2 virus origin that have circulated undetected in swine for more than a decade. Viral diversity has further increased in Brazil through reassortment between co-circulating viruses, including A(H1N1)pdm09. The circulation of multiple divergent hemagglutinin lineages challenges the design of effective cross-protective vaccines and highlights the need for additional surveillance.

  10. Influenza A Viruses of Human Origin in Swine, Brazil

    Science.gov (United States)

    Schaefer, Rejane; Gava, Danielle; Cantão, Maurício Egídio; Ciacci-Zanella, Janice Reis

    2015-01-01

    The evolutionary origins of the influenza A(H1N1)pdm09 virus that caused the first outbreak of the 2009 pandemic in Mexico remain unclear, highlighting the lack of swine surveillance in Latin American countries. Although Brazil has one of the largest swine populations in the world, influenza was not thought to be endemic in Brazil’s swine until the major outbreaks of influenza A(H1N1)pdm09 in 2009. Through phylogenetic analysis of whole-genome sequences of influenza viruses of the H1N1, H1N2, and H3N2 subtypes collected in swine in Brazil during 2009–2012, we identified multiple previously uncharacterized influenza viruses of human seasonal H1N2 and H3N2 virus origin that have circulated undetected in swine for more than a decade. Viral diversity has further increased in Brazil through reassortment between co-circulating viruses, including A(H1N1)pdm09. The circulation of multiple divergent hemagglutinin lineages challenges the design of effective cross-protective vaccines and highlights the need for additional surveillance. PMID:26196759

  11. Detecting emerging transmissibility of avian influenza virus in human households.

    Directory of Open Access Journals (Sweden)

    Michiel van Boven

    2007-07-01

    Full Text Available Accumulating infections of highly pathogenic H5N1 avian influenza in humans underlines the need to track the ability of these viruses to spread among humans. A human-transmissible avian influenza virus is expected to cause clusters of infections in humans living in close contact. Therefore, epidemiological analysis of infection clusters in human households is of key importance. Infection clusters may arise from transmission events from (i the animal reservoir, (ii humans who were infected by animals (primary human-to-human transmission, or (iii humans who were infected by humans (secondary human-to-human transmission. Here we propose a method of analysing household infection data to detect changes in the transmissibility of avian influenza viruses in humans at an early stage. The method is applied to an outbreak of H7N7 avian influenza virus in The Netherlands that was the cause of more than 30 human-to-human transmission events. The analyses indicate that secondary human-to-human transmission is plausible for the Dutch household infection data. Based on the estimates of the within-household transmission parameters, we evaluate the effectiveness of antiviral prophylaxis, and conclude that it is unlikely that all household infections can be prevented with current antiviral drugs. We discuss the applicability of our method for the detection of emerging human-to-human transmission of avian influenza viruses in particular, and for the analysis of within-household infection data in general.

  12. Inactivated Eyedrop Influenza Vaccine Adjuvanted with Poly(I:C Is Safe and Effective for Inducing Protective Systemic and Mucosal Immunity.

    Directory of Open Access Journals (Sweden)

    Eun-Do Kim

    Full Text Available The eye route has been evaluated as an efficient vaccine delivery routes. However, in order to induce sufficient antibody production with inactivated vaccine, testing of the safety and efficacy of the use of inactivated antigen plus adjuvant is needed. Here, we assessed various types of adjuvants in eyedrop as an anti-influenza serum and mucosal Ab production-enhancer in BALB/c mice. Among the adjuvants, poly (I:C showed as much enhancement in antigen-specific serum IgG and mucosal IgA antibody production as cholera toxin (CT after vaccinations with trivalent hemagglutinin-subunits or split H1N1 vaccine antigen in mice. Vaccination with split H1N1 eyedrop vaccine antigen plus poly(I:C showed a similar or slightly lower efficacy in inducing antibody production than intranasal vaccination; the eyedrop vaccine-induced immunity was enough to protect mice from lethal homologous influenza A/California/04/09 (H1N1 virus challenge. Additionally, ocular inoculation with poly(I:C plus vaccine antigen generated no signs of inflammation within 24 hours: no increases in the mRNA expression levels of inflammatory cytokines nor in the infiltration of mononuclear cells to administration sites. In contrast, CT administration induced increased expression of IL-6 cytokine mRNA and mononuclear cell infiltration in the conjunctiva within 24 hours of vaccination. Moreover, inoculated visualizing materials by eyedrop did not contaminate the surface of the olfactory bulb in mice; meanwhile, intranasally administered materials defiled the surface of the brain. On the basis of these findings, we propose that the use of eyedrop inactivated influenza vaccine plus poly(I:C is a safe and effective mucosal vaccine strategy for inducing protective anti-influenza immunity.

  13. Avian Influenza A Viruses: Evolution and Zoonotic Infection.

    Science.gov (United States)

    Kim, Se Mi; Kim, Young-Il; Pascua, Philippe Noriel Q; Choi, Young Ki

    2016-08-01

    Although efficient human-to-human transmission of avian influenza virus has yet to be seen, in the past two decades avian-to-human transmission of influenza A viruses has been reported. Influenza A/H5N1, in particular, has repeatedly caused human infections associated with high mortality, and since 1998 the virus has evolved into many clades of variants with significant antigenic diversity. In 2013, three (A/H7N9, A/H6N1, and A/H10N8) novel avian influenza viruses (AIVs) breached the animal-human host species barrier in Asia. In humans, roughly 35% of A/H7N9-infected patients succumbed to the zoonotic infection, and two of three A/H10N8 human infections were also lethal; however, neither of these viruses cause influenza-like symptoms in poultry. While most of these cases were associated with direct contact with infected poultry, some involved sustained human-to-human transmission. Thus, these events elicited concern regarding potential AIV pandemics. This article reviews the human incursions associated with AIV variants and the potential role of pigs as an intermediate host that may hasten AIV evolution. In addition, we discuss the known influenza A virus virulence and transmission factors and their evaluation in animal models. With the growing number of human AIV infections, constant vigilance for the emergence of novel viruses is of utmost importance. In addition, careful characterization and pathobiological assessment of these novel variants will help to identify strains of particular concern for future pandemics. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  14. Development of methods to measure virus inactivation in fresh waters.

    Science.gov (United States)

    Ward, R L; Winston, P E

    1985-11-01

    This study concerns the identification and correction of deficiencies in methods used to measure inactivation rates of enteric viruses seeded into environmental waters. It was found that viable microorganisms in an environmental water sample increased greatly after addition of small amounts of nutrients normally present in the unpurified seed virus preparation. This burst of microbial growth was not observed after seeding the water with purified virus. The use of radioactively labeled poliovirus revealed that high percentages of virus particles, sometimes greater than 99%, were lost through adherence to containers, especially in less turbid waters. This effect was partially overcome by the use of polypropylene containers and by the absence of movement during incubation. Adherence to containers clearly demonstrated the need for labeled viruses to monitor losses in this type of study. Loss of viral infectivity in samples found to occur during freezing was avoided by addition of broth. Finally, microbial contamination of the cell cultures during infectivity assays was overcome by the use of gentamicin and increased concentrations of penicillin, streptomycin, and amphotericin B.

  15. Vaxtracker: Active on-line surveillance for adverse events following inactivated influenza vaccine in children.

    Science.gov (United States)

    Cashman, Patrick; Moberley, Sarah; Dalton, Craig; Stephenson, Jody; Elvidge, Elissa; Butler, Michelle; Durrheim, David N

    2014-09-22

    Vaxtracker is a web based survey for active post marketing surveillance of Adverse Events Following Immunisation. It is designed to efficiently monitor vaccine safety of new vaccines by early signal detection of serious adverse events. The Vaxtracker system automates contact with the parents or carers of immunised children by email and/or sms message to their smart phone. A hyperlink on the email and text messages links to a web based survey exploring adverse events following the immunisation. The Vaxtracker concept was developed during 2011 (n=21), and piloted during the 2012 (n=200) and 2013 (n=477) influenza seasons for children receiving inactivated influenza vaccine (IIV) in the Hunter New England Local Health District, New South Wales, Australia. Survey results were reviewed by surveillance staff to detect any safety signals and compare adverse event frequencies among the different influenza vaccines administered. In 2012, 57% (n=113) of the 200 participants responded to the online survey and 61% (290/477) in 2013. Vaxtracker appears to be an effective method for actively monitoring adverse events following influenza vaccination in children. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

  16. Serum amyloid P component inhibits influenza A virus infections: in vitro and in vivo studies

    DEFF Research Database (Denmark)

    Horvath, A; Andersen, I; Junker, K

    2001-01-01

    . These studies were extended to comprise five mouse-adapted influenza A strains, two swine influenza A strains, a mink influenza A virus, a ferret influenza A reassortant virus, a influenza B virus and a parainfluenza 3 virus. The HA activity of all these viruses was inhibited by SAP. Western blotting showed......Serum amyloid P component (SAP) binds in vitro Ca(2+)-dependently to several ligands including oligosaccharides with terminal mannose and galactose. We have earlier reported that SAP binds to human influenza A virus strains, inhibiting hemagglutinin (HA) activity and virus infectivity in vitro...... that SAP bound to HA trimers, monomers and HA1 and HA2 subunits of influenza A virus. Binding studies indicated that galactose, mannose and fucose moieties contributed to the SAP reacting site(s). Intranasal administration of human SAP to mice induced no demonstrable toxic reactions, and circulating...

  17. Influence of pH, Salt and Temperature on Pressure Inactivation of Hepatitis A virus

    Science.gov (United States)

    The effects of pH (3-7), NaCl (0-6%), and temperature on pressure inactivation of hepatitis A virus (HAV) were determined. The HAV samples were treated at 400 MPa for 1 min at 5, 20, and 50C. Decreasing solution pH enhanced pressure inactivation of HAV. This enhanced inactivation effect was most e...

  18. The inactivation of hepatitis A virus and other model viruses by UV irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Battigelli, D A; Sobsey, M D; Lobe, D C [North Carolina Univ., Chapel Hill, NC (United States). Dept. of Environmental Sciences

    1993-01-01

    Ultraviolet light is an attractive alternative to chemical disinfection of water, but little is known about its ability to inactivate important waterborne pathogens such as hepatitis A virus. Therefore, the sensitivity of HAV strain HM-175, coxsackievirus type B-5, rotavirus strain SA-11, and bacteriophages MS2 and [phi]X174 to ultraviolet radiation of 254 nm wavelength in phosphate buffered water was determined. Purified stocks of the viruses were combined and exposed to collimated UV radiation in a stirred reactor for a total dose of up to 40 mW sec/cm[sup 2]. Virus survival kinetics were determined from samples removed at dose intervals. The results of these experiments indicate that UV radiation can effectively inactivate viruses of public health concern in drinking water. (author).

  19. The inactivation of hepatitis A virus and other model viruses by UV irradiation

    International Nuclear Information System (INIS)

    Battigelli, D.A.; Sobsey, M.D.; Lobe, D.C.

    1993-01-01

    Ultraviolet light is an attractive alternative to chemical disinfection of water, but little is known about its ability to inactivate important waterborne pathogens such as hepatitis A virus. Therefore, the sensitivity of HAV strain HM-175, coxsackievirus type B-5, rotavirus strain SA-11, and bacteriophages MS2 and φX174 to ultraviolet radiation of 254 nm wavelength in phosphate buffered water was determined. Purified stocks of the viruses were combined and exposed to collimated UV radiation in a stirred reactor for a total dose of up to 40 mW sec/cm 2 . Virus survival kinetics were determined from samples removed at dose intervals. The results of these experiments indicate that UV radiation can effectively inactivate viruses of public health concern in drinking water. (author)

  20. Animal Models for Influenza Viruses: Implications for Universal Vaccine Development

    Directory of Open Access Journals (Sweden)

    Irina Margine

    2014-10-01

    Full Text Available Influenza virus infections are a significant cause of morbidity and mortality in the human population. Depending on the virulence of the influenza virus strain, as well as the immunological status of the infected individual, the severity of the respiratory disease may range from sub-clinical or mild symptoms to severe pneumonia that can sometimes lead to death. Vaccines remain the primary public health measure in reducing the influenza burden. Though the first influenza vaccine preparation was licensed more than 60 years ago, current research efforts seek to develop novel vaccination strategies with improved immunogenicity, effectiveness, and breadth of protection. Animal models of influenza have been essential in facilitating studies aimed at understanding viral factors that affect pathogenesis and contribute to disease or transmission. Among others, mice, ferrets, pigs, and nonhuman primates have been used to study influenza virus infection in vivo, as well as to do pre-clinical testing of novel vaccine approaches. Here we discuss and compare the unique advantages and limitations of each model.

  1. Incorporation of membrane-bound, mammalian-derived immunomodulatory proteins into influenza whole virus vaccines boosts immunogenicity and protection against lethal challenge

    Directory of Open Access Journals (Sweden)

    Roberts Paul C

    2009-04-01

    Full Text Available Abstract Background Influenza epidemics continue to cause morbidity and mortality within the human population despite widespread vaccination efforts. This, along with the ominous threat of an avian influenza pandemic (H5N1, demonstrates the need for a much improved, more sophisticated influenza vaccine. We have developed an in vitro model system for producing a membrane-bound Cytokine-bearing Influenza Vaccine (CYT-IVAC. Numerous cytokines are involved in directing both innate and adaptive immunity and it is our goal to utilize the properties of individual cytokines and other immunomodulatory proteins to create a more immunogenic vaccine. Results We have evaluated the immunogenicity of inactivated cytokine-bearing influenza vaccines using a mouse model of lethal influenza virus challenge. CYT-IVACs were produced by stably transfecting MDCK cell lines with mouse-derived cytokines (GM-CSF, IL-2 and IL-4 fused to the membrane-anchoring domain of the viral hemagglutinin. Influenza virus replication in these cell lines resulted in the uptake of the bioactive membrane-bound cytokines during virus budding and release. In vivo efficacy studies revealed that a single low dose of IL-2 or IL-4-bearing CYT-IVAC is superior at providing protection against lethal influenza challenge in a mouse model and provides a more balanced Th1/Th2 humoral immune response, similar to live virus infections. Conclusion We have validated the protective efficacy of CYT-IVACs in a mammalian model of influenza virus infection. This technology has broad applications in current influenza virus vaccine development and may prove particularly useful in boosting immune responses in the elderly, where current vaccines are minimally effective.

  2. Inactivated Recombinant Rabies Viruses Displaying Canine Distemper Virus Glycoproteins Induce Protective Immunity against Both Pathogens

    OpenAIRE

    da Fontoura Budaszewski, Renata; Hudacek, Andrew; Sawatsky, Bevan; Krämer, Beate; Yin, Xiangping; Schnell, Matthias J.; von Messling, Veronika

    2017-01-01

    The development of multivalent vaccines is an attractive methodology for the simultaneous prevention of several infectious diseases in vulnerable populations. Both canine distemper virus (CDV) and rabies virus (RABV) cause lethal disease in wild and domestic carnivores. While RABV vaccines are inactivated, the live-attenuated CDV vaccines retain residual virulence for highly susceptible wildlife species. In this study, we developed recombinant bivalent vaccine candidates based on recombinant ...

  3. In Vivo Imaging of Influenza Virus Infection in Immunized Mice

    Directory of Open Access Journals (Sweden)

    Rita Czakó

    2017-05-01

    Full Text Available Immunization is the cornerstone of seasonal influenza control and represents an important component of pandemic preparedness strategies. Using a bioluminescent reporter virus, we demonstrate the application of noninvasive in vivo imaging system (IVIS technology to evaluate the preclinical efficacy of candidate vaccines and immunotherapy in a mouse model of influenza. Sequential imaging revealed distinct spatiotemporal kinetics of bioluminescence in groups of mice passively or actively immunized by various strategies that accelerated the clearance of the challenge virus at different rates and by distinct mechanisms. Imaging findings were consistent with conclusions derived from virus titers in the lungs and, notably, were more informative than conventional efficacy endpoints in some cases. Our findings demonstrate the reliability of IVIS as a qualitative approach to support preclinical evaluation of candidate medical countermeasures for influenza in mice.

  4. Hsp90 inhibitors reduce influenza virus replication in cell culture

    International Nuclear Information System (INIS)

    Chase, Geoffrey; Deng, Tao; Fodor, Ervin; Leung, B.W.; Mayer, Daniel; Schwemmle, Martin; Brownlee, George

    2008-01-01

    The viral RNA polymerase complex of influenza A virus consists of three subunits PB1, PB2 and PA. Recently, the cellular chaperone Hsp90 was shown to play a role in nuclear import and assembly of the trimeric polymerase complex by binding to PB1 and PB2. Here we show that Hsp90 inhibitors, geldanamycin or its derivative 17-AAG, delay the growth of influenza virus in cell culture resulting in a 1-2 log reduction in viral titre early in infection. We suggest that this is caused by the reduced half-life of PB1 and PB2 and inhibition of nuclear import of PB1 and PA which lead to reduction in viral RNP assembly. Hsp90 inhibitors may represent a new class of antiviral compounds against influenza viruses

  5. [Exploration on mechanism of anti-influenza virus activity of genus Paeonia based on network pharmacology].

    Science.gov (United States)

    Cai, Ya-Qi; Bao, Ya-Ting; Wang, Hong-Jin; Ren, Xiao-Dong; Huang, Lin-Fang; He, Jie; Liu, Tian-Tian; Zeng, Rui

    2018-04-01

    This paper aimed to investigate the anti-influenza virus activity of the genus Paeonia, screen potential anti-influenza virus compounds and predict targets of anti-influenza virus to explore the mechanism of anti-influenza virus activity. First of all, a total of 301 compounds of the genus Paeonia were summarized from the literatures in recent ten years. The candidate active ingredients from the genus Paeonia were identified by database such as PubChem and Chemical Book. The ligands were constructed by ChemDraw, Avogadro and Discovery Studio Visualizer. Secondly, 23 potential anti-influenza virus targets were developed by combining the target database and the literatures. Uniprot database was used to find the anti-influenza virus targets, and RCSB was used to identify targets associated with anti-influenza virus activity as docked receptor proteins. QuickVina 2.0 software was used for molecular docking. Finally, the Cytoscape 3.5.1 software was used to map the potential activity compounds of the genus Paeonia against influenza virus and the anti-influenza virus target network. Uniprot online database was used to analyze the target GO enrichment and KEGG metabolic pathways. The results showed that 74 compounds of the genus Paeonia had anti-influenza virus effect and 18 potential anti-influenza virus targets were screened. GO analysis concluded that the mechanism of the genus Paeonia anti-influenza virus is consistent with the mechanism of NA anti-influenza virus in order to stop the sprouting, dispersion and diffusion of virus and reduce the ability of virus to infect, so that the infection can be restricted so as to achieve the anti-influenza virus effect. Copyright© by the Chinese Pharmaceutical Association.

  6. Universal Detection and Identification of Avian Influenza Virus by Use of Resequencing Microarrays

    Science.gov (United States)

    2009-04-01

    Recent outbreaks of Nipah virus , severe acute respiratory syndrome virus , and avian influenza virus reiterate the impor- tance of zoonotic microbes as...Society for Microbiology. All Rights Reserved. Universal Detection and Identification of Avian Influenza Virus by Use of Resequencing Microarrays...been, and continue to emerge as, threats to human health. The recent outbreaks of highly pathogenic avian influenza virus in bird populations and the

  7. Strengthening the influenza vaccine virus selection and development process: Report of the 3rd WHO Informal Consultation for Improving Influenza Vaccine Virus Selection held at WHO headquarters, Geneva, Switzerland, 1-3 April 2014.

    Science.gov (United States)

    Ampofo, William K; Azziz-Baumgartner, Eduardo; Bashir, Uzma; Cox, Nancy J; Fasce, Rodrigo; Giovanni, Maria; Grohmann, Gary; Huang, Sue; Katz, Jackie; Mironenko, Alla; Mokhtari-Azad, Talat; Sasono, Pretty Multihartina; Rahman, Mahmudur; Sawanpanyalert, Pathom; Siqueira, Marilda; Waddell, Anthony L; Waiboci, Lillian; Wood, John; Zhang, Wenqing; Ziegler, Thedi

    2015-08-26

    investigations but could drive a new surveillance paradigm. However, despite the advances made, significant challenges will need to be addressed before next-generation technologies become routine, particularly in low-resource settings. Emerging approaches and techniques such as synthetic genomics, systems genetics, systems biology and mathematical modelling are capable of generating potentially huge volumes of highly complex and diverse datasets. Harnessing the currently theoretical benefits of such bioinformatics ("big data") concepts for the influenza vaccine virus selection and development process will depend upon further advances in data generation, integration, analysis and dissemination. Over the last decade, growing awareness of influenza as an important global public health issue has been coupled to ever-increasing demands from the global community for more-equitable access to effective and affordable influenza vaccines. The current influenza vaccine landscape continues to be dominated by egg-based inactivated and live attenuated vaccines, with a small number of cell-based and recombinant vaccines. Successfully completing each step in the annual influenza vaccine manufacturing cycle will continue to rely upon timely and regular communication between the WHO GISRS, manufacturers and regulatory authorities. While the pipeline of influenza vaccines appears to be moving towards a variety of niche products in the near term, it is apparent that the ultimate aim remains the development of effective "universal" influenza vaccines that offer longer-lasting immunity against a broad range of influenza A subtypes. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. Interspecies Interactions and Potential Influenza A Virus Risk in Small Swine Farms in Peru

    Science.gov (United States)

    2012-03-15

    and swine influenza viruses : our current understanding of the zoonotic risk. Vet Res 2007, 38(2):243–260. 4. Wertheim JO: When pigs fly: the avian ...first authors. Abstract Background The recent avian influenza epidemic in Asia and the H1N1 pandemic demonstrated that influenza A viruses pose a...prime “mixing vessels” due to the dual receptivity of their trachea to human and avian strains. Additionally, avian and human influenza viruses

  9. A Novel H1N2 Influenza Virus Related to the Classical and Human Influenza Viruses from Pigs in Southern China

    OpenAIRE

    Song, Yafen; Wu, Xiaowei; Wang, Nianchen; Ouyang, Guowen; Qu, Nannan; Cui, Jin; Qi, Yan; Liao, Ming; Jiao, Peirong

    2016-01-01

    Southern China has long been considered to be an epicenter of pandemic influenza viruses. The special environment, breeding mode, and lifestyle in southern China provides more chances for wild aquatic birds, domestic poultry, pigs, and humans to be in contact. This creates the opportunity for interspecies transmission and generation of new influenza viruses. In this study, we reported a novel reassortant H1N2 influenza virus from pigs in southern China. According to the phylogenetic trees and...

  10. Infection and Replication of Influenza Virus at the Ocular Surface.

    Science.gov (United States)

    Creager, Hannah M; Kumar, Amrita; Zeng, Hui; Maines, Taronna R; Tumpey, Terrence M; Belser, Jessica A

    2018-04-01

    Although influenza viruses typically cause respiratory tract disease, some viruses, particularly those with an H7 hemagglutinin, have been isolated from the eyes of conjunctivitis cases. Previous work has shown that isolates of multiple subtypes from both ocular and respiratory infections are capable of replication in human ex vivo ocular tissues and corneal or conjunctival cell monolayers, leaving the determinants of ocular tropism unclear. Here, we evaluated the effect of several variables on tropism for ocular cells cultured in vitro and examined the potential effect of the tear film on viral infectivity. All viruses tested were able to replicate in primary human corneal epithelial cell monolayers subjected to aerosol inoculation. The temperature at which cells were cultured postinoculation minimally affected infectivity. Replication efficiency, in contrast, was reduced at 33°C relative to that at 37°C, and this effect was slightly greater for the conjunctivitis isolates than for the respiratory ones. With the exception of a seasonal H3N2 virus, the subset of viruses studied in multilayer corneal tissue constructs also replicated productively after either aerosol or liquid inoculation. Human tears significantly inhibited the hemagglutination of both ocular and nonocular isolates, but the effect on viral infectivity was more variable, with tears reducing the infectivity of nonocular isolates more than ocular isolates. These data suggest that most influenza viruses may be capable of establishing infection if they reach the surface of ocular cells but that this is more likely for ocular-tropic viruses, as they are better able to maintain their infectivity during passage through the tear film. IMPORTANCE The potential spread of zoonotic influenza viruses to humans represents an important threat to public health. Unfortunately, despite the importance of cellular and tissue tropism to pathogenesis, determinants of influenza virus tropism have yet to be fully

  11. White spot syndrome virus inactivation study by using gamma irradiation

    Science.gov (United States)

    Heidareh, Marzieh; Sedeh, Farahnaz Motamedi; Soltani, Mehdi; Rajabifar, Saeed; Afsharnasab, Mohammad; Dashtiannasab, Aghil

    2014-09-01

    The present study was conducted to investigate the effect of gamma irradiation on white spot syndrome virus (WSSV). White spot syndrome virus is a pathogen of major economic importance in cultured penaeid shrimp industries. White spot disease can cause mortalities reaching 100% within 3-10 days of gross signs appearing. During the period of culture, immunostimulant agents and vaccines may provide potential methods to protect shrimps from opportunistic and pathogenic microrganisms. In this study, firstly, WSSV was isolated from infected shrimp and then multiplied in crayfish. WSSV was purified from the infected crayfish haemolymph by sucrose gradient and confirmed by transmission electron microscopy. In vivo virus titration was performed in shrimp, Penaeus semisulcatus. The LD50 of live virus stock was calculated 10 5.4/mL. Shrimp post-larvae (1-2 g) were treated with gamma-irradiated (different doses) WSSV (100 to 10-4 dilutions) for a period of 10 days. The dose/survival curve for irradiated and un-irradiated WSSV was drawn; the optimum dose range for inactivation of WSSV and unaltered antigenicity was obtained 14-15 kGy. This preliminary information suggests that shrimp appear to benefit from treatment with gammairradiated WSSV especially at 14-15 KGy.

  12. Photodynamic inactivation of bacteria and viruses using two monosubstituted zinc(II) phthalocyanines.

    Science.gov (United States)

    Ke, Mei-Rong; Eastel, Jennifer Mary; Ngai, Karry L K; Cheung, Yuk-Yam; Chan, Paul K S; Hui, Mamie; Ng, Dennis K P; Lo, Pui-Chi

    2014-09-12

    A zinc(II) phthalocyanine substituted with a triamino moiety and its tri-N-methylated analogue have been prepared and characterized with various spectroscopic methods. Both compounds remain non-aggregated in N,N-dimethylformamide and in water containing 0.05% Cremophor EL (v/v), and can generate singlet oxygen effectively. The photodynamic activities of these compounds have been examined against a range of bacterial strains, including the Gram-positive methicillin-sensitive Staphylococcus aureus ATCC 25923 and methicillin-resistant Staphylococcus aureus ATCC BAA-43, and the Gram-negative Escherichia coli ATCC 35218 and Pseudomonas aeruginosa ATCC 27853. Both photosensitizers are highly cytotoxic, particularly for the two Gram-positive strains, for which as low as 5 nM of dye is required to induce a 4-log reduction of their viability. The tri-N-methylated derivative has also been shown to be able to effectively inhibit the growth of a series of clinical strains of Staphylococcus aureus and Escherichia coli, and biofilms of methicillin-resistant Staphylococcus aureus ATCC 67928 and ATCC 68507, and Staphylococcus epidermidis ATCC 35984. In addition, the photodynamic inactivation of a range of viruses using these two compounds has also been investigated. Both compounds are highly photocytotoxic against the enveloped viruses influenza A virus (H1N1) and herpes simplex virus type 1 (HSV1), but exhibit no significant cytotoxicity toward the non-enveloped viruses adenovirus type 3 (Ad3) and coxsackievirus (Cox B1). Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  13. Inactivated Recombinant Rabies Viruses Displaying Canine Distemper Virus Glycoproteins Induce Protective Immunity against Both Pathogens.

    Science.gov (United States)

    da Fontoura Budaszewski, Renata; Hudacek, Andrew; Sawatsky, Bevan; Krämer, Beate; Yin, Xiangping; Schnell, Matthias J; von Messling, Veronika

    2017-04-15

    The development of multivalent vaccines is an attractive methodology for the simultaneous prevention of several infectious diseases in vulnerable populations. Both canine distemper virus (CDV) and rabies virus (RABV) cause lethal disease in wild and domestic carnivores. While RABV vaccines are inactivated, the live-attenuated CDV vaccines retain residual virulence for highly susceptible wildlife species. In this study, we developed recombinant bivalent vaccine candidates based on recombinant vaccine strain rabies virus particles, which concurrently display the protective CDV and RABV glycoprotein antigens. The recombinant viruses replicated to near-wild-type titers, and the heterologous glycoproteins were efficiently expressed and incorporated in the viral particles. Immunization of ferrets with beta-propiolactone-inactivated recombinant virus particles elicited protective RABV antibody titers, and animals immunized with a combination of CDV attachment protein- and fusion protein-expressing recombinant viruses were protected from lethal CDV challenge. However, animals that were immunized with only a RABV expressing the attachment protein of CDV vaccine strain Onderstepoort succumbed to infection with a more recent wild-type strain, indicating that immune responses to the more conserved fusion protein contribute to protection against heterologous CDV strains. IMPORTANCE Rabies virus and canine distemper virus (CDV) cause high mortality rates and death in many carnivores. While rabies vaccines are inactivated and thus have an excellent safety profile and high stability, live-attenuated CDV vaccines can retain residual virulence in highly susceptible species. Here we generated recombinant inactivated rabies viruses that carry one of the CDV glycoproteins on their surface. Ferrets immunized twice with a mix of recombinant rabies viruses carrying the CDV fusion and attachment glycoproteins were protected from lethal CDV challenge, whereas all animals that received

  14. Human milk lactoferrin inactivates two putative colonization factors expressed by Haemophilus influenzae.

    Science.gov (United States)

    Qiu, J; Hendrixson, D R; Baker, E N; Murphy, T F; St Geme, J W; Plaut, A G

    1998-10-13

    Haemophilus influenzae is a major cause of otitis media and other respiratory tract disease in children. The pathogenesis of disease begins with colonization of the upper respiratory mucosa, a process that involves evasion of local immune mechanisms and adherence to epithelial cells. Several studies have demonstrated that human milk is protective against H. influenzae colonization and disease. In the present study, we examined the effect of human milk on the H. influenzae IgA1 protease and Hap adhesin, two autotransported proteins that are presumed to facilitate colonization. Our results demonstrated that human milk lactoferrin efficiently extracted the IgA1 protease preprotein from the bacterial outer membrane. In addition, lactoferrin specifically degraded the Hap adhesin and abolished Hap-mediated adherence. Extraction of IgA1 protease and degradation of Hap were localized to the N-lobe of the bilobed lactoferrin molecule and were inhibited by serine protease inhibitors, suggesting that the lactoferrin N-lobe may contain serine protease activity. Additional experiments revealed no effect of lactoferrin on the H. influenzae P2, P5, and P6 outer-membrane proteins, which are distinguished from IgA1 protease and Hap by the lack of an N-terminal passenger domain or an extracellular linker region. These results suggest that human milk lactoferrin may attenuate the pathogenic potential of H. influenzae by selectively inactivating IgA1 protease and Hap, thereby interfering with colonization. Future studies should examine the therapeutic potential of lactoferrin, perhaps as a supplement in infant formulas.

  15. Efficacy of Live-Attenuated H9N2 Influenza Vaccine Candidates Containing NS1 Truncations against H9N2 Avian Influenza Viruses

    Directory of Open Access Journals (Sweden)

    Sujuan Chen

    2017-06-01

    Full Text Available H9N2 avian influenza virus is a zoonotic agent with a broad host range that can contribute genetic information to H5 or H7N9 subtype viruses, which are significant threats to both humans and birds. Thus, there is a great need for a vaccine to control H9N2 avian influenza. Three mutant viruses of an H9N2 virus A/chicken/Taixing/10/2010 (rTX-NS1-73, rTX-NS1-100, and rTX-NS1-128 were constructed with different NS1 gene truncations and confirmed by western blot analysis. The genetic stability, pathogenicity, transmissibility, and host immune responses toward these mutants were evaluated. The mutant virus rTX-NS1-128 exhibited the most attenuated phenotype and lost transmissibility. The expression levels of interleukin 12 in the nasal and tracheal tissues from chickens immunized with rTX-NS1-128 were significantly upregulated on day 3 post-immunization and the IgA and IgG antibody levels were significantly increased on days 7, 14, and 21 post-immunization when compared to chickens that received an inactivated vaccine. rTX-NS1-128 also protected chickens from challenge by homologous and heterologous H9N2 avian influenza viruses. The results indicate that rTX-NS1-128 can be used as a potential live-attenuated vaccine against H9N2 avian influenza.

  16. Swine Influenza Virus Antibodies in Humans, Western Europe, 2009

    Science.gov (United States)

    Gerloff, Nancy A.; Kremer, Jacques R.; Charpentier, Emilie; Sausy, Aurélie; Olinger, Christophe M.; Weicherding, Pierre; Schuh, John; Van Reeth, Kristien

    2011-01-01

    Serologic studies for swine influenza viruses (SIVs) in humans with occupational exposure to swine have been reported from the Americas but not from Europe. We compared levels of neutralizing antibodies against 3 influenza viruses—pandemic (H1N1) 2009, an avian-like enzootic subtype H1N1 SIV, and a 2007–08 seasonal subtype H1N1—in 211 persons with swine contact and 224 matched controls in Luxembourg. Persons whose profession involved contact with swine had more neutralizing antibodies against SIV and pandemic (H1N1) 2009 virus than did the controls. Controls also had antibodies against these viruses although exposure to them was unlikely. Antibodies against SIV and pandemic (H1N1) 2009 virus correlated with each other but not with seasonal subtype H1N1 virus. Sequential exposure to variants of seasonal influenza (H1N1) viruses may have increased chances for serologic cross-reactivity with antigenically distinct viruses. Further studies are needed to determine the extent to which serologic responses correlate with infection. PMID:21392430

  17. Membrane-bound IL-12 and IL-23 serve as potent mucosal adjuvants when co-presented on whole inactivated influenza vaccines.

    Science.gov (United States)

    Khan, Tila; Heffron, Connie L; High, Kevin P; Roberts, Paul C

    2014-05-03

    Potent and safe adjuvants are needed to improve the efficacy of parenteral and mucosal vaccines. Cytokines, chemokines and growth factors have all proven to be effective immunomodulatory adjuvants when administered with a variety of antigens. We have previously evaluated the efficacy of membrane-anchored interleukins (IL) such as IL-2 and IL-4 co-presented as Cytokine-bearing Influenza Vaccines (CYT-IVACs) using a mouse model of influenza challenge. Here, we describe studies evaluating the parenteral and mucosal adjuvanticity of membrane-bound IL-12 and IL-23 CYT-IVACs in young adult mice. Mucosal immunization using IL-12 and IL-23 bearing whole influenza virus vaccine (WIV) was more effective at eliciting virus-specific nasal IgA and reducing viral lung burden following challenge compared to control WIV vaccinated animals. Both IL-12 and IL-23 bearing WIV elicited the highest anti-viral IgA levels in serum and nasal washes. This study highlights for the first time the mucosal adjuvant potential of IL-12 and IL-23 CYT-IVAC formulations in eliciting mucosal immune responses and reducing viral lung burden. The co-presentation of immunomodulators in direct context with viral antigen in whole inactivated viral vaccines may provide a means to significantly lower the dose of vaccine required for protection.

  18. Influenza A(H9N2) Virus, Myanmar, 2014-2015.

    Science.gov (United States)

    Lin, Thant Nyi; Nonthabenjawan, Nutthawan; Chaiyawong, Supassama; Bunpapong, Napawan; Boonyapisitsopa, Supanat; Janetanakit, Taveesak; Mon, Pont Pont; Mon, Hla Hla; Oo, Kyaw Naing; Oo, Sandi Myint; Mar Win, Mar; Amonsin, Alongkorn

    2017-06-01

    Routine surveillance of influenza A virus was conducted in Myanmar during 2014-2015. Influenza A(H9N2) virus was isolated in Shan State, upper Myanmar. Whole-genome sequencing showed that H9N2 virus from Myanmar was closely related to H9N2 virus of clade 4.2.5 from China.

  19. A combination in-ovo vaccine for avian influenza virus and Newcastle disease virus.

    Science.gov (United States)

    Steel, John; Burmakina, Svetlana V; Thomas, Colleen; Spackman, Erica; García-Sastre, Adolfo; Swayne, David E; Palese, Peter

    2008-01-24

    The protection of poultry from H5N1 highly pathogenic avian influenza A (HPAI) and Newcastle disease virus (NDV) can be achieved through vaccination, as part of a broader disease control strategy. We have previously generated a recombinant influenza virus expressing, (i) an H5 hemagglutinin protein, modified by the removal of the polybasic cleavage peptide and (ii) the ectodomain of the NDV hemagglutinin-neuraminidase (HN) protein in the place of the ectodomain of influenza neuraminidase (Park MS, et al. Proc Natl Acad Sci USA 2006;103(21):8203-8). Here we show this virus is attenuated in primary normal human bronchial epithelial (NHBE) cell culture, and demonstrate protection of C57BL/6 mice from lethal challenge with an H5 HA-containing influenza virus through immunisation with the recombinant virus. In addition, in-ovo vaccination of 18-day-old embryonated chicken eggs provided 90% and 80% protection against highly stringent lethal challenge by NDV and H5N1 virus, respectively. We propose that this virus has potential as a safe in-ovo live, attenuated, bivalent avian influenza and Newcastle disease virus vaccine.

  20. Mouse Saliva Inhibits Transit of Influenza Virus to the Lower Respiratory Tract by Efficiently Blocking Influenza Virus Neuraminidase Activity.

    Science.gov (United States)

    Gilbertson, Brad; Ng, Wy Ching; Crawford, Simon; McKimm-Breschkin, Jenny L; Brown, Lorena E

    2017-07-15

    We previously identified a novel inhibitor of influenza virus in mouse saliva that halts the progression of susceptible viruses from the upper to the lower respiratory tract of mice in vivo and neutralizes viral infectivity in MDCK cells. Here, we investigated the viral target of the salivary inhibitor by using reverse genetics to create hybrid viruses with some surface proteins derived from an inhibitor-sensitive strain and others from an inhibitor-resistant strain. These viruses demonstrated that the origin of the viral neuraminidase (NA), but not the hemagglutinin or matrix protein, was the determinant of susceptibility to the inhibitor. Comparison of the NA sequences of a panel of H3N2 viruses with differing sensitivities to the salivary inhibitor revealed that surface residues 368 to 370 (N2 numbering) outside the active site played a key role in resistance. Resistant viruses contained an EDS motif at this location, and mutation to either EES or KDS, found in highly susceptible strains, significantly increased in vitro susceptibility to the inhibitor and reduced the ability of the virus to progress to the lungs when the viral inoculum was initially confined to the upper respiratory tract. In the presence of saliva, viral strains with a susceptible NA could not be efficiently released from the surfaces of infected MDCK cells and had reduced enzymatic activity based on their ability to cleave substrate in vitro This work indicates that the mouse has evolved an innate inhibitor similar in function, though not in mechanism, to what humans have created synthetically as an antiviral drug for influenza virus. IMPORTANCE Despite widespread use of experimental pulmonary infection of the laboratory mouse to study influenza virus infection and pathogenesis, to our knowledge, mice do not naturally succumb to influenza. Here, we show that mice produce their own natural form of neuraminidase inhibitor in saliva that stops the virus from reaching the lungs, providing a

  1. Isolation of a highly pathogenic influenza virus from turkeys.

    Science.gov (United States)

    McNulty, M S; Allan, G M; McCracken, R M; McParland, P J

    1985-01-01

    An influenza virus was isolated from turkeys with an acute disease causing 30% mortality. The virus was subtyped as H5 N8. The nomenclature A/turkey/Ireland/83 (H5 N8) is proposed for this isolate. The virus had an ICPI of 1.80 to 1.85 for 1-day-old chicks and an IVPI of 2.74 for 6-week-old chickens. Following oronasal inoculation of juvenile and adult turkeys, chickens and ducks with the isolate, 100% mortality occurred in turkeys and chickens. No clinical signs were observed in inoculated ducks, but all developed serum antibody titres against the virus.

  2. Technology transfer of oil-in-water emulsion adjuvant manufacturing for pandemic influenza vaccine production in Romania: Preclinical evaluation of split virion inactivated H5N1 vaccine with adjuvant.

    Science.gov (United States)

    Stavaru, Crina; Onu, Adrian; Lupulescu, Emilia; Tucureanu, Catalin; Rasid, Orhan; Vlase, Ene; Coman, Cristin; Caras, Iuliana; Ghiorghisor, Alina; Berbecila, Laurentiu; Tofan, Vlad; Bowen, Richard A; Marlenee, Nicole; Hartwig, Airn; Bielefeldt-Ohmann, Helle; Baldwin, Susan L; Van Hoeven, Neal; Vedvick, Thomas S; Huynh, Chuong; O'Hara, Michael K; Noah, Diana L; Fox, Christopher B

    2016-04-02

    Millions of seasonal and pandemic influenza vaccine doses containing oil-in-water emulsion adjuvant have been administered in order to enhance and broaden immune responses and to facilitate antigen sparing. Despite the enactment of a Global Action Plan for Influenza Vaccines and a multi-fold increase in production capabilities over the past 10 years, worldwide capacity for pandemic influenza vaccine production is still limited. In developing countries, where routine influenza vaccination is not fully established, additional measures are needed to ensure adequate supply of pandemic influenza vaccines without dependence on the shipment of aid from other, potentially impacted first-world countries. Adaptation of influenza vaccine and adjuvant technologies by developing country influenza vaccine manufacturers may enable antigen sparing and corresponding increases in global influenza vaccine coverage capacity. Following on previously described work involving the technology transfer of oil-in-water emulsion adjuvant manufacturing to a Romanian vaccine manufacturing institute, we herein describe the preclinical evaluation of inactivated split virion H5N1 influenza vaccine with emulsion adjuvant, including immunogenicity, protection from virus challenge, antigen sparing capacity, and safety. In parallel with the evaluation of the bioactivity of the tech-transferred adjuvant, we also describe the impact of concurrent antigen manufacturing optimization activities. Depending on the vaccine antigen source and manufacturing process, inclusion of adjuvant was shown to enhance and broaden functional antibody titers in mouse and rabbit models, promote protection from homologous virus challenge in ferrets, and facilitate antigen sparing. Besides scientific findings, the operational lessons learned are delineated in order to facilitate adaptation of adjuvant technologies by other developing country institutes to enhance global pandemic influenza preparedness.

  3. Predominance of influenza A(H1N1)pdm09 virus genetic subclade 6B.1 and influenza B/Victoria lineage viruses at the start of the 2015/16 influenza season in Europe

    DEFF Research Database (Denmark)

    Broberg, Eeva; Melidou, Angeliki; Prosenc, Katarina

    2016-01-01

    Influenza A(H1N1)pdm09 viruses predominated in the European influenza 2015/16 season. Most analysed viruses clustered in a new genetic subclade 6B.1, antigenically similar to the northern hemisphere vaccine component A/California/7/2009. The predominant influenza B lineage was Victoria compared...

  4. Perspective of Use of Antiviral Peptides against Influenza Virus

    Directory of Open Access Journals (Sweden)

    Sylvie Skalickova

    2015-10-01

    Full Text Available The threat of a worldwide influenza pandemic has greatly increased over the past decade with the emergence of highly virulent avian influenza strains. The increased frequency of drug-resistant influenza strains against currently available antiviral drugs requires urgent development of new strategies for antiviral therapy, too. The research in the field of therapeutic peptides began to develop extensively in the second half of the 20th century. Since then, the mechanisms of action for several peptides and their antiviral prospect received large attention due to the global threat posed by viruses. Here, we discussed the therapeutic properties of peptides used in influenza treatment. Peptides with antiviral activity against influenza can be divided into three main groups. First, entry blocker peptides such as a Flupep that interact with influenza hemagglutinin, block its binding to host cells and prevent viral fusion. Second, several peptides display virucidal activity, disrupting viral envelopes, e.g., Melittin. Finally, a third set of peptides interacts with the viral polymerase complex and act as viral replication inhibitors such as PB1 derived peptides. Here, we present a review of the current literature describing the antiviral activity, mechanism and future therapeutic potential of these influenza antiviral peptides.

  5. Influenza D Virus Infection in Feral Swine Populations, United States.

    Science.gov (United States)

    Ferguson, Lucas; Luo, Kaijian; Olivier, Alicia K; Cunningham, Fred L; Blackmon, Sherry; Hanson-Dorr, Katie; Sun, Hailiang; Baroch, John; Lutman, Mark W; Quade, Bianca; Epperson, William; Webby, Richard; DeLiberto, Thomas J; Wan, Xiu-Feng

    2018-06-01

    Influenza D virus (IDV) has been identified in domestic cattle, swine, camelid, and small ruminant populations across North America, Europe, Asia, South America, and Africa. Our study investigated seroprevalence and transmissibility of IDV in feral swine. During 2012-2013, we evaluated feral swine populations in 4 US states; of 256 swine tested, 57 (19.1%) were IDV seropositive. Among 96 archived influenza A virus-seropositive feral swine samples collected from 16 US states during 2010-2013, 41 (42.7%) were IDV seropositive. Infection studies demonstrated that IDV-inoculated feral swine shed virus 3-5 days postinoculation and seroconverted at 21 days postinoculation; 50% of in-contact naive feral swine shed virus, seroconverted, or both. Immunohistochemical staining showed viral antigen within epithelial cells of the respiratory tract, including trachea, soft palate, and lungs. Our findings suggest that feral swine might serve an important role in the ecology of IDV.

  6. Genetic diversity among pandemic 2009 influenza viruses isolated from a transmission chain

    DEFF Research Database (Denmark)

    Fordyce, Sarah Louise; Bragstad, Karoline; Pedersen, Svend Stenvang

    2013-01-01

    Influenza viruses such as swine-origin influenza A(H1N1) virus (A(H1N1)pdm09) generate genetic diversity due to the high error rate of their RNA polymerase, often resulting in mixed genotype populations (intra-host variants) within a single infection. This variation helps influenza to rapidly res...

  7. Cost-effectiveness of inactivated seasonal influenza vaccination in a cohort of Thai children ≤60 months of age.

    Science.gov (United States)

    Kittikraisak, Wanitchaya; Suntarattiwong, Piyarat; Ditsungnoen, Darunee; Pallas, Sarah E; Abimbola, Taiwo O; Klungthong, Chonticha; Fernandez, Stefan; Srisarang, Suchada; Chotpitayasunondh, Tawee; Dawood, Fatimah S; Olsen, Sonja J; Lindblade, Kim A

    2017-01-01

    Vaccination is the best measure to prevent influenza. We conducted a cost-effectiveness evaluation of trivalent inactivated seasonal influenza vaccination, compared to no vaccination, in children ≤60 months of age participating in a prospective cohort study in Bangkok, Thailand. A static decision tree model was constructed to simulate the population of children in the cohort. Proportions of children with laboratory-confirmed influenza were derived from children followed weekly. The societal perspective and one-year analytic horizon were used for each influenza season; the model was repeated for three influenza seasons (2012-2014). Direct and indirect costs associated with influenza illness were collected and summed. Cost of the trivalent inactivated seasonal influenza vaccine (IIV3) including promotion, administration, and supervision cost was added for children who were vaccinated. Quality-adjusted life years (QALY), derived from literature, were used to quantify health outcomes. The incremental cost-effectiveness ratio (ICER) was calculated as the difference in the expected total costs between the vaccinated and unvaccinated groups divided by the difference in QALYs for both groups. Compared to no vaccination, IIV3 vaccination among children ≤60 months in our cohort was not cost-effective in the introductory year (2012 season; 24,450 USD/QALY gained), highly cost-effective in the 2013 season (554 USD/QALY gained), and cost-effective in the 2014 season (16,200 USD/QALY gained). The cost-effectiveness of IIV3 vaccination among children participating in the cohort study varied by influenza season, with vaccine cost and proportion of high-risk children demonstrating the greatest influence in sensitivity analyses. Vaccinating children against influenza can be economically favorable depending on the maturity of the program, influenza vaccine performance, and target population.

  8. Cost-effectiveness of inactivated seasonal influenza vaccination in a cohort of Thai children ≤60 months of age.

    Directory of Open Access Journals (Sweden)

    Wanitchaya Kittikraisak

    Full Text Available Vaccination is the best measure to prevent influenza. We conducted a cost-effectiveness evaluation of trivalent inactivated seasonal influenza vaccination, compared to no vaccination, in children ≤60 months of age participating in a prospective cohort study in Bangkok, Thailand.A static decision tree model was constructed to simulate the population of children in the cohort. Proportions of children with laboratory-confirmed influenza were derived from children followed weekly. The societal perspective and one-year analytic horizon were used for each influenza season; the model was repeated for three influenza seasons (2012-2014. Direct and indirect costs associated with influenza illness were collected and summed. Cost of the trivalent inactivated seasonal influenza vaccine (IIV3 including promotion, administration, and supervision cost was added for children who were vaccinated. Quality-adjusted life years (QALY, derived from literature, were used to quantify health outcomes. The incremental cost-effectiveness ratio (ICER was calculated as the difference in the expected total costs between the vaccinated and unvaccinated groups divided by the difference in QALYs for both groups.Compared to no vaccination, IIV3 vaccination among children ≤60 months in our cohort was not cost-effective in the introductory year (2012 season; 24,450 USD/QALY gained, highly cost-effective in the 2013 season (554 USD/QALY gained, and cost-effective in the 2014 season (16,200 USD/QALY gained.The cost-effectiveness of IIV3 vaccination among children participating in the cohort study varied by influenza season, with vaccine cost and proportion of high-risk children demonstrating the greatest influence in sensitivity analyses. Vaccinating children against influenza can be economically favorable depending on the maturity of the program, influenza vaccine performance, and target population.

  9. Physician's knowledge, attitudes, and practices regarding seasonal influenza, pandemic influenza, and highly pathogenic avian influenza A (H5N1) virus infections of humans in Indonesia

    OpenAIRE

    Mangiri, Amalya; Iuliano, A. Danielle; Wahyuningrum, Yunita; Praptiningsih, Catharina Y.; Lafond, Kathryn E.; Storms, Aaron D.; Samaan, Gina; Ariawan, Iwan; Soeharno, Nugroho; Kreslake, Jennifer M.; Storey, J. Douglas; Uyeki, Timothy M.

    2016-01-01

    Indonesia has reported highest number of fatal human cases of highly pathogenic avian influenza (HPAI) A (H5N1) virus infection worldwide since 2005. There are limited data available on seasonal and pandemic influenza in Indonesia. During 2012, we conducted a survey of clinicians in two districts in western Java, Indonesia, to assess knowledge, attitudes, and practices (KAP) of clinical diagnosis, testing, and treatment of patients with seasonal influenza, pandemic influenza, or HPAI H5N1 vir...

  10. Effectiveness of seasonal trivalent inactivated influenza vaccine in preventing influenza hospitalisations and primary care visits in Auckland, New Zealand, in 2013.

    Science.gov (United States)

    Turner, N; Pierse, N; Bissielo, A; Huang, Qs; Radke, S; Baker, Mg; Widdowson, Ma; Kelly, H

    2014-08-28

    This study reports the first vaccine effectiveness (VE) estimates for the prevention of general practice visits and hospitalisations for laboratory-confirmed influenza from an urban population in Auckland, New Zealand, in the same influenza season (2013). A case test-negative design was used to estimate propensity-adjusted VE in both hospital and community settings. Patients with a severe acute respiratory infection (SARI) or influenza-like illness (ILI) were defined as requiring hospitalisation (SARI) or attending a general practice (ILI) with a history of fever or measured temperature ≥38 °C, cough and onset within the past 10 days. Those who tested positive for influenza virus were cases while those who tested negative were controls. Results were analysed to 7 days post symptom onset and adjusted for the propensity to be vaccinated and the timing during the influenza season. Influenza vaccination provided 52% (95% CI: 32 to 66) protection against laboratory-confirmed influenza hospitalisation and 56% (95% CI: 34 to 70) against presenting to general practice with influenza. VE estimates were similar for all types and subtypes. This study found moderate effectiveness of influenza vaccine against medically attended and hospitalised influenza in New Zealand, a temperate, southern hemisphere country during the 2013 winter season.

  11. Global surveillance of emerging Influenza virus genotypes by mass spectrometry.

    Directory of Open Access Journals (Sweden)

    Rangarajan Sampath

    2007-05-01

    Full Text Available Effective influenza surveillance requires new methods capable of rapid and inexpensive genomic analysis of evolving viral species for pandemic preparedness, to understand the evolution of circulating viral species, and for vaccine strain selection. We have developed one such approach based on previously described broad-range reverse transcription PCR/electrospray ionization mass spectrometry (RT-PCR/ESI-MS technology.Analysis of base compositions of RT-PCR amplicons from influenza core gene segments (PB1, PB2, PA, M, NS, NP are used to provide sub-species identification and infer influenza virus H and N subtypes. Using this approach, we detected and correctly identified 92 mammalian and avian influenza isolates, representing 30 different H and N types, including 29 avian H5N1 isolates. Further, direct analysis of 656 human clinical respiratory specimens collected over a seven-year period (1999-2006 showed correct identification of the viral species and subtypes with >97% sensitivity and specificity. Base composition derived clusters inferred from this analysis showed 100% concordance to previously established clades. Ongoing surveillance of samples from the recent influenza virus seasons (2005-2006 showed evidence for emergence and establishment of new genotypes of circulating H3N2 strains worldwide. Mixed viral quasispecies were found in approximately 1% of these recent samples providing a view into viral evolution.Thus, rapid RT-PCR/ESI-MS analysis can be used to simultaneously identify all species of influenza viruses with clade-level resolution, identify mixed viral populations and monitor global spread and emergence of novel viral genotypes. This high-throughput method promises to become an integral component of influenza surveillance.

  12. Serologic evidence of exposure of raptors to influenza A virus.

    Science.gov (United States)

    Redig, Patrick T; Goyal, Sagar M

    2012-06-01

    Serum or plasma samples from raptors that prey or scavenge upon aquatic birds were tested by a commercially available blocking enzyme-linked immunosorbent assay for the evidence of antibodies to influenza A virus. Samples were taken from birds (n = 616) admitted to two rehabilitation centers in the United States. In addition, samples from 472 migrating peregrine falcons (Falco peregrinus) trapped on autumnal and vernal migrations for banding purposes were also tested. Only bald eagles were notably seropositive (22/406). One each of peregrine falcon, great horned owl (Bubo virginianus), and Cooper's hawk (Accipiter cooperi) from a total of 472, 81, and 100, respectively, were also positive. None of the turkey vultures (n = 21) or black vultures (n = 8) was positive. No clinical signs referable to avian influenza were seen in any bird at the time of capture. These data indicate that, among raptors, bald eagles do have exposure to influenza A viruses.

  13. Surveillance of wild birds for avian influenza virus.

    Science.gov (United States)

    Hoye, Bethany J; Munster, Vincent J; Nishiura, Hiroshi; Klaassen, Marcel; Fouchier, Ron A M

    2010-12-01

    Recent demand for increased understanding of avian influenza virus in its natural hosts, together with the development of high-throughput diagnostics, has heralded a new era in wildlife disease surveillance. However, survey design, sampling, and interpretation in the context of host populations still present major challenges. We critically reviewed current surveillance to distill a series of considerations pertinent to avian influenza virus surveillance in wild birds, including consideration of what, when, where, and how many to sample in the context of survey objectives. Recognizing that wildlife disease surveillance is logistically and financially constrained, we discuss pragmatic alternatives for achieving probability-based sampling schemes that capture this host-pathogen system. We recommend hypothesis-driven surveillance through standardized, local surveys that are, in turn, strategically compiled over broad geographic areas. Rethinking the use of existing surveillance infrastructure can thereby greatly enhance our global understanding of avian influenza and other zoonotic diseases.

  14. Inactivation of RNA Viruses by Gamma Irradiation: A Study on Mitigating Factors

    Directory of Open Access Journals (Sweden)

    Adam J. Hume

    2016-07-01

    Full Text Available Effective inactivation of biosafety level 4 (BSL-4 pathogens is vital in order to study these agents safely. Gamma irradiation is a commonly used method for the inactivation of BSL-4 viruses, which among other advantages, facilitates the study of inactivated yet morphologically intact virions. The reported values for susceptibility of viruses to inactivation by gamma irradiation are sometimes inconsistent, likely due to differences in experimental protocols. We analyzed the effects of common sample attributes on the inactivation of a recombinant vesicular stomatitis virus expressing the Zaire ebolavirus glycoprotein and green fluorescent protein. Using this surrogate virus, we found that sample volume and protein content of the sample modulated viral inactivation by gamma irradiation but that air volume within the sample container and the addition of external disinfectant surrounding the sample did not. These data identify several factors which alter viral susceptibility to inactivation and highlight the usefulness of lower biosafety level surrogate viruses for such studies. Our results underscore the need to validate inactivation protocols of BSL-4 pathogens using “worst-case scenario” procedures to ensure complete sample inactivation.

  15. Chimeric Hemagglutinin Constructs Induce Broad Protection against Influenza B Virus Challenge in the Mouse Model

    OpenAIRE

    Ermler, Megan E.; Kirkpatrick, Ericka; Sun, Weina; Hai, Rong; Amanat, Fatima; Chromikova, Veronika; Palese, Peter; Krammer, Florian

    2017-01-01

    Seasonal influenza virus epidemics represent a significant public health burden. Approximately 25% of all influenza virus infections are caused by type B viruses, and these infections can be severe, especially in children. Current influenza virus vaccines are an effective prophylaxis against infection but are impacted by rapid antigenic drift, which can lead to mismatches between vaccine strains and circulating strains. Here, we describe a broadly protective vaccine candidate based on chimeri...

  16. Evaluation of sprayed hypochlorous acid solutions for their virucidal activity against avian influenza virus through in vitro experiments

    Science.gov (United States)

    HAKIM, Hakimullah; THAMMAKARN, Chanathip; SUGURO, Atsushi; ISHIDA, Yuki; KAWAMURA, Akinobu; TAMURA, Miho; SATOH, Keisuke; TSUJIMURA, Misato; HASEGAWA, Tomomi; TAKEHARA, Kazuaki

    2014-01-01

    Hypochlorous acid (HOCl) solutions were evaluated for their virucidal ability against a low pathogenic avian influenza virus (AIV), H7N1. HOCl solutions containing 50, 100 and 200 ppm chlorine (pH 6) or their sprayed solutions (harvested in dishes placed at 1 or 30 cm distance between the spray nozzle and dish) were mixed with the virus with or without organic materials (5% fetal bovine serum: FBS). Under plain diluent conditions (without FBS), harvested solutions of HOCl after spraying could decrease the AIV titer by more than 1,000 times, to an undetectable level (< 2.5 log10TCID50/ml) within 5 sec, with the exception of the 50 ppm solution harvested after spraying at the distance of 30 cm. Under the dirty conditions (in the presence of 5% FBS), they lost their virucidal activity. When HOCl solutions were sprayed directly on the virus on rayon sheets for 10 sec, the solutions of 100 and 200 ppm could inactivate AIV immediately after spraying, while 50 ppm solution required at least 3 min of contact time. In the indirect spray form, after 10 sec of spraying, the lids of the dishes were opened to expose the virus on rayon sheets to HOCl. In this form, the 200 ppm solution inactivated AIV within 10 min of contact, while 50 and 100 ppm could not inactivate it. These data suggest that HOCl can be used in spray form to inactivate AIV at the farm level. PMID:25421399

  17. Evaluation of sprayed hypochlorous acid solutions for their virucidal activity against avian influenza virus through in vitro experiments.

    Science.gov (United States)

    Hakim, Hakimullah; Thammakarn, Chanathip; Suguro, Atsushi; Ishida, Yuki; Kawamura, Akinobu; Tamura, Miho; Satoh, Keisuke; Tsujimura, Misato; Hasegawa, Tomomi; Takehara, Kazuaki

    2015-02-01

    Hypochlorous acid (HOCl) solutions were evaluated for their virucidal ability against a low pathogenic avian influenza virus (AIV), H7N1. HOCl solutions containing 50, 100 and 200 ppm chlorine (pH 6) or their sprayed solutions (harvested in dishes placed at 1 or 30 cm distance between the spray nozzle and dish) were mixed with the virus with or without organic materials (5% fetal bovine serum: FBS). Under plain diluent conditions (without FBS), harvested solutions of HOCl after spraying could decrease the AIV titer by more than 1,000 times, to an undetectable level (< 2.5 log10TCID50/ml) within 5 sec, with the exception of the 50 ppm solution harvested after spraying at the distance of 30 cm. Under the dirty conditions (in the presence of 5% FBS), they lost their virucidal activity. When HOCl solutions were sprayed directly on the virus on rayon sheets for 10 sec, the solutions of 100 and 200 ppm could inactivate AIV immediately after spraying, while 50 ppm solution required at least 3 min of contact time. In the indirect spray form, after 10 sec of spraying, the lids of the dishes were opened to expose the virus on rayon sheets to HOCl. In this form, the 200 ppm solution inactivated AIV within 10 min of contact, while 50 and 100 ppm could not inactivate it. These data suggest that HOCl can be used in spray form to inactivate AIV at the farm level.

  18. Perspective of Use of Antiviral Peptides against Influenza Virus

    Czech Academy of Sciences Publication Activity Database

    Skaličková, S.; Heger, Z.; Krejčová, L.; Pekárik, V.; Bastl, K.; Janda, Jozef; Kostolanský, F.; Varečková, E.; Zítka, O.; Adam, V.; Kizek, R.

    2015-01-01

    Roč. 7, č. 10 (2015), s. 5428-5442 ISSN 1999-4915 R&D Projects: GA MŠk ED2.1.00/03.0124 Institutional support: RVO:67985904 Keywords : cationic peptides * hemagglutinin * influenza virus Subject RIV: EE - Microbiology, Virology Impact factor: 3.042, year: 2015

  19. Protective Effect of Dietary Xylitol on Influenza A Virus Infection

    Science.gov (United States)

    Yin, Sun Young; Kim, Hyoung Jin; Kim, Hong-Jin

    2014-01-01

    Xylitol has been used as a substitute for sugar to prevent cavity-causing bacteria, and most studies have focused on its benefits in dental care. Meanwhile, the constituents of red ginseng (RG) are known to be effective in ameliorating the symptoms of influenza virus infection when they are administered orally for 14 days. In this study, we investigated the effect of dietary xylitol on influenza A virus infection (H1N1). We designed regimens containing various fractions of RG (RGs: whole extract, water soluble fraction, saponin and polysaccharide) and xylitol, and combination of xylitol with the RG fractions. Mice received the various combinations orally for 5 days prior to lethal influenza A virus infection. Almost all the mice died post challenge when xylitol or RGs were administered separately. Survival was markedly enhanced when xylitol was administered along with RGs, pointing to a synergistic effect. The effect of xylitol plus RG fractions increased with increasing dose of xylitol. Moreover, dietary xylitol along with the RG water soluble fraction significantly reduced lung virus titers after infection. Therefore, we suggest that dietary xylitol is effective in ameliorating influenza-induced symptoms when it is administered with RG fractions, and this protective effect of xylitol should be considered in relation to other diseases. PMID:24392148

  20. Protective effect of dietary xylitol on influenza A virus infection.

    Directory of Open Access Journals (Sweden)

    Sun Young Yin

    Full Text Available Xylitol has been used as a substitute for sugar to prevent cavity-causing bacteria, and most studies have focused on its benefits in dental care. Meanwhile, the constituents of red ginseng (RG are known to be effective in ameliorating the symptoms of influenza virus infection when they are administered orally for 14 days. In this study, we investigated the effect of dietary xylitol on influenza A virus infection (H1N1. We designed regimens containing various fractions of RG (RGs: whole extract, water soluble fraction, saponin and polysaccharide and xylitol, and combination of xylitol with the RG fractions. Mice received the various combinations orally for 5 days prior to lethal influenza A virus infection. Almost all the mice died post challenge when xylitol or RGs were administered separately. Survival was markedly enhanced when xylitol was administered along with RGs, pointing to a synergistic effect. The effect of xylitol plus RG fractions increased with increasing dose of xylitol. Moreover, dietary xylitol along with the RG water soluble fraction significantly reduced lung virus titers after infection. Therefore, we suggest that dietary xylitol is effective in ameliorating influenza-induced symptoms when it is administered with RG fractions, and this protective effect of xylitol should be considered in relation to other diseases.

  1. First characterization of avian influenza viruses from Greenland 2014

    DEFF Research Database (Denmark)

    Hartby, Christina Marie; Krog, Jesper Schak; Ravn Merkel, Flemming

    2016-01-01

    In late February 2014, unusually high numbers of wild birds, thick-billed murre (Uria lomvia), were found dead at the coast of South Greenland. To investigate the cause of death, 45 birds were submitted for laboratory examinations in Denmark. Avian influenza viruses (AIVs) with subtypes H11N2...

  2. The impact of the pandemic influenza A(H1N1) 2009 virus on seasonal influenza A viruses in the southern hemisphere, 2009.

    Science.gov (United States)

    Blyth, C C; Kelso, A; McPhie, K A; Ratnamohan, V M; Catton, M; Druce, J D; Smith, D W; Williams, S H; Huang, Q S; Lopez, L; Schoub, B D; Venter, M; Dwyer, D E

    2010-08-05

    Data collected over winter 2009 by five World Health Organisation National Influenza Centres in the southern hemisphere were used to examine the circulation of pandemic and seasonal influenza A strains during the first pandemic wave in the southern hemisphere.There is compelling evidence that the pandemic influenza A(H1N1) 2009 virus significantly displaced seasonal influenza A(H1N1) and, to a lesser extent, A(H3N2) viruses circulating in the southern hemisphere. Complete replacement of seasonal influenza A strains, however, was not observed during the first pandemic wave.

  3. Intranasal Immunization Using Mannatide as a Novel Adjuvant for an Inactivated Influenza Vaccine and Its Adjuvant Effect Compared with MF59.

    Directory of Open Access Journals (Sweden)

    Shu-Ting Ren

    Full Text Available Intranasal vaccination is more potent than parenteral injection for the prevention of influenza. However, because the poor efficiency of antigen uptake across the nasal mucosa is a key issue, immunostimulatory adjuvants are essential for intranasal vaccines. The immunomodulator mannatide or polyactin (PA has been used for the clinical treatment of impaired immunity in China, but its adjuvant effect on an inactivated trivalent influenza vaccine (ITIV via intranasal vaccination is unclear. To explore the adjuvant effect of PA, an inactivated trivalent influenza virus with or without PA or MF59 was instilled intranasally once a week in BALB/c mice. Humoral immunity was assessed by both the ELISA and hemagglutination inhibition (HI methods using antigen-specific antibodies. Splenic lymphocyte proliferation and the IFN-γ level were measured to evaluate cell-mediated immunity. The post-vaccination serum HI antibody geometric mean titers (GMTs for the H1N1 and H3N2 strains, antigen-specific serum IgG and IgA GMTs, mucosal SIgA GMT, splenic lymphocyte proliferation, and IFN-γ were significantly increased in the high-dose PA-adjuvanted vaccine group. The seroconversion rate and the mucosal response for the H3N2 strain were significantly elevated after high-dose PA administration. These adjuvant effects of high-dose PA for the influenza vaccine were comparable with those of the MF59 adjuvant, and abnormal signs or pathological changes were not found in the evaluated organs. In conclusion, PA is a novel mucosal adjuvant for intranasal vaccination with the ITIV that has safe and effective mucosal adjuvanticity in mice and successfully induces both serum and mucosal antibody responses and a cell-mediated response.

  4. Risk of Febrile Seizures and Epilepsy After Vaccination With Diphtheria, Tetanus, Acellular Pertussis, Inactivated Poliovirus, and Haemophilus Influenzae Type b

    DEFF Research Database (Denmark)

    Sun, Yuelian; Christensen, Jakob Christensen; Hviid, Anders

    2012-01-01

    -acellular pertussis–inactivated poliovirus– Haemophilus influenzae type b (DTaP-IPV-Hib) vaccine since September 2002. Objective To estimate the risk of febrile seizures and epilepsy after DTaP-IPV-Hib vaccination given at 3, 5, and 12 months. Design, Setting, and Participants A population-based cohort study of 378...

  5. Liposome-based cationic adjuvant CAF01 enhances the protection conferred by a commercial inactivated influenza vaccine in ferrets

    DEFF Research Database (Denmark)

    Martel, Cyril Jean-Marie; Agger, Else Marie; Jensen, Trine Hammer

    Objectives: To assess the effect of CAF01 adjuvant associated to a commercial trivalent inactivated influenza vaccine in the ferret model. Methods:  Ferrets were vaccinated with a range of doses of Sanofi-Pasteur's Vaxigrip with or without the CAF01 adjuvant, and challenged with either one of two H...

  6. Rapid Bedside Inactivation of Ebola Virus for Safe Nucleic Acid Tests

    DEFF Research Database (Denmark)

    Rosenstierne, Maiken Worsøe; Karlberg, Helen; Bragstad, Karoline

    2016-01-01

    Rapid bedside inactivation of Ebola virus would be a solution for the safety of medical and technical staff, risk containment, sample transport, and high-throughput or rapid diagnostic testing during an outbreak. We show that the commercially available Magna Pure lysis/binding buffer used...... for nucleic acid extraction inactivates Ebola virus. A rapid bedside inactivation method for nucleic acid tests is obtained by simply adding Magna Pure lysis/binding buffer directly into vacuum blood collection EDTA tubes using a thin needle and syringe prior to sampling. The ready-to-use inactivation vacuum...... tubes are stable for more than 4 months, and Ebola virus RNA is preserved in the Magna Pure lysis/binding buffer for at least 5 weeks independent of the storage temperature. We also show that Ebola virus RNA can be manually extracted from Magna Pure lysis/binding buffer-inactivated samples using...

  7. A Novel H1N2 Influenza Virus Related to the Classical and Human Influenza Viruses from Pigs in Southern China.

    Science.gov (United States)

    Song, Yafen; Wu, Xiaowei; Wang, Nianchen; Ouyang, Guowen; Qu, Nannan; Cui, Jin; Qi, Yan; Liao, Ming; Jiao, Peirong

    2016-01-01

    Southern China has long been considered to be an epicenter of pandemic influenza viruses. The special environment, breeding mode, and lifestyle in southern China provides more chances for wild aquatic birds, domestic poultry, pigs, and humans to be in contact. This creates the opportunity for interspecies transmission and generation of new influenza viruses. In this study, we reported a novel reassortant H1N2 influenza virus from pigs in southern China. According to the phylogenetic trees and homology of the nucleotide sequence, the virus was confirmed to be a novel triple-reassortant H1N2 virus containing genes from classical swine (PB2, PB1, HA, NP, and NS genes), triple-reassortant swine (PA and M genes), and recent human (NA gene) lineages. It indicated that the novel reassortment virus among human and swine influenza viruses occurred in pigs in southern China. The isolation of the novel reassortant H1N2 influenza viruses provides further evidence that pigs are "mixing vessels," and swine influenza virus surveillance in southern China will provide important information about genetic evaluation and antigenic variation of swine influenza virus to formulate the prevention and control measures for the viruses.

  8. Strategies for subtyping influenza viruses circulating in the Danish pig population

    DEFF Research Database (Denmark)

    Breum, Solvej Østergaard; Hjulsager, Charlotte Kristiane; Trebbien, Ramona

    2010-01-01

    in the Danish pig population functional and rapid subtyping assays are required. The conventional RT-PCR influenza subtyping assays developed by Chiapponi et al. (2003) have been implemented and used for typing of influenza viruses found positive in a pan influenza A real time RT-PCR assay. The H1 and N1 assays......Influenza viruses are endemic in the Danish pig population and the dominant circulating subtypes are H1N1, a Danish H1N2 reassortant, and H3N2. Here we present our current and future strategies for influenza virus subtyping. For diagnostic and surveillance of influenza subtypes circulating...... were specific when applied on Danish influenza positive samples, whereas the N2 assay consistently showed several unspecific PCR products. A subset of positive influenza samples detected by the real time RT-PCR screening assay could not be subtyped using these assays. Therefore, new influenza subtyping...

  9. Fatal case of influenza B virus pneumonia in a preterm neonate

    NARCIS (Netherlands)

    van den Dungen, F. A.; van Furth, A. M.; Fetter, W. P.; Zaaijer, H. L.; van Elburg, R. M.

    2001-01-01

    Influenza B infection typically has low mortality. A 1020-g neonate had a septic clinical picture and pneumonia. Influenza B virus was isolated from nasopharyngeal and tracheal aspirates. The infant died

  10. Unexpected Functional Divergence of Bat Influenza Virus NS1 Proteins.

    Science.gov (United States)

    Turkington, Hannah L; Juozapaitis, Mindaugas; Tsolakos, Nikos; Corrales-Aguilar, Eugenia; Schwemmle, Martin; Hale, Benjamin G

    2018-03-01

    Recently, two influenza A virus (FLUAV) genomes were identified in Central and South American bats. These sequences exhibit notable divergence from classical FLUAV counterparts, and functionally, bat FLUAV glycoproteins lack canonical receptor binding and destroying activity. Nevertheless, other features that distinguish these viruses from classical FLUAVs have yet to be explored. Here, we studied the viral nonstructural protein NS1, a virulence factor that modulates host signaling to promote efficient propagation. Like all FLUAV NS1 proteins, bat FLUAV NS1s bind double-stranded RNA and act as interferon antagonists. Unexpectedly, we found that bat FLUAV NS1s are unique in being unable to bind host p85β, a regulatory subunit of the cellular metabolism-regulating enzyme, phosphoinositide 3-kinase (PI3K). Furthermore, neither bat FLUAV NS1 alone nor infection with a chimeric bat FLUAV efficiently activates Akt, a PI3K effector. Structure-guided mutagenesis revealed that the bat FLUAV NS1-p85β interaction can be reengineered (in a strain-specific manner) by changing two to four NS1 residues (96L, 99M, 100I, and 145T), thereby creating a hydrophobic patch. Notably, ameliorated p85β-binding is insufficient for bat FLUAV NS1 to activate PI3K, and a chimeric bat FLUAV expressing NS1 with engineered hydrophobic patch mutations exhibits cell-type-dependent, but species-independent, propagation phenotypes. We hypothesize that bat FLUAV hijacking of PI3K in the natural bat host has been selected against, perhaps because genes in this metabolic pathway were differentially shaped by evolution to suit the unique energy use strategies of this flying mammal. These data expand our understanding of the enigmatic functional divergence between bat FLUAVs and classical mammalian and avian FLUAVs. IMPORTANCE The potential for novel influenza A viruses to establish infections in humans from animals is a source of continuous concern due to possible severe outbreaks or pandemics. The

  11. Molecular Epidemiology and Antigenic Characterization of Seasonal Influenza Viruses Circulating in Nepal.

    Science.gov (United States)

    Upadhyay, B P; Ghimire, P; Tashiro, M; Banjara, M R

    2017-01-01

    Influenza is one of the public health burdens in Nepal and its epidemiology is not clearly understood. The objective of this study was to explore the molecular epidemiology and the antigenic characteristics of the circulating influenza viruses in Nepal. A total of 1495 throat swab specimens were collected from January to December, 2014. Real time PCR assay was used for identification of influenza virus types and subtypes. Ten percent of the positive specimens were randomly selected and inoculated onto Madin-Darby Canine Kidney Epithelial cells (MDCK) for influenza virus isolation. All viruses were characterized by the hemagglutination inhibition (HI) assay. Influenza viruses were detected in 421/1495 (28.2%) specimens. Among positive cases, influenza A virus was detected in 301/421 (71.5%); of which 120 (39.9%) were influenza A/H1N1 pdm09 and 181 (60.1%) were influenza A/H3 subtype. Influenza B viruses were detected in 119/421 (28.3%) specimens. Influenza A/H1N1 pdm09, A/H3 and B viruses isolated in Nepal were antigenically similar to the vaccine strain influenza A/California/07/2009(H1N1pdm09), A/Texas/50/2012(H3N2), A/New York/39/2012(H3N2) and B/Massachusetts/2/2012, respectively. Influenza viruses were reported year-round in different geographical regions of Nepal which was similar to other tropical countries. The circulating influenza virus type and subtypes of Nepal were similar to vaccine candidate virus which could be prevented by currently used influenza vaccine.

  12. Effect of zymosan and poly (I:C) adjuvants on responses to microneedle immunization coated with whole inactivated influenza vaccine.

    Science.gov (United States)

    Shin, Ju-Hyung; Noh, Jin-Yong; Kim, Kwon-Ho; Park, Jae-Keun; Lee, Ji-Ho; Jeong, Seong Dong; Jung, Dae-Yoon; Song, Chang-Seon; Kim, Yeu-Chun

    2017-11-10

    Microneedles are the micrometer size devices used for the delivery of vaccines and biotherapeutics. In order to increase the vaccine efficacy and reduce the antigen dose, there is a significant need to find some adjuvants for the microneedle vaccination. In this study, zymosan, which is the cell wall preparation of Saccharomyces cerevisiae, or poly (I:C) was coated on a microneedle with inactivated influenza virus, and then immunized into BALB/c mouse to determine the immunogenicity, protection and synergetic effect between two adjuvants. As a result, the group administered with zymosan and vaccine antigen showed significantly stronger IgG response, HI titer and IgG subtypes without any adverse effects, compared to the group immunized with the vaccine antigen alone. Also, there were enhanced cellular immune responses in the group received adjuvant with vaccine antigen. In addition, they showed superior protection and lung viral reduction against lethal viral challenge. Taken together, this study confirms that zymosan can be used as an immunostimulant for microneedle vaccination. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Human influenza viruses and CD8(+) T cell responses.

    Science.gov (United States)

    Grant, Emma J; Quiñones-Parra, Sergio M; Clemens, E Bridie; Kedzierska, Katherine

    2016-02-01

    Influenza A viruses (IAVs) cause significant morbidity and mortality worldwide, despite new strain-specific vaccines being available annually. As IAV-specific CD8(+) T cells promote viral control in the absence of neutralizing antibodies, and can mediate cross-reactive immunity toward distinct IAVs to drive rapid recovery from both mild and severe influenza disease, there is great interest in developing a universal T cell vaccine. However, despite detailed studies in mouse models of influenza virus infection, there is still a paucity of data on human epitope-specific CD8(+) T cell responses to IAVs. This review focuses on our current understanding of human CD8(+) T cell immunity against distinct IAVs and discusses the possibility of achieving a CD8(+) T cell mediated-vaccine that protects against multiple, distinct IAV strains across diverse human populations. We also review the importance of CD8(+) T cell immunity in individuals highly susceptible to severe influenza infection, including those hospitalised with influenza, the elderly and Indigenous populations. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. A Promising IFN-Deficient System to Manufacture IFN-Sensitive Influenza Vaccine Virus.

    Science.gov (United States)

    Chen, Can; Fan, Wenhui; Li, Jing; Zheng, Weinan; Zhang, Shuang; Yang, Limin; Liu, Di; Liu, Wenjun; Sun, Lei

    2018-01-01

    Interferon (IFN)-sensitive and replication-incompetent influenza viruses are likely to be the alternatives to inactivated and attenuated virus vaccines. Some IFN-sensitive influenza vaccine candidates with modified non-structural protein 1 (NS1) are highly attenuated in IFN-competent hosts but induce robust antiviral immune responses. However, little research has been done on the manufacturability of these IFN-sensitive vaccine viruses. Here, RIG-I-knockout 293T cells were used to package the IFN-sensitive influenza A/WSN/33 (H1N1) virus expressing the mutant NS1 R38A/K41A. We found that the packaging efficiency of the NS1 R38A/K41A virus in RIG-I-knockout 293T cells was much higher than that in 293T cells. Moreover, the NS1 R38A/K41A virus almost lost its IFN antagonist activity and could no longer replicate in A549, MDCK, and Vero cells after 3-6 passages. This indicated that the replication of NS1 R38A/K41A virus is limited in conventional cells. Therefore, we further established a stable Vero cell line expressing the wild-type (WT) NS1 of the WSN virus, based on the Tet-On 3G system. The NS1 R38A/K41A virus was able to steadily propagate in this IFN-deficient cell line for at least 20 passages. In a mouse model, the NS1 R38A/K41A virus showed more than a 4-log reduction in lung virus titers compared to the WT virus at 3 and 5 days post infection. Furthermore, we observed that the NS1 R38A/K41A virus triggered high-level of IFN-α/β production in lung tissues and was eliminated from the host in a relatively short period of time. Additionally, this virus induced high-titer neutralizing antibodies against the WT WSN, A/Puerto Rico/8/1934 (PR8), or A/California/04/2009 (CA04) viruses and provided 100% protection against the WT WSN virus. Thus, we found that the replication of the NS1 R38A/K41A virus was limited in IFN-competent cells and mice. We also presented a promising IFN-deficient system, involving a RIG-I-knockout 293T cell line to package the IFN

  15. Influenza A Virus-Host Protein Interactions Control Viral Pathogenesis.

    Science.gov (United States)

    Zhao, Mengmeng; Wang, Lingyan; Li, Shitao

    2017-08-01

    The influenza A virus (IAV), a member of the Orthomyxoviridae family, is a highly transmissible respiratory pathogen and represents a continued threat to global health with considerable economic and social impact. IAV is a zoonotic virus that comprises a plethora of strains with different pathogenic profiles. The different outcomes of viral pathogenesis are dependent on the engagement between the virus and the host cellular protein interaction network. The interactions may facilitate virus hijacking of host molecular machinery to fulfill the viral life cycle or trigger host immune defense to eliminate the virus. In recent years, much effort has been made to discover the virus-host protein interactions and understand the underlying mechanisms. In this paper, we review the recent advances in our understanding of IAV-host interactions and how these interactions contribute to host defense and viral pathogenesis.

  16. Influenza and other respiratory viruses detected by influenza-like illness surveillance in Leyte Island, the Philippines, 2010-2013.

    Directory of Open Access Journals (Sweden)

    Hirono Otomaru

    Full Text Available This study aimed to determine the role of influenza-like illness (ILI surveillance conducted on Leyte Island, the Philippines, including involvement of other respiratory viruses, from 2010 to 2013. ILI surveillance was conducted from January 2010 to March 2013 with 3 sentinel sites located in Tacloban city, Palo and Tanauan of Leyte Island. ILI was defined as fever ≥38°C or feverish feeling and either cough or running nose in a patient of any age. Influenza virus and other 5 respiratory viruses were searched. A total of 5,550 ILI cases visited the 3 sites and specimens were collected from 2,031 (36.6% cases. Among the cases sampled, 1,637 (75.6% were children aged <5 years. 874 (43.0% cases were positive for at least one of the respiratory viruses tested. Influenza virus and respiratory syncytial virus (RSV were predominantly detected (both were 25.7% followed by human rhinovirus (HRV (17.5%. The age distributions were significantly different between those who were positive for influenza, HRV, and RSV. ILI cases were reported throughout the year and influenza virus was co-detected with those viruses on approximately half of the weeks of study period (RSV in 60.5% and HRV 47.4%. In terms of clinical manifestations, only the rates of headache and sore throat were significantly higher in influenza positive cases than cases positive to other viruses. In conclusion, syndromic ILI surveillance in this area is difficult to detect the start of influenza epidemic without laboratory confirmation which requires huge resources. Age was an important factor that affected positive rates of influenza and other respiratory viruses. Involvement of older age children may be useful to detect influenza more effectively.

  17. Replication of avian influenza A viruses in mammals.

    OpenAIRE

    Hinshaw, V S; Webster, R G; Easterday, B C; Bean, W J

    1981-01-01

    The recent appearance of an avian influenza A virus in seals suggests that viruses are transmitted from birds to mammals in nature. To examine this possibility, avian viruses of different antigenic subtypes were evaluated for their ability to replicate in three mammals-pigs, ferrets, and cats. In each of these mammals, avian strains replicated to high titers in the respiratory tract (10(5) to 10(7) 50% egg infective doses per ml of nasal wash), with peak titers at 2 to 4 days post-inoculation...

  18. Gnarled-trunk evolutionary model of influenza A virus hemagglutinin.

    Directory of Open Access Journals (Sweden)

    Kimihito Ito

    Full Text Available Human influenza A viruses undergo antigenic changes with gradual accumulation of amino acid substitutions on the hemagglutinin (HA molecule. A strong antigenic mismatch between vaccine and epidemic strains often requires the replacement of influenza vaccines worldwide. To establish a practical model enabling us to predict the future direction of the influenza virus evolution, relative distances of amino acid sequences among past epidemic strains were analyzed by multidimensional scaling (MDS. We found that human influenza viruses have evolved along a gnarled evolutionary pathway with an approximately constant curvature in the MDS-constructed 3D space. The gnarled pathway indicated that evolution on the trunk favored multiple substitutions at the same amino acid positions on HA. The constant curvature was reasonably explained by assuming that the rate of amino acid substitutions varied from one position to another according to a gamma distribution. Furthermore, we utilized the estimated parameters of the gamma distribution to predict the amino acid substitutions on HA in subsequent years. Retrospective prediction tests for 12 years from 1997 to 2009 showed that 70% of actual amino acid substitutions were correctly predicted, and that 45% of predicted amino acid substitutions have been actually observed. Although it remains unsolved how to predict the exact timing of antigenic changes, the present results suggest that our model may have the potential to recognize emerging epidemic strains.

  19. Universal antibodies against the highly conserved influenza fusion peptide cross-neutralize several subtypes of influenza A virus

    Energy Technology Data Exchange (ETDEWEB)

    Hashem, Anwar M. [Centre for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, HPFB, Health Canada, Ottawa, ON (Canada); Department of Microbiology, Faculty of Medicine, King Abdulaziz University, Jeddah (Saudi Arabia); Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON (Canada); Van Domselaar, Gary [National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB (Canada); Li, Changgui; Wang, Junzhi [National Institute for the Control of Pharmaceutical and Biological Products, Beijing (China); She, Yi-Min; Cyr, Terry D. [Centre for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, HPFB, Health Canada, Ottawa, ON (Canada); Sui, Jianhua [Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, 44 Binney Street, Boston, MA 02115 (United States); He, Runtao [National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB (Canada); Marasco, Wayne A. [Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, 44 Binney Street, Boston, MA 02115 (United States); Li, Xuguang, E-mail: Sean.Li@hc-sc.gc.ca [Centre for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, HPFB, Health Canada, Ottawa, ON (Canada); Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON (Canada)

    2010-12-10

    Research highlights: {yields} The fusion peptide is the only universally conserved epitope in all influenza viral hemagglutinins. {yields} Anti-fusion peptide antibodies are universal antibodies that cross-react with all influenza HA subtypes. {yields} The universal antibodies cross-neutralize different influenza A subtypes. {yields} The universal antibodies inhibit the fusion process between the viruses and the target cells. -- Abstract: The fusion peptide of influenza viral hemagglutinin plays a critical role in virus entry by facilitating membrane fusion between the virus and target cells. As the fusion peptide is the only universally conserved epitope in all influenza A and B viruses, it could be an attractive target for vaccine-induced immune responses. We previously reported that antibodies targeting the first 14 amino acids of the N-terminus of the fusion peptide could bind to virtually all influenza virus strains and quantify hemagglutinins in vaccines produced in embryonated eggs. Here we demonstrate that these universal antibodies bind to the viral hemagglutinins in native conformation presented in infected mammalian cell cultures and neutralize multiple subtypes of virus by inhibiting the pH-dependant fusion of viral and cellular membranes. These results suggest that this unique, highly-conserved linear sequence in viral hemagglutinin is exposed sufficiently to be attacked by the antibodies during the course of infection and merits further investigation because of potential importance in the protection against diverse strains of influenza viruses.

  20. Universal antibodies against the highly conserved influenza fusion peptide cross-neutralize several subtypes of influenza A virus

    International Nuclear Information System (INIS)

    Hashem, Anwar M.; Van Domselaar, Gary; Li, Changgui; Wang, Junzhi; She, Yi-Min; Cyr, Terry D.; Sui, Jianhua; He, Runtao; Marasco, Wayne A.; Li, Xuguang

    2010-01-01

    Research highlights: → The fusion peptide is the only universally conserved epitope in all influenza viral hemagglutinins. → Anti-fusion peptide antibodies are universal antibodies that cross-react with all influenza HA subtypes. → The universal antibodies cross-neutralize different influenza A subtypes. → The universal antibodies inhibit the fusion process between the viruses and the target cells. -- Abstract: The fusion peptide of influenza viral hemagglutinin plays a critical role in virus entry by facilitating membrane fusion between the virus and target cells. As the fusion peptide is the only universally conserved epitope in all influenza A and B viruses, it could be an attractive target for vaccine-induced immune responses. We previously reported that antibodies targeting the first 14 amino acids of the N-terminus of the fusion peptide could bind to virtually all influenza virus strains and quantify hemagglutinins in vaccines produced in embryonated eggs. Here we demonstrate that these universal antibodies bind to the viral hemagglutinins in native conformation presented in infected mammalian cell cultures and neutralize multiple subtypes of virus by inhibiting the pH-dependant fusion of viral and cellular membranes. These results suggest that this unique, highly-conserved linear sequence in viral hemagglutinin is exposed sufficiently to be attacked by the antibodies during the course of infection and merits further investigation because of potential importance in the protection against diverse strains of influenza viruses.

  1. Neuraminidase inhibitor susceptibility profile of human influenza viruses during the 2016-2017 influenza season in Mainland China.

    Science.gov (United States)

    Huang, Weijuan; Cheng, Yanhui; Li, Xiyan; Tan, Minju; Wei, Hejiang; Zhao, Xiang; Xiao, Ning; Dong, Jie; Wang, Dayan

    2018-06-01

    To understand the current situation of antiviral-resistance of influenza viruses to neuraminidase inhibitors (NAIs) in Mainland China, The antiviral-resistant surveillance data of the circulating influenza viruses in Mainland China during the 2016-2017 influenza season were analyzed. The total 3215 influenza viruses were studied to determine 50% inhibitory concentration (IC 50 ) for oseltamivir and zanamivir using a fluorescence-based assay. Approximately 0.3% (n = 10) of viruses showed either highly reduced inhibition (HRI) or reduced inhibition (RI) against at least one NAI. The most common neuraminidase (NA) amino acid substitution was H275Y in A (H1N1)pdm09 virus, which confers HRI by oseltamivir. Two A (H1N1)pdm09 viruses contained a new NA amino acid substitution respectively, S110F and D151E, which confers RI by oseltamivir or/and zanamivir. Two B/Victoria-lineage viruses harbored a new NA amino acid substitution respectively, H134Q and S246P, which confers RI by zanamivir. One B/Victoria-lineage virus contained dual amino acid substitution NA P124T and V422I, which confers HRI by zanamivir. One B/Yamagata-lineage virus was a reassortant virus that haemagglutinin (HA) from B/Yamagata-lineage virus and NA from B/Victoria-lineage virus, defined as B/Yamagata-lineage virus confers RI by oseltamivir, but as B/Victoria-lineage virus confers normal inhibition by oseltamivir. All new substitutions that have not been reported before, the correlation of these substitutions and observed changes in IC 50 should be further assessed. During the 2016-2017 influenza season in Mainland China the majority tested viruses were susceptible to oseltamivir and zanamivir. Hence, NAIs remain the recommended antiviral for treatment and prophylaxis of influenza virus infections. Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  2. Sparse evidence for equine or avian influenza virus infections among Mongolian adults with animal exposures.

    Science.gov (United States)

    Khurelbaatar, Nyamdavaa; Krueger, Whitney S; Heil, Gary L; Darmaa, Badarchiin; Ulziimaa, Daramragchaa; Tserennorov, Damdindorj; Baterdene, Ariungerel; Anderson, Benjamin D; Gray, Gregory C

    2013-11-01

    In recent years, Mongolia has experienced recurrent epizootics of equine influenza virus (EIV) among its 2·1 million horses and multiple incursions of highly pathogenic avian influenza (HPAI) virus via migrating birds. No human EIV or HPAI infections have been reported. In 2009, 439 adults in Mongolia were enrolled in a population-based study of zoonotic influenza transmission. Enrollment sera were examined for serological evidence of infection with nine avian, three human, and one equine influenza virus strains. Seroreactivity was sparse among participants suggesting little human risk of zoonotic influenza infection. © 2013 John Wiley & Sons Ltd.

  3. Genetic characterization of canine influenza A virus (H3N2) in Thailand.

    Science.gov (United States)

    Bunpapong, Napawan; Nonthabenjawan, Nutthawan; Chaiwong, Supassama; Tangwangvivat, Ratanaporn; Boonyapisitsopa, Supanat; Jairak, Waleemas; Tuanudom, Ranida; Prakairungnamthip, Duangduean; Suradhat, Sanipa; Thanawongnuwech, Roongroje; Amonsin, Alongkorn

    2014-02-01

    In January 2012, several clinical cases of dogs with flu-like symptoms, including coughing, sneezing, nasal discharge, and fever, were reported in a small-animal hospital located in Bangkok, Thailand. One influenza A virus was identified and characterized as an avian-like influenza virus H3N2. The virus was named A/canine/Thailand/CU-DC5299/12. A phylogenetic analysis indicated that the canine virus belonged to an avian Eurasian lineage and was genetically related to the canine influenza viruses H3N2 from China and Korea. This canine virus displays a unique genetic signature with two amino acid insertions in the NA protein, which is similar to the canine influenza viruses from eastern China (Zhejiang and Jiangsu). This study constitutes the first report of H3N2 canine influenza virus infection in a small-animal hospital in Thailand.

  4. No evidence that migratory geese disperse avian influenza viruses from breeding to wintering ground

    NARCIS (Netherlands)

    Yin, Shenglai; Kleijn, David; Müskens, Gerard J.D.M.; Fouchier, Ron A.M.; Verhagen, Josanne H.; Glazov, Petr M.; Si, Yali; Prins, Herbert H.T.; Boer, de Fred

    2017-01-01

    Low pathogenic avian influenza virus can mutate to a highly pathogenic strain that causes severe clinical signs in birds and humans. Migratory waterfowl, especially ducks, are considered the main hosts of low pathogenic avian influenza virus, but the role of geese in dispersing the virus over

  5. No evidence that migratory geese disperse avian influenza viruses from breeding to wintering ground

    NARCIS (Netherlands)

    Yin, S. (Shenglai); D. Kleijn (David); Müskens, G.J.D.M. (Gerard J. D. M.); R.A.M. Fouchier (Ron); J.H. Verhagen (Josanne); Glazov, P.M. (Petr M.); Si, Y. (Yali); Prins, H.H.T. (Herbert H. T.); De Boer, W.F. (Willem Frederik)

    2017-01-01

    textabstractLow pathogenic avian influenza virus can mutate to a highly pathogenic strain that causes severe clinical signs in birds and humans. Migratory waterfowl, especially ducks, are considered the main hosts of low pathogenic avian influenza virus, but the role of geese in dispersing the virus

  6. Molucular Epidemiology and Evolution of Influenza Viruses Circulating within European Swine between 2009 and 2013

    NARCIS (Netherlands)

    Watson, S.J.; Langat, P.; Reid, S.; Lam, T.; Cotten, M.; Kelly, M.; Reeth, Van K.; Qiu, Y.; Simon, G.; Bonin, E.; Foni, E.; Chiapponi, C.; Larsen, L.; Hjulsager, C.; Markowska-Daniel, I.; Urbaniak, K.; Durrwald, R.; Schlegel, M.; Huovilainen, A.; Davidson, I.; Dan, A.; Loeffen, W.L.A.; Edwards, S.; Bublot, M.; Vila, T.; Maldonado, J.; Valls, L.; Brown, I.H.; Pybus, O.G.; Kellam, P.

    2015-01-01

    The emergence in humans of the A(H1N1)pdm09 influenza virus, a complex reassortant virus of swine origin, highlighted the importance of worldwide influenza virus surveillance in swine. To date, large-scale surveillance studies have been reported for southern China and North America, but such data

  7. Adaptive pathways of zoonotic influenza viruses: from exposure to establishment in humans.

    Science.gov (United States)

    Reperant, Leslie A; Kuiken, Thijs; Osterhaus, Albert D M E

    2012-06-22

    Human influenza viruses have their ultimate origin in avian reservoirs and may adapt, either directly or after passage through another mammalian species, to circulate independently in the human population. Three sets of barriers must be crossed by a zoonotic influenza virus before it can become a human virus: animal-to-human transmission barriers; virus-cell interaction barriers; and human-to-human transmission barriers. Adaptive changes allowing zoonotic influenza viruses to cross these barriers have been studied extensively, generating key knowledge for improved pandemic preparedness. Most of these adaptive changes link acquired genetic alterations of the virus to specific adaptation mechanisms that can be screened for, both genetically and phenotypically, as part of zoonotic influenza virus surveillance programs. Human-to-human transmission barriers are only sporadically crossed by zoonotic influenza viruses, eventually triggering a worldwide influenza outbreak or pandemic. This is the most devastating consequence of influenza virus cross-species transmission. Progress has been made in identifying some of the determinants of influenza virus transmissibility. However, interdisciplinary research is needed to further characterize these ultimate barriers to the development of influenza pandemics, at both the level of the individual host and that of the population. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. The response of mute swans (Cygnus olor, Gm. 1789) to vaccination against avian influenza with an inactivated H5N2 vaccine.

    Science.gov (United States)

    Dolka, Beata; Żbikowski, Artur; Dolka, Izabella; Szeleszczuk, Piotr

    2016-10-22

    Recent epidemics of highly pathogenic avian influenza (HPAI) produced an unprecedented number of cases in mute swans (Cygnus olor) in European countries, which indicates that these birds are very sensitive to the H5N1 virus. The HPAI outbreaks stirred a debate on the controversial stamping-out policy in populations of protected bird species. After preventive vaccination had been approved in the European Union, several countries have introduced vaccination schemes to protect poultry, captive wild birds or exotic birds in zoos against HPAI. The aim of this study was to investigate the immune response of wild mute swans to immunization with an inactivated AI H5N2 vaccine approved for use in poultry. The serological responses of mute swans were assessed by comparison with racing pigeons (Columba livia), a species which is characterized by different susceptibility to infection with the H5N1 HPAI virus and plays a questionable role in the ecology of influenza (H5N1) viruses. Swans were vaccinated once or twice at an interval of 4 weeks. The humoral immune response was evaluated by hemagglutination inhibition (HI) and NP-ELISA. The lymphocyte blast transformation test was used to determine the cell-mediated immune response. Higher values of the geometric mean titer (GMT) and 100 % seroconversion (HI ≥32) were noted in double vaccinated swans (1448.2) than in single vaccinated swans (128.0) or in double vaccinated pigeons (215.3). Significant differences in HI titers were observed between swans and pigeons, but no variations in ELISA scores were noted after the booster dose. Immunization of swans had no effect on the proliferative activity of lymphocytes. The inactivated H5N2 vaccine was safe and immunogenic for mute swans and pigeons. Vaccination may have practical implications for swans kept in zoos, wildlife parks or rehabilitation centers. However, challenge studies are needed to prove the efficacy of the H5N2 AI vaccine.

  9. Cyclosporin A inhibits the propagation of influenza virus by interfering with a late event in the virus life cycle.

    Science.gov (United States)

    Hamamoto, Itsuki; Harazaki, Kazuhiro; Inase, Naohiko; Takaku, Hiroshi; Tashiro, Masato; Yamamoto, Norio

    2013-01-01

    Influenza is a global public health problem that causes a serious respiratory disease. Influenza virus frequently undergoes amino acid substitutions, which result in the emergence of drug-resistant viruses. To control influenza viruses that are resistant to currently available drugs, it is essential to develop new antiviral drugs with a novel molecular target. Here, we report that cyclosporin A (CsA) inhibits the propagation of influenza virus in A549 cells by interfering with a late event in the virus life cycle. CsA did not affect adsorption, internalization, viral RNA replication, or synthesis of viral proteins in A549 cells, but inhibited the step(s) after viral protein synthesis, such as assembly or budding. In addition, siRNA-mediated knockdown of the expression of the major CsA targets, namely cyclophilin A (CypA), cyclophilin B (CypB), and P-glycoprotein (Pgp), did not inhibit influenza virus propagation. These results suggest that CsA inhibits virus propagation by mechanism(s) independent of the inhibition of the function of CypA, CypB, and Pgp. CsA may target an unknown molecule that works as a positive regulator in the propagation of influenza virus. Our findings would contribute to the development of a novel anti-influenza virus therapy and clarification of the regulatory mechanism of influenza virus multiplication.

  10. Reduced incorporation of the influenza B virus BM2 protein in virus particles decreases infectivity

    International Nuclear Information System (INIS)

    Jackson, David; Zuercher, Thomas; Barclay, Wendy

    2004-01-01

    BM2 is the fourth integral membrane protein encoded by the influenza B virus genome. It is synthesized late in infection and transported to the plasma membrane from where it is subsequently incorporated into progeny virus particles. It has recently been reported that BM2 has ion channel activity and may be the functional homologue of the influenza A virus M2 protein acting as an ion channel involved in viral entry. Using a reverse genetic approach it was not possible to recover virus which lacked BM2. A recombinant influenza B virus was generated in which the BM2 AUG initiation codon was mutated to GUG. This decreased the efficiency of translation of BM2 protein such that progeny virions contained only 1/8 the amount of BM2 seen in wild-type virus. The reduction in BM2 incorporation resulted in a reduction in infectivity although there was no concomitant decrease in the numbers of virions released from the infected cells. These data imply that the incorporation of sufficient BM2 protein into influenza B virions is required for infectivity of the virus particles

  11. Influenza

    OpenAIRE

    Solórzano-Santos, Fortino; Miranda-Novales, Ma. Guadalupe

    2009-01-01

    La influenza es una infección viral aguda de las vías respiratorias, altamente contagiosa. Es causada por el virus de la influenza A, B y C. Puede afectar a todos los grupos etarios durante epidemias, aunque tiene mayor morbilidad en los extremos de la vida. La enfermedad frecuentemente requiere de atención médica y hospitalización, contribuyendo sustancialmente a pérdidas económicas, exceso en el número de días/cama-hospital y muertes. Considerando la epidemia reciente en México del virus de...

  12. Newcastle disease virus-based H5 influenza vaccine protects chickens from lethal challenge with a highly pathogenic H5N2 avian influenza virus

    OpenAIRE

    Ma, Jingjiao; Lee, Jinhwa; Liu, Haixia; Mena, Ignacio; Davis, A. Sally; Sunwoo, Sun Young; Lang, Yuekun; Duff, Michael; Morozov, Igor; Li, Yuhao; Yang, Jianmei; García-Sastre, Adolfo; Richt, Juergen A.; Ma, Wenjun

    2017-01-01

    Since December 2014, Eurasian-origin, highly pathogenic avian influenza H5 viruses including H5N1, H5N2, and H5N8 subtypes (called H5Nx viruses), which belong to the H5 clade 2.3.4.4, have been detected in U.S. wild birds. Subsequently, highly pathogenic H5N2 and H5N8 viruses have caused outbreaks in U.S. domestic poultry. Vaccination is one of the most effective ways to control influenza outbreaks and protect animal and public health. Newcastle disease virus (NDV)-based influenza vaccines ha...

  13. Differential lung NK cell responses in avian influenza virus infected chickens correlate with pathogenicity

    OpenAIRE

    Jansen, C.A.; de Geus, E.D.; van Haarlem, D.A.; van de Haar, P.M.; Löndt, B.Z; Graham, S.P.; Göbel, T.W.; van Eden, W.; Brookes, S.M.; Vervelde, L.

    2013-01-01

    Infection of chickens with low pathogenicity avian influenza (LPAI) virus results in mild clinical signs while infection with highly pathogenic avian influenza (HPAI) viruses causes death of the birds within 36–48 hours. Since natural killer (NK) cells have been shown to play an important role in influenza-specific immunity, we hypothesise that NK cells are involved in this difference in pathogenicity. To investigate this, the role of chicken NK-cells in LPAI virus infection was studied. Next...

  14. The assessment of efficacy of porcine reproductive respiratory syndrome virus inactivated vaccine based on the viral quantity and inactivation methods

    Directory of Open Access Journals (Sweden)

    Lee Byeongchun

    2011-06-01

    Full Text Available Abstract Background There have been many efforts to develop efficient vaccines for the control of porcine reproductive and respiratory syndrome virus (PRRSV. Although inactivated PRRSV vaccines are preferred for their safety, they are weak at inducing humoral immune responses and controlling field PRRSV infection, especially when heterologous viruses are involved. Results In all groups, the sample to positive (S/P ratio of IDEXX ELISA and the virus neutralization (VN titer remained negative until challenge. While viremia did not reduce in the vaccinated groups, the IDEXX-ELISA-specific immunoglobulin G increased more rapidly and to significantly greater levels 7 days after the challenge in all the vaccinated groups compared to the non-vaccinated groups (p 6 PFU/mL PRRSV vaccine-inoculated and binary ethylenimine (BEI-inactivated groups 22 days after challenge (p Conclusions The inactivated vaccine failed to show the humoral immunity, but it showed different immune response after the challenge compared to mock group. Although the 106 PFU/mL-vaccinated and BEI-inactivated groups showed significantly greater VN titers 22 days after challenge, all the groups were already negative for viremia.

  15. Detection of Evolutionarily Distinct Avian Influenza A Viruses in Antarctica

    Science.gov (United States)

    Vijaykrishna, Dhanasekaran; Butler, Jeffrey; Baas, Chantal; Maurer-Stroh, Sebastian; Silva-de-la-Fuente, M. Carolina; Medina-Vogel, Gonzalo; Olsen, Bjorn; Kelso, Anne; Barr, Ian G.; González-Acuña, Daniel

    2014-01-01

    ABSTRACT Distinct lineages of avian influenza viruses (AIVs) are harbored by spatially segregated birds, yet significant surveillance gaps exist around the globe. Virtually nothing is known from the Antarctic. Using virus culture, molecular analysis, full genome sequencing, and serology of samples from Adélie penguins in Antarctica, we confirmed infection by H11N2 subtype AIVs. Their genetic segments were distinct from all known contemporary influenza viruses, including South American AIVs, suggesting spatial separation from other lineages. Only in the matrix and polymerase acidic gene phylogenies did the Antarctic sequences form a sister relationship to South American AIVs, whereas distant phylogenetic relationships were evident in all other gene segments. Interestingly, their neuraminidase genes formed a distant relationship to all avian and human influenza lineages, and the polymerase basic 1 and polymerase acidic formed a sister relationship to the equine H3N8 influenza virus lineage that emerged during 1963 and whose avian origins were previously unknown. We also estimated that each gene segment had diverged for 49 to 80 years from its most closely related sequences, highlighting a significant gap in our AIV knowledge in the region. We also show that the receptor binding properties of the H11N2 viruses are predominantly avian and that they were unable to replicate efficiently in experimentally inoculated ferrets, suggesting their continuous evolution in avian hosts. These findings add substantially to our understanding of both the ecology and the intra- and intercontinental movement of Antarctic AIVs and highlight the potential risk of an incursion of highly pathogenic AIVs into this fragile environment. PMID:24803521

  16. Inactivation of 12 viruses by heating steps applied during manufacture of a hepatitis B vaccine

    NARCIS (Netherlands)

    Lelie, P. N.; Reesink, H. W.; Lucas, C. J.

    1987-01-01

    The efficacy of two heating cycles (90 sec at 103 degrees C and 10 hr at 65 degrees C) used during manufacture of a plasma-derived hepatitis-B vaccine was validated for the inactivation of 12 virus families. A period of 15 min warming up to 65 degrees C had already completely inactivated

  17. Influenza A viruses of avian origin circulating in pigs and other mammals.

    Science.gov (United States)

    Urbaniak, Kinga; Kowalczyk, Andrzej; Markowska-Daniel, Iwona

    2014-01-01

    Influenza A viruses (IAVs) are zoonotic agents, capable of crossing the species barriers. Nowadays, they still constitute a great challenge worldwide. The natural reservoir of all influenza A viruses are wild aquatic birds, despite the fact they have been isolated from a number of avian and mammalian species, including humans. Even when influenza A viruses are able to get into another than waterfowl population, they are often unable to efficiently adapt and transmit between individuals. Only in rare cases, these viruses are capable of establishing a new lineage. To succeed a complete adaptation and further transmission between species, influenza A virus must overcome a species barrier, including adaptation to the receptors of a new host, which would allow the virus-cell binding, virus replication and, then, animal-to-animal transmission. For many years, pigs were thought to be intermediate host for adaptation of avian influenza viruses to humans, because of their susceptibility to infection with both, avian and human influenza viruses, which supported hypothesis of pigs as a 'mixing vessel'. In this review, the molecular factors necessary for interspecies transmission are described, with special emphasis on adaptation of avian influenza viruses to the pig population. In addition, this review gives the information about swine influenza viruses circulating around the world with special emphasis on Polish strains.

  18. Vaccine-induced anti-HA2 antibodies promote virus fusion and enhance influenza virus respiratory disease.

    Science.gov (United States)

    Khurana, Surender; Loving, Crystal L; Manischewitz, Jody; King, Lisa R; Gauger, Phillip C; Henningson, Jamie; Vincent, Amy L; Golding, Hana

    2013-08-28

    Vaccine-induced disease enhancement has been described in connection with several viral vaccines in animal models and in humans. We investigated a swine model to evaluate mismatched influenza vaccine-associated enhanced respiratory disease (VAERD) after pH1N1 infection. Vaccinating pigs with whole inactivated H1N2 (human-like) virus vaccine (WIV-H1N2) resulted in enhanced pneumonia and disease after pH1N1 infection. WIV-H1N2 immune sera contained high titers of cross-reactive anti-pH1N1 hemagglutinin (HA) antibodies that bound exclusively to the HA2 domain but not to the HA1 globular head. No hemagglutination inhibition titers against pH1N1 (challenge virus) were measured. Epitope mapping using phage display library identified the immunodominant epitope recognized by WIV-H1N2 immune sera as amino acids 32 to 77 of pH1N1-HA2 domain, close to the fusion peptide. These cross-reactive anti-HA2 antibodies enhanced pH1N1 infection of Madin-Darby canine kidney cells by promoting virus membrane fusion activity. The enhanced fusion activity correlated with lung pathology in pigs. This study suggests a role for fusion-enhancing anti-HA2 antibodies in VAERD, in the absence of receptor-blocking virus-neutralizing antibodies. These findings should be considered during the evaluation of universal influenza vaccines designed to elicit HA2 stem-targeting antibodies.

  19. Occurrence of specific influenza antibodies in saliva and nasal secretion of monkeys (Macacus rhesus) after oral administration of influenza vaccine inactivated by gamma rays

    International Nuclear Information System (INIS)

    Tischner, H.; Huyuh, P.L.; Phan, P.N.; Bergmann, K.C.; Hoang, T.N.; Luther, P.; Nordheim, W.; Braeuniger, S.; Waldman, R.H.

    1984-01-01

    Antibodies in nasal secretion and saliva were measured in 10 Macacus rhesus wich had been immunized orally with a 60 Co-gamma-inactivated influenza vaccine. Prior to immunization monkeys had no detectable antibodies against hemagglutinin (HA) and neuraminidase, resp. in sera or secretions. Oral immunization using intraoesophageal tubing, induced the occurrence of both antiobodies in pilocarpine-stimulated secretions within 28 days but not in sera. 6 monkeys reacted with increasing HA antibodies in nasal secretions and 10 monkeys with increasing neuraminidase antibodies. Salivary HA antibodies occurred in 8 of 10 and neuraminidase antibodies in 9 of 10 animals. In most cases antibodies occurred in both secretions simultaneously. These results demonstrate the stimulation of antibodies specific to influenza in the respiratory tract of monkeys after oral immunization with an inactivated vaccine, for the first time. (author)

  20. Transmission of Avian Influenza Virus (H3N2) to Dogs

    OpenAIRE

    Song, Daesub; Kang, Bokyu; Lee, Chulseung; Jung, Kwonil; Ha, Gunwoo; Kang, Dongseok; Park, Seongjun; Park, Bongkyun; Oh, Jinsik

    2008-01-01

    In South Korea, where avian influenza virus subtypes H3N2, H5N1, H6N1, and H9N2 circulate or have been detected, 3 genetically similar canine influenza virus (H3N2) strains of avian origin (A/canine/Korea/01/2007, A/canine/Korea/02/2007, and A/canine/Korea/03/2007) were isolated from dogs exhibiting severe respiratory disease. To determine whether the novel canine influenza virus of avian origin was transmitted among dogs, we experimentally infected beagles with this influenza virus (H3N2) is...

  1. Systems Biology of Immune Response to Live and Inactivated Dengue Virus Vaccines

    Science.gov (United States)

    2017-09-01

    AWARD NUMBER: W81XWH-16-2-0032 TITLE: Systems Biology of Immune Response to Live and Inactivated Dengue Virus Vaccines PRINCIPAL INVESTIGATOR...CONTRACT NUMBER Systems Biology of Immune Response to Live and Inactivated Dengue Virus Vaccines 5b. GRANT NUMBER W81XWH-16-2-0032 5c. PROGRAM ELEMENT...cell) responses will be measured using molecular and cellular approaches and the data analyzed using a systems biology approach. During the first

  2. Systems Biology of the Immune Response to Live and Inactivated Dengue Virus Vaccines

    Science.gov (United States)

    2017-09-01

    AWARD NUMBER: W81XWH-16-2-0031 TITLE: Systems Biology of the Immune Response to Live and Inactivated Dengue Virus Vaccines PRINCIPAL...SUBTITLE 5a. CONTRACT NUMBER Systems Biology of the Immune Response to Live and Inactivated Dengue Virus Vaccines 5b. GRANT NUMBER W81XWH-16-2-0031 5c...adaptive (T and B cell) responses will be measured using molecular and cellular approaches and the data analyzed using a systems biology approach

  3. Rabies direct fluorescent antibody test does not inactivate rabies or eastern equine encephalitis viruses.

    Science.gov (United States)

    Jarvis, Jodie A; Franke, Mary A; Davis, April D

    2016-08-01

    An examination using the routine rabies direct fluorescent antibody test was performed on rabies or Eastern equine encephalitis positive mammalian brain tissue to assess inactivation of the virus. Neither virus was inactivated with acetone fixation nor the routine test, thus laboratory employees should treat all samples as rabies and when appropriate Eastern equine encephalitis positive throughout the whole procedure. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Unique Structural Features of Influenza Virus H15 Hemagglutinin

    Energy Technology Data Exchange (ETDEWEB)

    Tzarum, Netanel; McBride, Ryan; Nycholat, Corwin M.; Peng, Wenjie; Paulson, James C.; Wilson, Ian A. (Scripps)

    2017-04-12

    Influenza A H15 viruses are members of a subgroup (H7-H10-H15) of group 2 hemagglutinin (HA) subtypes that include H7N9 and H10N8 viruses that were isolated from humans during 2013. The isolation of avian H15 viruses is, however, quite rare and, until recently, geographically restricted to wild shorebirds and waterfowl in Australia. The HAs of H15 viruses contain an insertion in the 150-loop (loop beginning at position 150) of the receptor-binding site common to this subgroup and a unique insertion in the 260-loop compared to any other subtype. Here, we show that the H15 HA has a high preference for avian receptor analogs by glycan array analyses. The H15 HA crystal structure reveals that it is structurally closest to H7N9 HA, but the head domain of the H15 trimer is wider than all other HAs due to a tilt and opening of the HA1 subunits of the head domain. The extended 150-loop of the H15 HA retains the conserved conformation as in H7 and H10 HAs. Furthermore, the elongated 260-loop increases the exposed HA surface and can contribute to antigenic variation in H15 HAs. Since avian-origin H15 HA viruses have been shown to cause enhanced disease in mammalian models, further characterization and immune surveillance of H15 viruses are warranted.

    IMPORTANCEIn the last 2 decades, an apparent increase has been reported for cases of human infection by emerging avian influenza A virus subtypes, including H7N9 and H10N8 viruses isolated during 2013. H15 is the other member of the subgroup of influenza A virus group 2 hemagglutinins (HAs) that also include H7 and H10. H15 viruses have been restricted to Australia, but recent isolation of H15 viruses in western Siberia suggests that they could be spread more globally via the avian flyways that converge and emanate from this region. Here we report on characterization of the three-dimensional structure and receptor specificity of the H15 hemagglutinin, revealing distinct features and specificities that can

  5. Swine influenza virus vaccines: to change or not to change-that's the question.

    Science.gov (United States)

    Van Reeth, Kristien; Ma, Wenjun

    2013-01-01

    Commercial vaccines currently available against swine influenza virus (SIV) are inactivated, adjuvanted, whole virus vaccines, based on H1N1 and/or H3N2 and/or H1N2 SIVs. In keeping with the antigenic and genetic differences between SIVs circulating in Europe and the US, the vaccines for each region are produced locally and contain different strains. Even within a continent, there is no standardization of vaccine strains, and the antigen mass and adjuvants can also differ between different commercial products. Recombinant protein vaccines against SIV, vector, and DNA vaccines, and vaccines attenuated by reverse genetics have been tested in experimental studies, but they have not yet reached the market. In this review, we aim to present a critical analysis of the performance of commercial inactivated and novel generation SIV vaccines in experimental vaccination challenge studies in pigs. We pay special attention to the differences between commercial SIV vaccines and vaccination attitudes in Europe and in North America, to the issue of vaccine strain selection and changes, and to the potential advantages of novel generation vaccines over the traditional killed SIV vaccines.

  6. Development and Regulation of Novel Influenza Virus Vaccines: A United States Young Scientist Perspective.

    Science.gov (United States)

    Khurana, Surender

    2018-04-27

    Vaccination against influenza is the most effective approach for reducing influenza morbidity and mortality. However, influenza vaccines are unique among all licensed vaccines as they are updated and administered annually to antigenically match the vaccine strains and currently circulating influenza strains. Vaccine efficacy of each selected influenza virus vaccine varies depending on the antigenic match between circulating strains and vaccine strains, as well as the age and health status of the vaccine recipient. Low vaccine effectiveness of seasonal influenza vaccines in recent years provides an impetus to improve current seasonal influenza vaccines, and for development of next-generation influenza vaccines that can provide broader, long-lasting protection against both matching and antigenically diverse influenza strains. This review discusses a perspective on some of the issues and formidable challenges facing the development and regulation of the next-generation influenza vaccines.

  7. Oxygen-independent inactivation of Haemophilus influenzae transforming DNA by monochromatic radiation: action spectrum, effect of histidine and repair

    Energy Technology Data Exchange (ETDEWEB)

    Cabrera-Juarez, E; Setlow, J K; Swenson, P A; Peak, M J

    1976-01-01

    The action spectrum for the oxygen-independent inactivation of native transforming DNA from Haemophilus influenzae with near-uv radiation revealed a shoulder beginning at 334 and extending to 460 nm. The presence of 0.2 M histidine during irradiation produced a small increase in inactivation at 254, 290 and 313 nm, a large increase at 334 nm and a decrease in inactivation at 365, 405, and 460 nm. Photoreactivation did not reverse the DNA damage produced at pH 7.0 at 334, 365, 405 and 460 nm, but did reactivate the DNA after irradiation at 254, 290 and 313 nm. The inactivation of DNA irradiated at 254, 290 and 313 nm was considerably greater when the transforming ability was assayed in an excision-defective mutant compared with the wild type, although DNA irradiated at 334, 365, 405 and 460 nm showed smaller differences. These results suggest that the oxygen-independent inactivation of H. influenzae DNA at pH 7 by irradiation at 334, 365, 405 and 460 nm is caused by lesions other than pyrimidine dimers.

  8. Potential of acylated peptides to target the influenza A virus

    Directory of Open Access Journals (Sweden)

    Daniel Lauster

    2015-04-01

    Full Text Available For antiviral drug design, especially in the field of influenza virus research, potent multivalent inhibitors raise high expectations for combating epidemics and pandemics. Among a large variety of covalent and non-covalent scaffold systems for a multivalent display of inhibitors, we created a simple supramolecular platform to enhance the antiviral effect of our recently developed antiviral Peptide B (PeBGF, preventing binding of influenza virus to the host cell. By conjugating the peptide with stearic acid to create a higher-order structure with a multivalent display, we could significantly enhance the inhibitory effect against the serotypes of both human pathogenic influenza virus A/Aichi/2/1968 H3N2, and avian pathogenic A/FPV/Rostock/34 H7N1 in the hemagglutination inhibition assay. Further, the inhibitory potential of stearylated PeBGF (C18-PeBGF was investigated by infection inhibition assays, in which we achieved low micromolar inhibition constants against both viral strains. In addition, we compared C18-PeBGF to other published amphiphilic peptide inhibitors, such as the stearylated sugar receptor mimicking peptide (Matsubara et al. 2010, and the “Entry Blocker” (EB (Jones et al. 2006, with respect to their antiviral activity against infection by Influenza A Virus (IAV H3N2. However, while this strategy seems at a first glance promising, the native situation is quite different from our experimental model settings. First, we found a strong potential of those peptides to form large amyloid-like supramolecular assemblies. Second, in vivo, the large excess of cell surface membranes provides an unspecific target for the stearylated peptides. We show that acylated peptides insert into the lipid phase of such membranes. Eventually, our study reveals serious limitations of this type of self-assembling IAV inhibitors.

  9. Mechanism of aftered cytoskeleton organization in influenza virus infection

    International Nuclear Information System (INIS)

    Krizanova, O.; Ciampor, F.; Zavodska, E.; Matis, J.; Stancek, D.; Krivjanska, M.

    1989-01-01

    The autophosphorylation was followed of cytoskeleton (CS) isolated from control chick embryo cell membranes (CS-C) and from these membranes after influenza virus adsorption (CS-V) under conditions allowing to determine the activity of a single type proteinkinase. The Ca 2+ dependent calmodulin (CaM) kinase used different substrates from CS-V than did the c'AMP dependent proteinkinase. The catalytic subunit (c-subunit) of the c'AMP dependent proteinkinase added from outside phosphorylated the same polypeptides than the endogeneous c'AMP dependent proteinkinase, the further being more active than the latter. The purified influenza virus incorporated 32 P in the presence of the c-subunit only. Incubation of influenza virus with the c-subunit caused morphological changes visible by electron microscopy. The pleomorphy of the particles as well as their electron transmissibility were enhanced in the result of structural alterations and rarefaction of surface spikes of the haemagglutinin and neuraminidase. The contractibility of CS isolated from normal CEC and of the CS from CEC by 15 min postinfection (p.i.) was determined according to the actomyosin ATPase activity. The ATPase activity of the cytoskeleton in the presence of the Ca 2+ /CaM and that in the presence of c'AMP were used as controls. The virus as well as the Ca 2+ /CaM increased the ATPase activity. EGTA had no effect but did not interfere with virus stimulation, while c'AMP blocked the virus-induced enhancement of the ATPase activity. (author). 3 figs., 1 tab., 36 refs

  10. [Clinical aspects of human infection by the avian influenza virus].

    Science.gov (United States)

    Goubau, P

    2009-01-01

    The species barrier is not perfect for Influenza A and numerous transmissions of the virus from pigs or poultry to humans have been described these years. Appearing in 1997 and becoming epidemic in 2003, influenza A/H5N1 provoked many deadly enzootics in poultry batteries (highly pathogenic avian influenza of HPAI). Starting in Asia, many countries throughout Africa and Europe were affected. Sporadic human cases were described in direct contact with diseased chicken or other poultry. Half of the cases are lethal, but human to human transmission occurs with difficulty. From January 2003 to August 11th 2009, 438 cases were declared worldwide with 262 deaths. Many countries declared cases, but recently most cases occurred in Egypt. Measures in hospital were taken which were copied from the measures for SARS (Severe Acute Respiratory Syndrome), but these were probably excessive in this case, considering the low rate of secondary cases with A/H5N1. In many human infections, signs of severe respiratory distress develop and multi organ failure. It was feared that this deadly virus could become easily transmitted between humans, leading to a new pandemic. This was not the case up to now. The strong pathogenicity of the virus is still not completely explained, but the deep location of infection in the lungs and the deregulation of cytokine production by the target cells, particularly macrophages, may be part of the explanation.

  11. Antiviral activity of maca (Lepidium meyenii) against human influenza virus

    OpenAIRE

    Del Valle Mendoza, Juana; Pumarola, Tomas; Alzamora Gonzales, Libertad; Valle Mendoza, Luis Javier del

    2014-01-01

    Objective To investigate antiviral activity of maca to reduce viral load in Madin-Darby canine kidney (MDCK) cells infected with influenza type A and B viruses (Flu-A and Flu-B, respectively). Methods Maca were extracted with methanol (1:2, v/v). The cell viability and toxicity of the extracts were evaluated on MDCK cells using method MTT assay. Antiviral activity of compounds against Flu-A and Flu-B viruses was assayed using a test for determining the inhibition of the cytopathic ...

  12. DNA intercalator stimulates influenza transcription and virus replication

    Directory of Open Access Journals (Sweden)

    Poon Leo LM

    2011-03-01

    Full Text Available Abstract Influenza A virus uses its host transcription machinery to facilitate viral RNA synthesis, an event that is associated with cellular RNA polymerase II (RNAPII. In this study, various RNAPII transcription inhibitors were used to investigate the effect of RNAPII phosphorylation status on viral RNA transcription. A low concentration of DNA intercalators, such as actinomycin D (ActD, was found to stimulate viral polymerase activity and virus replication. This effect was not observed in cells treated with RNAPII kinase inhibitors. In addition, the loss of RNAPIIa in infected cells was due to the shift of nonphosphorylated RNAPII (RNAPIIa to hyperphosphorylated RNAPII (RNAPIIo.

  13. The use of FTA® filter papers for diagnosis of avian influenza virus.

    Science.gov (United States)

    Abdelwhab, E M; Lüschow, Dörte; Harder, Timm C; Hafez, Hafez M

    2011-06-01

    Avian influenza viruses (AIVs) infect a wide range of host species including domestic poultry and wild birds; also, AIVs may infect humans in whom some highly pathogenic viruses (HPAIV) may cause acute fatal disease. Accurate laboratory diagnosis of AIV infections requires time-consuming and logistically complex precautionary measures for shipment of specimens or viruses to avoid biohazard exposure. The feasibility was investigated of the Flinders Technology Associates filter paper (FTA® card) for infectivity of AIVs and to preserve viral RNA for detection by RT-qPCR, sequencing and by DNA microarray assay. The infectivity of AIV subtype H6N2 and HPAIV subtype H5N1 was inactivated completely within one hour after adsorption to the FTA card at room temperature. FTA-adsorbed viral RNA remained stable for five months. Swab samples obtained from chickens infected experimentally with H5N1 virus and spotted directly onto the FTA® cards allowed a sensitive and straightforward diagnosis by RT-qPCR. FTA® cards were also suitable for examination of field samples, although AIV RNA was detected with reduced sensitivity in comparison to direct examination of swab fluids. The use of FTA® cards will facilitate safe transport of samples for molecular diagnosis of AIV avoiding the need for an uninterrupted cold storage. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. Preparation of quadri-subtype influenza virus-like particles using bovine immunodeficiency virus gag protein

    Energy Technology Data Exchange (ETDEWEB)

    Tretyakova, Irina; Hidajat, Rachmat; Hamilton, Garrett; Horn, Noah; Nickols, Brian; Prather, Raphael O. [Medigen, Inc., 8420 Gas House Pike, Suite S, Frederick, MD (United States); Tumpey, Terrence M. [Influenza Division, Centers for Disease Control and Prevention, 1600 Clifton Road N.E., Atlanta, GA (United States); Pushko, Peter, E-mail: ppushko@medigen-usa.com [Medigen, Inc., 8420 Gas House Pike, Suite S, Frederick, MD (United States)

    2016-01-15

    Influenza VLPs comprised of hemagglutinin (HA), neuraminidase (NA), and matrix (M1) proteins have been previously used for immunological and virological studies. Here we demonstrated that influenza VLPs can be made in Sf9 cells by using the bovine immunodeficiency virus gag (Bgag) protein in place of M1. We showed that Bgag can be used to prepare VLPs for several influenza subtypes including H1N1 and H10N8. Furthermore, by using Bgag, we prepared quadri-subtype VLPs, which co-expressed within the VLP the four HA subtypes derived from avian-origin H5N1, H7N9, H9N2 and H10N8 viruses. VLPs showed hemagglutination and neuraminidase activities and reacted with specific antisera. The content and co-localization of each HA subtype within the quadri-subtype VLP were evaluated. Electron microscopy showed that Bgag-based VLPs resembled influenza virions with the diameter of 150–200 nm. This is the first report of quadri-subtype design for influenza VLP and the use of Bgag for influenza VLP preparation. - Highlights: • BIV gag protein was configured as influenza VLP core component. • Recombinant influenza VLPs were prepared in Sf9 cells using baculovirus expression system. • Single- and quadri-subtype VLPs were prepared by using BIV gag as a VLP core. • Co-localization of H5, H7, H9, and H10 HA was confirmed within quadri-subtype VLP. • Content of HA subtypes within quadri-subtype VLP was determined. • Potential advantages of quadri-subtype VLPs as influenza vaccine are discussed.

  15. Preparation of quadri-subtype influenza virus-like particles using bovine immunodeficiency virus gag protein

    International Nuclear Information System (INIS)

    Tretyakova, Irina; Hidajat, Rachmat; Hamilton, Garrett; Horn, Noah; Nickols, Brian; Prather, Raphael O.; Tumpey, Terrence M.; Pushko, Peter

    2016-01-01

    Influenza VLPs comprised of hemagglutinin (HA), neuraminidase (NA), and matrix (M1) proteins have been previously used for immunological and virological studies. Here we demonstrated that influenza VLPs can be made in Sf9 cells by using the bovine immunodeficiency virus gag (Bgag) protein in place of M1. We showed that Bgag can be used to prepare VLPs for several influenza subtypes including H1N1 and H10N8. Furthermore, by using Bgag, we prepared quadri-subtype VLPs, which co-expressed within the VLP the four HA subtypes derived from avian-origin H5N1, H7N9, H9N2 and H10N8 viruses. VLPs showed hemagglutination and neuraminidase activities and reacted with specific antisera. The content and co-localization of each HA subtype within the quadri-subtype VLP were evaluated. Electron microscopy showed that Bgag-based VLPs resembled influenza virions with the diameter of 150–200 nm. This is the first report of quadri-subtype design for influenza VLP and the use of Bgag for influenza VLP preparation. - Highlights: • BIV gag protein was configured as influenza VLP core component. • Recombinant influenza VLPs were prepared in Sf9 cells using baculovirus expression system. • Single- and quadri-subtype VLPs were prepared by using BIV gag as a VLP core. • Co-localization of H5, H7, H9, and H10 HA was confirmed within quadri-subtype VLP. • Content of HA subtypes within quadri-subtype VLP was determined. • Potential advantages of quadri-subtype VLPs as influenza vaccine are discussed.

  16. A quantitative comet infection assay for influenza virus

    Science.gov (United States)

    Lindsay, Stephen M.; Timm, Andrea; Yin, John

    2011-01-01

    Summary The virus comet assay is a cell-based virulence assay used to evaluate an antiviral drug or antibody against a target virus. The comet assay differs from the plaque assay in allowing spontaneous flows in 6-well plates to spread virus. When implemented quantitatively the comet assay has been shown to have an order-of-magnitude greater sensitivity to antivirals than the plaque assay. In this study, a quantitative comet assay for influenza virus is demonstrated, and is shown to have a 13-fold increase in sensitivity to ribavirin. AX4 cells (MDCK cells with increased surface concentration of α2–6 sialic acid, the influenza virus receptor) have reduced the comet size variability relative to MDCK cells, making them a better host cell for use in this assay. Because of enhanced antiviral sensitivity in flow-based assays, less drug is required, which could lead to lower reagent costs, reduced cytotoxicity, and fewer false-negative drug screen results. The comet assay also serves as a readout of flow conditions in the well. Observations from comets formed at varying humidity levels indicate a role for evaporation in the mechanism of spontaneous fluid flow in wells. PMID:22155578

  17. Reduction of influenza virus titer and protection against influenza virus infection in infant mice fed Lactobacillus casei Shirota.

    Science.gov (United States)

    Yasui, Hisako; Kiyoshima, Junko; Hori, Tetsuji

    2004-07-01

    We investigated whether oral administration of Lactobacillus casei strain Shirota to neonatal and infant mice ameliorates influenza virus (IFV) infection in the upper respiratory tract and protects against influenza infection. In a model of upper respiratory IFV infection, the titer of virus in the nasal washings of infant mice administered L. casei Shirota (L. casei Shirota group) was significantly (P survival rate of the L. casei Shirota group was significantly (P L. casei Shirota group were significantly greater than those of mice in the control group. These findings suggest that oral administration of L. casei Shirota activates the immature immune system of neonatal and infant mice and protects against IFV infection. Therefore, oral administration of L. casei Shirota may accelerate the innate immune response of the respiratory tract and protect against various respiratory infections in neonates, infants, and children, a high risk group for viral and bacterial infections.

  18. Influenza in migratory birds and evidence of limited intercontinental virus exchange.

    Directory of Open Access Journals (Sweden)

    Scott Krauss

    2007-11-01

    Full Text Available Migratory waterfowl of the world are the natural reservoirs of influenza viruses of all known subtypes. However, it is unknown whether these waterfowl perpetuate highly pathogenic (HP H5 and H7 avian influenza viruses. Here we report influenza virus surveillance from 2001 to 2006 in wild ducks in Alberta, Canada, and in shorebirds and gulls at Delaware Bay (New Jersey, United States, and examine the frequency of exchange of influenza viruses between the Eurasian and American virus clades, or superfamilies. Influenza viruses belonging to each of the subtypes H1 through H13 and N1 through N9 were detected in these waterfowl, but H14 and H15 were not found. Viruses of the HP Asian H5N1 subtypes were not detected, and serologic studies in adult mallard ducks provided no evidence of their circulation. The recently described H16 subtype of influenza viruses was detected in American shorebirds and gulls but not in ducks. We also found an unusual cluster of H7N3 influenza viruses in shorebirds and gulls that was able to replicate well in chickens and kill chicken embryos. Genetic analysis of 6,767 avian influenza gene segments and 248 complete avian influenza viruses supported the notion that the exchange of entire influenza viruses between the Eurasian and American clades does not occur frequently. Overall, the available evidence does not support the perpetuation of HP H5N1 influenza in migratory birds and suggests that the introduction of HP Asian H5N1 to the Americas by migratory birds is likely to be a rare event.

  19. Ebola Virus and Marburg Virus in Human Milk Are Inactivated by Holder Pasteurization.

    Science.gov (United States)

    Hamilton Spence, Erin; Huff, Monica; Shattuck, Karen; Vickers, Amy; Yun, Nadezda; Paessler, Slobodan

    2017-05-01

    Potential donors of human milk are screened for Ebola virus (EBOV) using standard questions, but testing for EBOV and Marburg virus (MARV) is not part of routine serological testing performed by milk banks. Research aim: This study tested the hypothesis that EBOV would be inactivated in donor human milk (DHM) by standard pasteurization techniques (Holder) used in all North American nonprofit milk banks. Milk samples were obtained from a nonprofit milk bank. They were inoculated with EBOV (Zaire strain) and MARV (Angola strain) and processed by standard Holder pasteurization technique. Plaque assays for EBOV and MARV were performed to detect the presence of virus after pasteurization. Neither EBOV nor MARV was detectable by viral plaque assay in DHM or culture media samples, which were pasteurized by the Holder process. EBOV and MARV are safely inactivated in human milk by standard Holder pasteurization technique. Screening for EBOV or MARV beyond questionnaire and self-deferral is not needed to ensure safety of DHM for high-risk infants.

  20. Influenza A virus targets a cGAS-independent STING pathway that controls enveloped RNA viruses.

    Science.gov (United States)

    Holm, Christian K; Rahbek, Stine H; Gad, Hans Henrik; Bak, Rasmus O; Jakobsen, Martin R; Jiang, Zhaozaho; Hansen, Anne Louise; Jensen, Simon K; Sun, Chenglong; Thomsen, Martin K; Laustsen, Anders; Nielsen, Camilla G; Severinsen, Kasper; Xiong, Yingluo; Burdette, Dara L; Hornung, Veit; Lebbink, Robert Jan; Duch, Mogens; Fitzgerald, Katherine A; Bahrami, Shervin; Mikkelsen, Jakob Giehm; Hartmann, Rune; Paludan, Søren R

    2016-02-19

    Stimulator of interferon genes (STING) is known be involved in control of DNA viruses but has an unexplored role in control of RNA viruses. During infection with DNA viruses STING is activated downstream of cGAMP synthase (cGAS) to induce type I interferon. Here we identify a STING-dependent, cGAS-independent pathway important for full interferon production and antiviral control of enveloped RNA viruses, including influenza A virus (IAV). Further, IAV interacts with STING through its conserved hemagglutinin fusion peptide (FP). Interestingly, FP antagonizes interferon production induced by membrane fusion or IAV but not by cGAMP or DNA. Similar to the enveloped RNA viruses, membrane fusion stimulates interferon production in a STING-dependent but cGAS-independent manner. Abolishment of this pathway led to reduced interferon production and impaired control of enveloped RNA viruses. Thus, enveloped RNA viruses stimulate a cGAS-independent STING pathway, which is targeted by IAV.

  1. Efficacy of two H5N9-inactivated vaccines against challenge with a recent H5N1 highly pathogenic avian influenza isolate from a chicken in Thailand.

    Science.gov (United States)

    Bublot, Michel; Le Gros, François-Xavier; Nieddu, Daniela; Pritchard, Nikki; Mickle, Thomas R; Swayne, David E

    2007-03-01

    The objective of this study was to compare the efficacy of two avian influenza (AI) H5-inactivated vaccines containing either an American (A/turkey/Wisconsin/68 H5N9; H5N9-WI) or a Eurasian isolate (A/chicken/Italy/22A/98 H5N9; H5N9-It). Three-week-old specific pathogen-free chickens were vaccinated once and challenged 3 wk later with a H5N1 highly pathogenic AI (HPAI) virus isolated from a chicken in Thailand in 2004. All unvaccinated challenged birds died within 2 days, whereas 90% and 100% of chickens vaccinated with H5N9-WI and H5N9-It, respectively, were protected against morbidity and mortality. Both vaccines prevented cloacal shedding and significantly reduced oral shedding of the challenge HPAI virus. Additional chickens (vaccinated or unvaccinated) were placed in contact with the directly challenged birds 18 hr after challenge. All unvaccinated chickens in contact with unvaccinated challenged birds died within 3 days after contact, whereas unvaccinated chickens in contact with vaccinated challenged birds either showed a significantly delayed mortality or did not become infected. All vaccinated contacts were protected against clinical signs, and most chickens did not shed detectable amount of HPAI virus. Altogether, these data indicate that both vaccines protected very well against morbidity and mortality and reduced or prevented shedding induced by direct or contact exposure to Asian H5N1 HPAI virus.

  2. Matrix protein 2 of influenza A virus blocks autophagosome fusion with lysosomes

    DEFF Research Database (Denmark)

    Gannagé, Monique; Dormann, Dorothee; Albrecht, Randy

    2009-01-01

    Influenza A virus is an important human pathogen causing significant morbidity and mortality every year and threatening the human population with epidemics and pandemics. Therefore, it is important to understand the biology of this virus to develop strategies to control its pathogenicity. Here, we...... demonstrate that influenza A virus inhibits macroautophagy, a cellular process known to be manipulated by diverse pathogens. Influenza A virus infection causes accumulation of autophagosomes by blocking their fusion with lysosomes, and one viral protein, matrix protein 2, is necessary and sufficient...... for this inhibition of autophagosome degradation. Macroautophagy inhibition by matrix protein 2 compromises survival of influenza virus-infected cells but does not influence viral replication. We propose that influenza A virus, which also encodes proapoptotic proteins, is able to determine the death of its host cell...

  3. Household-based costs and benefits of vaccinating healthy children in daycare against influenza virus: results from a pilot study.

    Science.gov (United States)

    Pisu, Maria; Meltzer, Martin I; Hurwitz, Eugene S; Haber, Michael

    2005-01-01

    Vaccinating children against influenza virus may reduce infections in immunised children and household contacts, thereby reducing the household-based cost associated with respiratory illnesses. To evaluate the impact of influenza virus vaccination of daycare children on costs of respiratory illnesses of the children and their household contacts from the household and societal perspective. Cost analysis of data from a randomised controlled trial covering the period November to April of 1996-7 and 1998-9. Children (127 in 1996-7 and 133 in 1998-9) from daycare centres in Californian (USA) naval bases received influenza virus vaccine (inactivated) or hepatitis A virus vaccination. Direct and indirect costs (1997 and 1999 US dollars) of respiratory illnesses in households of vaccinated and not vaccinated daycare children, excluding the cost of vaccination. There were no statistically significant differences in household costs of respiratory illness between households with or without influenza virus-vaccinated children (USD 635 vs USD 492: p = 0.98 [1996-7]; USD 412.70 vs USD 499.50: p = 0.42 [1998-9]). In 1996-7, adult and 5- to 17-year-old contacts of vaccinated children had lower household costs than contacts of unvaccinated children (USD 58.50 vs USD 83.20, p = 0.01 and USD 32.80 vs USD 59.50, p = 0.04, respectively), while vaccinated children 0-4 years old had higher household costs than unvaccinated children in the same age group (USD 383 vs USD 236, p = 0.05). In 1998-9, there were no differences within individual age groups. Results from societal perspective were similar. Overall, from both the household and societal perspectives, there were no economic benefits to households from vaccinating daycare children against influenza virus. However, we found some over-time inconsistency in results; this should be considered if changing recommendations about routine influenza virus vaccination of healthy children. Our study size may limit the generalisability of the

  4. [Molecular analyses of human influenza viruses. Circulation of new variants since 1995/96].

    Science.gov (United States)

    Biere, B; Schweiger, B

    2008-09-01

    The evolution of influenza viruses is increasingly pursued by molecular analyses that complement classical methods. The analyses focus on the two surface proteins hemagglutinin (HA) and neuraminidase (NA) which determine the viral antigenic profile. Influenza A(H3N2) viruses are exceptionally variable, so that usually at least two virus variants cocirculate at the same time. Together with influenza B viruses they caused approximately 90% of influenza virus infections in Germany during the last 12 seasons, while influenza A(H1N1) viruses only played a subordinate part. Unexpectedly, reassorted viruses of subtype A(H1N2) appeared during the seasons 2001/02 and 2002/03, but were isolated only rarely and gained no epidemiological significance. Furthermore, during the season 2001/02 influenza B viruses of the Victoria-lineage reappeared in Germany and other countries of the northern hemisphere after 10 years of absence. These viruses reassorted with the cocirculating Yamagata-like influenza B viruses, as could be seen by the appearance of viruses with a Victoria-like HA and a Yamagata-like NA.

  5. Novel reassortant of swine influenza H1N2 virus in Germany.

    Science.gov (United States)

    Zell, Roland; Motzke, Susann; Krumbholz, Andi; Wutzler, Peter; Herwig, Volker; Dürrwald, Ralf

    2008-01-01

    European porcine H1N2 influenza viruses arose after multiple reassortment steps involving a porcine influenza virus with avian-influenza-like internal segments and human H1N1 and H3N2 viruses in 1994. In Germany, H1N2 swine influenza viruses first appeared in 2000. Two German H1N2 swine influenza virus strains isolated from pigs with clinical symptoms of influenza are described. They were characterized by the neutralization test, haemagglutination inhibition (HI) test and complete sequencing of the viral genomes. The data demonstrate that these viruses represent a novel H1N2 reassortant. The viruses showed limited neutralization by sera raised against heterologous A/sw/Bakum/1,832/00-like H1N2 viruses. Sera pools from recovered pigs showed a considerably lower HI reaction, indicative of diagnostic difficulties in using the HI test to detect these viruses with A/sw/Bakum/1,832/00-like H1N2 antigens. Genome sequencing revealed the novel combination of the human-like HAH1 gene of European porcine H1N2 influenza viruses and the NAN2 gene of European porcine H3N2 viruses.

  6. 21 CFR 866.3332 - Reagents for detection of specific novel influenza A viruses.

    Science.gov (United States)

    2010-04-01

    ... HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological... novel influenza A viruses in patients with clinical risk of infection with these viruses, and also aids...

  7. Contemporary Avian Influenza A Virus Subtype H1, H6, H7, H10, and H15 Hemagglutinin Genes Encode a Mammalian Virulence Factor Similar to the 1918 Pandemic Virus H1 Hemagglutinin

    OpenAIRE

    Qi, Li; Pujanauski, Lindsey M.; Davis, A. Sally; Schwartzman, Louis M.; Chertow, Daniel S.; Baxter, David; Scherler, Kelsey; Hartshorn, Kevan L.; Slemons, Richard D.; Walters, Kathie-Anne; Kash, John C.; Taubenberger, Jeffery K.

    2014-01-01

    ABSTRACT Zoonotic avian influenza virus infections may lead to epidemics or pandemics. The 1918 pandemic influenza virus has an avian influenza virus-like genome, and its H1 hemagglutinin was identified as a key mammalian virulence factor. A chimeric 1918 virus expressing a contemporary avian H1 hemagglutinin, however, displayed murine pathogenicity indistinguishable from that of the 1918 virus. Here, isogenic chimeric avian influenza viruses were constructed on an avian influenza virus backb...

  8. Molecular Epidemiology and Phylogenetic Analyses of Influenza B Virus in Thailand during 2010 to 2014

    Science.gov (United States)

    Tewawong, Nipaporn; Suwannakarn, Kamol; Prachayangprecha, Slinporn; Korkong, Sumeth; Vichiwattana, Preeyaporn; Vongpunsawad, Sompong; Poovorawan, Yong

    2015-01-01

    Influenza B virus remains a major contributor to the seasonal influenza outbreak and its prevalence has increased worldwide. We investigated the epidemiology and analyzed the full genome sequences of influenza B virus strains in Thailand between 2010 and 2014. Samples from the upper respiratory tract were collected from patients diagnosed with influenza like-illness. All samples were screened for influenza A/B viruses by one-step multiplex real-time RT-PCR. The whole genome of 53 influenza B isolates were amplified, sequenced, and analyzed. From 14,418 respiratory samples collected during 2010 to 2014, a total of 3,050 tested positive for influenza virus. Approximately 3.27% (471/14,418) were influenza B virus samples. Fifty three isolates of influenza B virus were randomly chosen for detailed whole genome analysis. Phylogenetic analysis of the HA gene showed clusters in Victoria clades 1A, 1B, 3, 5 and Yamagata clades 2 and 3. Both B/Victoria and B/Yamagata lineages were found to co-circulate during this time. The NA sequences of all isolates belonged to lineage II and consisted of viruses from both HA Victoria and Yamagata lineages, reflecting possible reassortment of the HA and NA genes. No significant changes were seen in the NA protein. The phylogenetic trees generated through the analysis of the PB1 and PB2 genes closely resembled that of the HA gene, while trees generated from the analysis of the PA, NP, and M genes showed similar topology. The NS gene exhibited the pattern of genetic reassortment distinct from those of the PA, NP or M genes. Thus, antigenic drift and genetic reassortment among the influenza B virus strains were observed in the isolates examined. Our findings indicate that the co-circulation of two distinct lineages of influenza B viruses and the limitation of cross-protection of the current vaccine formulation provide support for quadrivalent influenza vaccine in this region. PMID:25602617

  9. Mechanism of Human Influenza Virus RNA Persistence and Virion Survival in Feces: Mucus Protects Virions From Acid and Digestive Juices.

    Science.gov (United States)

    Hirose, Ryohei; Nakaya, Takaaki; Naito, Yuji; Daidoji, Tomo; Watanabe, Yohei; Yasuda, Hiroaki; Konishi, Hideyuki; Itoh, Yoshito

    2017-07-01

    Although viral RNA or infectious virions have been detected in the feces of individuals infected with human influenza A and B viruses (IAV/IBV), the mechanism of viral survival in the gastrointestinal tract remains unclear. We developed a model that attempts to recapitulate the conditions encountered by a swallowed virus. While IAV/IBV are vulnerable to simulated digestive juices (gastric acid and bile/pancreatic juice), highly viscous mucus protects viral RNA and virions, allowing the virus to retain its infectivity. Our results suggest that virions and RNA present in swallowed mucus are not inactivated or degraded by the gastrointestinal environment, allowing their detection in feces. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  10. 77 FR 63783 - Influenza Viruses Containing the Hemagglutinin from the Goose/Guangdong/1/96 Lineage

    Science.gov (United States)

    2012-10-17

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES 42 CFR Part 73 [Docket: CDC-2012-0010] Influenza Viruses... questions concerning highly pathogenic avian influenza (HPAI) H5N1 viruses that contain a hemagglutinin (HA... avian influenza (HPAI) H5N1 viruses with a mortality rate that exceeds 50 percent in hospitalized...

  11. 78 FR 9355 - Influenza Viruses Containing the Hemagglutinin From the Goose/Guangdong/1/96 Lineage

    Science.gov (United States)

    2013-02-08

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES [Docket: CDC-2012-0010] 42 CFR Part 73 Influenza Viruses... influenza (HPAI) H5N1 viruses that contain a hemagglutinin (HA) from the Goose/Guangdong/1/96 lineage, and... concerning highly pathogenic avian influenza (HPAI) H5N1 viruses that contain a hemagglutinin (HA) from the...

  12. Inactivation of Viruses and Bacteriophages as Models for Swine Hepatitis E Virus in Food Matrices.

    Science.gov (United States)

    Emmoth, Eva; Rovira, Jordi; Rajkovic, Andreja; Corcuera, Elena; Wilches Pérez, Diego; Dergel, Irene; Ottoson, Jakob R; Widén, Frederik

    2017-03-01

    Hepatitis E virus has been recognised as a food-borne virus hazard in pork products, due to its zoonotic properties. This risk can be reduced by adequate treatment of the food to inactivate food-borne viruses. We used a spectrum of viruses and bacteriophages to evaluate the effect of three food treatments: high pressure processing (HPP), lactic acid (LA) and intense light pulse (ILP) treatments. On swine liver at 400 MPa for 10 min, HPP gave log 10 reductions of ≥4.2, ≥5.0 and 3.4 for feline calicivirus (FCV) 2280, FCV wildtype (wt) and murine norovirus 1 (MNV 1), respectively. Escherichia coli coliphage ϕX174 displayed a lower reduction of 1.1, while Escherichia coli coliphage MS2 was unaffected. For ham at 600 MPa, the corresponding reductions were 4.1, 4.4, 2.9, 1.7 and 1.3 log 10 . LA treatment at 2.2 M gave log 10 reductions in the viral spectrum of 0.29-2.1 for swine liver and 0.87-3.1 for ham, with ϕX174 and MNV 1, respectively, as the most stable microorganisms. The ILP treatment gave log 10 reductions of 1.6-2.8 for swine liver, 0.97-2.2 for ham and 1.3-2.3 for sausage, at 15-60 J cm -2 , with MS2 as the most stable microorganism. The HPP treatment gave significantly (p virus reduction on swine liver than ham for the viruses at equivalent pressure/time combinations. For ILP treatment, reductions on swine liver were significantly (p virus contamination and in advice to food producers. Conservative model indicators for the pathogenic viruses could be suggested.

  13. Efficacy of influenza vaccination and tamiflu® treatment--comparative studies with Eurasian Swine influenza viruses in pigs.

    Science.gov (United States)

    Duerrwald, Ralf; Schlegel, Michael; Bauer, Katja; Vissiennon, Théophile; Wutzler, Peter; Schmidtke, Michaela

    2013-01-01

    Recent epidemiological developments demonstrated that gene segments of swine influenza A viruses can account for antigenic changes as well as reduced drug susceptibility of pandemic influenza A viruses. This raises questions about the efficacy of preventive measures against swine influenza A viruses. Here, the protective effect of vaccination was compared with that of prophylactic Tamiflu® treatment against two Eurasian swine influenza A viruses. 11-week-old pigs were infected by aerosol nebulisation with high doses of influenza virus A/swine/Potsdam/15/1981 (H1N1/1981, heterologous challenge to H1N1 vaccine strain) and A/swine/Bakum/1832/2000 (H1N2/2000, homologous challenge to H1N2 vaccine strain) in two independent trials. In each trial (i) 10 pigs were vaccinated twice with a trivalent vaccine (RESPIPORC® FLU3; 28 and 7 days before infection), (ii) another 10 pigs received 150 mg/day of Tamiflu® for 5 days starting 12 h before infection, and (iii) 12 virus-infected pigs were left unvaccinated and untreated and served as controls. Both viruses replicated efficiently in porcine respiratory organs causing influenza with fever, dyspnoea, and pneumonia. Tamiflu® treatment as well as vaccination prevented clinical signs and significantly reduced virus shedding. Whereas after homologous challenge with H1N2/2000 no infectious virus in lung and hardly any lung inflammation were detected, the virus titre was not and the lung pathology was only partially reduced in H1N1/1981, heterologous challenged pigs. Tamiflu® application did not affect these study parameters. In conclusion, all tested preventive measures provided protection against disease. Vaccination additionally prevented virus replication and histopathological changes in the lung of homologous challenged pigs.

  14. Efficacy of influenza vaccination and tamiflu® treatment--comparative studies with Eurasian Swine influenza viruses in pigs.

    Directory of Open Access Journals (Sweden)

    Ralf Duerrwald

    Full Text Available Recent epidemiological developments demonstrated that gene segments of swine influenza A viruses can account for antigenic changes as well as reduced drug susceptibility of pandemic influenza A viruses. This raises questions about the efficacy of preventive measures against swine influenza A viruses. Here, the protective effect of vaccination was compared with that of prophylactic Tamiflu® treatment against two Eurasian swine influenza A viruses. 11-week-old pigs were infected by aerosol nebulisation with high doses of influenza virus A/swine/Potsdam/15/1981 (H1N1/1981, heterologous challenge to H1N1 vaccine strain and A/swine/Bakum/1832/2000 (H1N2/2000, homologous challenge to H1N2 vaccine strain in two independent trials. In each trial (i 10 pigs were vaccinated twice with a trivalent vaccine (RESPIPORC® FLU3; 28 and 7 days before infection, (ii another 10 pigs received 150 mg/day of Tamiflu® for 5 days starting 12 h before infection, and (iii 12 virus-infected pigs were left unvaccinated and untreated and served as controls. Both viruses replicated efficiently in porcine respiratory organs causing influenza with fever, dyspnoea, and pneumonia. Tamiflu® treatment as well as vaccination prevented clinical signs and significantly reduced virus shedding. Whereas after homologous challenge with H1N2/2000 no infectious virus in lung and hardly any lung inflammation were detected, the virus titre was not and the lung pathology was only partially reduced in H1N1/1981, heterologous challenged pigs. Tamiflu® application did not affect these study parameters. In conclusion, all tested preventive measures provided protection against disease. Vaccination additionally prevented virus replication and histopathological changes in the lung of homologous challenged pigs.

  15. Efficacy of Influenza Vaccination and Tamiflu® Treatment – Comparative Studies with Eurasian Swine Influenza Viruses in Pigs

    Science.gov (United States)

    Duerrwald, Ralf; Schlegel, Michael; Bauer, Katja; Vissiennon, Théophile; Wutzler, Peter; Schmidtke, Michaela

    2013-01-01

    Recent epidemiological developments demonstrated that gene segments of swine influenza A viruses can account for antigenic changes as well as reduced drug susceptibility of pandemic influenza A viruses. This raises questions about the efficacy of preventive measures against swine influenza A viruses. Here, the protective effect of vaccination was compared with that of prophylactic Tamiflu® treatment against two Eurasian swine influenza A viruses. 11-week-old pigs were infected by aerosol nebulisation with high doses of influenza virus A/swine/Potsdam/15/1981 (H1N1/1981, heterologous challenge to H1N1 vaccine strain) and A/swine/Bakum/1832/2000 (H1N2/2000, homologous challenge to H1N2 vaccine strain) in two independent trials. In each trial (i) 10 pigs were vaccinated twice with a trivalent vaccine (RESPIPORC® FLU3; 28 and 7 days before infection), (ii) another 10 pigs received 150 mg/day of Tamiflu® for 5 days starting 12 h before infection, and (iii) 12 virus-infected pigs were left unvaccinated and untreated and served as controls. Both viruses replicated efficiently in porcine respiratory organs causing influenza with fever, dyspnoea, and pneumonia. Tamiflu® treatment as well as vaccination prevented clinical signs and significantly reduced virus shedding. Whereas after homologous challenge with H1N2/2000 no infectious virus in lung and hardly any lung inflammation were detected, the virus titre was not and the lung pathology was only partially reduced in H1N1/1981, heterologous challenged pigs. Tamiflu® application did not affect these study parameters. In conclusion, all tested preventive measures provided protection against disease. Vaccination additionally prevented virus replication and histopathological changes in the lung of homologous challenged pigs. PMID:23630601

  16. Highly pathogenic avian influenza virus (H5N1) in experimentally infected adult mute swans.

    Science.gov (United States)

    Kalthoff, Donata; Breithaupt, Angele; Teifke, Jens P; Globig, Anja; Harder, Timm; Mettenleiter, Thomas C; Beer, Martin

    2008-08-01

    Adult, healthy mute swans were experimentally infected with highly pathogenic avian influenza virus A/Cygnus cygnus/Germany/R65/2006 subtype H5N1. Immunologically naive birds died, whereas animals with preexisting, naturally acquired avian influenza virus-specific antibodies became infected asymptomatically and shed virus. Adult mute swans are highly susceptible, excrete virus, and can be clinically protected by preexposure immunity.

  17. Carbohydrate determinants in ferret conjunctiva are affected by infection with influenza H1N1 virus

    DEFF Research Database (Denmark)

    Kirkeby, Svend; Martel, Cyril; Aasted, Bent

    2013-01-01

    Carbohydrates often accomplish as cell-surface receptors for microorganisms and influenza virus preferentially binds to sialic acid through the viral haemagglutinin. The virus may attach not only to the epithelium in the airways, but also to the surface ocular epithelium.......Carbohydrates often accomplish as cell-surface receptors for microorganisms and influenza virus preferentially binds to sialic acid through the viral haemagglutinin. The virus may attach not only to the epithelium in the airways, but also to the surface ocular epithelium....

  18. Highly pathogenic avian influenza viruses and generation of novel reassortants,United States, 2014–2015

    Science.gov (United States)

    Dong-Hun Lee,; Justin Bahl,; Mia Kim Torchetti,; Mary Lea Killian,; Ip, Hon S.; David E Swayne,

    2016-01-01

    Asian highly pathogenic avian influenza A(H5N8) viruses spread into North America in 2014 during autumn bird migration. Complete genome sequencing and phylogenetic analysis of 32 H5 viruses identified novel H5N1, H5N2, and H5N8 viruses that emerged in late 2014 through reassortment with North American low-pathogenicity avian influenza viruses.

  19. A simple and rapid characterization of influenza virus isolates by monoclonal antibodies in radioimmunoassay

    International Nuclear Information System (INIS)

    Kostolansky, F.; Styk, B.; Russ, G.

    1986-01-01

    Radioimmunoassay is described with infectious allantoic fluid directly bound to solid phase, suitable for the detection and further characterization of influenza virus isolates. This simple and rapid method was applied for the description of isolates obtained from different regions of Czechoslovakia during the influenza epidemic in 1983. The results confirmed that all 13 examined isolates represented influenza A viruses possessing H3 subtype haemagglutinin very similar to haemagglutinin of influenza viruses A/Bangkok/1/79 (H3N2), A/Belgium/2/81 (H3N2) and A/Philippines/2/82 (H3N2). (author)

  20. Safety and immunogenicity of a trivalent, inactivated, mammalian cell culture-derived influenza vaccine in healthy adults, seniors, and children.

    Science.gov (United States)

    Halperin, Scott A; Smith, Bruce; Mabrouk, Taoufik; Germain, Marc; Trépanier, Pierre; Hassell, Thomas; Treanor, John; Gauthier, Richard; Mills, Elaine L

    2002-01-15

    We performed randomized, double-blind, controlled trials to assess the safety and immunogenicity of an inactivated, Madin Darby Canine Kidney (MDCK)-derived cell line produced influenza vaccine in healthy adults (19-50 years), children (3-12 years) and the elderly (> or =65 years). We studied three lots of cell culture-derived vaccine and one lot of licensed egg-derived vaccine in healthy adults (n=462), two lots of cell culture-derived vaccine and one lot of egg-derived vaccine in seniors (n=269), and one lot of each vaccine in children (n=209). Adverse events were collected during the first 3 days post-immunization; serum was collected before and 1 month after immunization. Rates of local and systemic adverse reactions were similar with both vaccines. An injection site adverse event rated at least moderate severity was reported by 21.9% of children who received the egg-derived vaccine and 25.0% of those who received the cell culture-derived vaccine. In healthy adults the proportions were 12.1 and 15.3%, respectively and 6.7 and 6.3%, respectively in seniors. Systemic events of at least moderate severity were 12.4 and 12.5% in children, 19.8 and 13.6% in healthy adults, and 14.1 and 9.7% in seniors; none of these differences were statistically significant. The antibody response against all three viruses was similar between the two vaccines. From 83 to 100% of children, healthy adults and seniors achieved hemagglutination inhibition titers in excess of 40 post-immunization. We conclude that the cell culture-derived vaccine was safe and immunogenic in children, healthy adults and seniors.

  1. Uptake and Effectiveness of a Trivalent Inactivated Influenza Vaccine in Children in Urban and Rural Kenya, 2010 to 2012.

    Science.gov (United States)

    Katz, Mark A; Lebo, Emmaculate; Emukule, Gideon O; Otieno, Nancy; Caselton, Deborah L; Bigogo, Godfrey; Njuguna, Henry; Muthoka, Philip M; Waiboci, Lilian W; Widdowson, Marc-Alain; Xu, Xiyan; Njenga, Moses K; Mott, Joshua A; Breiman, Robert F

    2016-03-01

    In Africa, recent surveillance has demonstrated a high burden of influenza, but influenza vaccine is rarely used. In Kenya, a country with a tropical climate, influenza has been shown to circulate year-round, like in other tropical countries. During 3 months in 2010 and 2011 and 2 months in 2012, the Kenya Medical Research Institute/Centers for Disease Control and Prevention-Kenya offered free injectable trivalent inactivated influenza vaccine to children 6 months to 10 years old in 2 resource-poor communities in Kenya-Kibera and Lwak (total population ~50,000). We conducted a case-control study to evaluate vaccine effectiveness (VE) in preventing laboratory-confirmed influenza associated with influenza-like illness and acute lower respiratory illness. Of the approximately 18,000 eligible children, 41%, 48% and 51% received at least 1 vaccine in 2010, 2011 and 2012, respectively; 30%, 36% and 38% were fully vaccinated. VE among fully vaccinated children was 57% [95% confidence interval (CI): 29% to 74%] during a 6-month follow-up period, 39% (95% CI: 17% to 56%) during a 9-month follow-up period and 48% (95% CI: 32% to 61%) during a 12-month follow-up period. For the 12-month follow-up period, VE was statistically significant in children Kenya, parents of nearly half of the eligible children <10 years old chose to get their children vaccinated with a free influenza vaccine. During a 12-month follow-up period, the vaccine was moderately effective in preventing medically attended influenza-associated respiratory illness.

  2. Different virucidal activities of hyperbranched quaternary ammonium coatings on poliovirus and influenza virus

    NARCIS (Netherlands)

    Tuladhar, E.; Koning, de M.C.; Fundeanu, I.; Beumer, R.R.; Duizer, E.

    2012-01-01

    Virucidal activity of immobilized quaternary ammonium compounds (IQACs) coated onto glass and plastic surfaces was tested against enveloped influenza A (H1N1) virus and nonenveloped poliovirus Sabin1. The IQACs tested were virucidal against the influenza virus within 2 min, but no virucidal effect

  3. Influenza A (H10N7) Virus Causes Respiratory Tract Disease in Harbor Seals and Ferrets

    NARCIS (Netherlands)

    van den Brand, Judith M A; Wohlsein, Peter; Herfst, Sander; Bodewes, Rogier; Pfankuche, Vanessa M; van de Bildt, Marco W G; Seehusen, Frauke; Puff, Christina; Richard, Mathilde; Siebert, Ursula; Lehnert, Kristina; Bestebroer, Theo; Lexmond, Pascal; Fouchier, Ron A M; Prenger-Berninghoff, Ellen; Herbst, Werner; Koopmans, Marion; Osterhaus, Albert D M E; Kuiken, Thijs; Baumgärtner, Wolfgang

    2016-01-01

    Avian influenza viruses sporadically cross the species barrier to mammals, including humans, in which they may cause epidemic disease. Recently such an epidemic occurred due to the emergence of avian influenza virus of the subtype H10N7 (Seal/H10N7) in harbor seals (Phoca vitulina). This epidemic

  4. Modelling the innate immune response against avian influenza virus in chicken

    NARCIS (Netherlands)

    Hagenaars, T.J.; Fischer, E.A.J.; Jansen, C.A.; Rebel, J.M.J.; Spekreijse, D.; Vervelde, L.; Backer, J.A.; Jong, de M.C.M.; Koets, A.P.

    2016-01-01

    At present there is limited understanding of the host immune response to (low pathogenic) avian influenza virus infections in poultry. Here we develop a mathematical model for the innate immune response to avian influenza virus in chicken lung, describing the dynamics of viral load,

  5. Human Infection with Avian Influenza A(H7N9) Virus - China

    Science.gov (United States)

    ... response operations Diseases Biorisk reduction Disease outbreak news Human infection with avian influenza A(H7N9) virus – China ... Region (SAR) notified WHO of a laboratory-confirmed human infection with avian influenza A(H7N9) virus and ...

  6. Influenza B viruses with mutation in the neuraminidase active site, North Carolina, USA, 2010-11.

    Science.gov (United States)

    Sleeman, Katrina; Sheu, Tiffany G; Moore, Zack; Kilpatrick, Susan; Garg, Shikha; Fry, Alicia M; Gubareva, Larisa V

    2011-11-01

    Oseltamivir is 1 of 2 antiviral medications available for the treatment of influenza B virus infections. We describe and characterize a cluster of influenza B viruses circulating in North Carolina with a mutation in the neuraminidase active site that may reduce susceptibility to oseltamivir and the investigational drug peramivir but not to zanamivir.

  7. Modelling the Innate Immune Response against Avian Influenza Virus in Chicken

    NARCIS (Netherlands)

    Hagenaars, T J; Fischer, E A J; Jansen, C A; Rebel, J M J; Spekreijse, D; Vervelde, L; Backer, J A; de Jong, M.C.M.; Koets, A P

    2016-01-01

    At present there is limited understanding of the host immune response to (low pathogenic) avian influenza virus infections in poultry. Here we develop a mathematical model for the innate immune response to avian influenza virus in chicken lung, describing the dynamics of viral load, interferon-α, -β

  8. Sparse evidence for equine or avian influenza virus infections among Mongolian adults with animal exposures

    OpenAIRE

    Khurelbaatar, Nyamdavaa; Krueger, Whitney S.; Heil, Gary L.; Darmaa, Badarchiin; Ulziimaa, Daramragchaa; Tserennorov, Damdindorj; Baterdene, Ariungerel; Anderson, Benjamin D.; Gray, Gregory C.

    2013-01-01

    In recent years, Mongolia has experienced recurrent epizootics of equine influenza virus (EIV) among its 2?1 million horses and multiple incursions of highly pathogenic avian influenza (HPAI) virus via migrating birds. No human EIV or HPAI infections have been reported. In 2009, 439 adults in Mongolia were enrolled in a population?based study of zoonotic influenza transmission. Enrollment sera were examined for serological evidence of infection with nine avian, three human, and one equine inf...

  9. Inactivation by gamma irradiation of animal viruses in simulated laboratory effluent

    International Nuclear Information System (INIS)

    Thomas, F.C.; Ouwerkerk, T.; McKercher, P.

    1982-01-01

    Several animal viruses were treated with gamma radiation from a 60 Co source under conditions which might be found in effluent from an animal disease laboratory. Swine vesicular disease virus, vesicular stomatitis virus, and blue-tongue virus were irradiated in tissues from experimentally infected animals. Pseudorabies virus, fowl plague virus, swine vesicular disease virus, and vesicular stomatitis virus were irradiated in liquid animal feces. All were tested in animals and in vitro. The D 10 values, that is, the doses required to reduce infectivity by 1 log 10 , were not apparently different from those expected from predictions based on other data and theoretical considerations. The existence of the viruses in pieces of tissues or in liquid feces made no differences in the efficacy of the gamma radiation for inactivating them. Under the ''worst case'' conditions (most protective for virus) simulated in this study, no infectious agents would survive 4.0 Mrads

  10. Replication of swine and human influenza viruses in juvenile and layer turkey hens.

    Science.gov (United States)

    Ali, Ahmed; Yassine, Hadi; Awe, Olusegun O; Ibrahim, Mahmoud; Saif, Yehia M; Lee, Chang-Won

    2013-04-12

    Since the first reported isolation of swine influenza viruses (SIVs) in turkeys in the 1980s, transmission of SIVs to turkeys was frequently documented. Recently, the 2009 pandemic H1N1 virus, that was thought to be of swine origin, was detected in turkeys with a severe drop in egg production. In this study, we assessed the infectivity of different mammalian influenza viruses including swine, pandemic H1N1 and seasonal human influenza viruses in both juvenile and layer turkeys. In addition, we investigated the potential influenza virus dissemination in the semen of experimentally infected turkey toms. Results showed that all mammalian origin influenza viruses tested can infect turkeys. SIVs were detected in respiratory and digestive tracts of both juvenile and layer turkeys. Variations in replication efficiencies among SIVs were observed especially in the reproductive tract of layer turkeys. Compared to SIVs, limited replication of seasonal human H1N1 and no detectable replication of recent human-like swine H1N2, pandemic H1N1 and seasonal human H3N2 viruses was noticed. All birds seroconverted to all tested viruses regardless of their replication level. In turkey toms, we were able to detect swine H3N2 virus in semen and reproductive tract of infected toms by real-time RT-PCR although virus isolation was not successful. These data suggest that turkey hens could be affected by diverse influenza strains especially SIVs. Moreover, the differences in the replication efficiency we demonstrated among SIVs and between SIV and human influenza viruses in layer turkeys suggest a possible use of turkeys as an animal model to study host tropism and pathogenesis of influenza viruses. Our results also indicate a potential risk of venereal transmission of influenza viruses in turkeys. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. Alternaria alternata challenge at the nasal mucosa results in eosinophilic inflammation and increased susceptibility to influenza virus infection.

    Science.gov (United States)

    Ma, M; Redes, J L; Percopo, C M; Druey, K M; Rosenberg, H F

    2018-06-01

    Eosinophils in the nasal mucosa are an elemental feature of allergic rhinitis. Our objective was to explore eosinophilic inflammation and its impact on respiratory virus infection at the nasal mucosa. Inflammation in the nasal mucosae of mice was evaluated in response to repetitive stimulation with strict intranasal volumes of a filtrate of Alternaria alternata. Mice were then challenged with influenza virus. Repetitive stimulation with A. alternata resulted in eosinophil recruitment to the nasal passages in association with elevated levels of IL-5, IL-13 and eotaxin-1; eosinophil recruitment was diminished in eotaxin-1 -/- mice, and abolished in Rag1 -/- mice. A. alternata also resulted in elevated levels of nasal wash IgA in both wild-type and eosinophil-deficient ∆dblGATA mice. Interestingly, A. alternata-treated mice responded to an influenza virus infection with profound weight loss and mortality compared to mice that received diluent alone (0% vs 100% survival, ***P < .001); the lethal response was blunted when A. alternata was heat-inactivated. Minimal differences in virus titre were detected, and eosinophils present in the nasal passages at the time of virus inoculation provided no protection against the lethal sequelae. Interestingly, nasal wash fluids from mice treated with A. alternata included more neutrophils and higher levels of pro-inflammatory mediators in response to virus challenge, among these, IL-6, a biomarker for disease severity in human influenza. Repetitive administration of A. alternata resulted in inflammation of the nasal mucosae and unanticipated morbidity and mortality in response to subsequent challenge with influenza virus. Interestingly, and in contrast to findings in the lower airways, eosinophils recruited to the nasal passages provided no protection against lethal infection. As increased susceptibility to influenza virus among individuals with rhinitis has been the subject of several clinical reports, this model may be

  12. Efficacy of a pandemic (H1N1) 2009 virus vaccine in pigs against the pandemic influenza virus is superior to commercially available swine influenza vaccines.

    NARCIS (Netherlands)

    Loeffen, W.L.A.; Stockhofe-Zurwieden, N.; Weesendorp, E.; Zoelen-Bos, van D.J.; Heutink, R.; Quak, J.; Goovaerts, D.; Heldens, J.; Maas, H.A.; Moormann, R.J.M.; Koch, G.

    2011-01-01

    In April 2009 a new influenza A/H1N1 strain, currently named “pandemic (H1N1) influenza 2009¿ (H1N1v), started the first official pandemic in humans since 1968. Several incursions of this virus in pig herds have also been reported from all over the world. Vaccination of pigs may be an option to

  13. Contemporary North American influenza H7 viruses possess human receptor specificity: Implications for virus transmissibility

    DEFF Research Database (Denmark)

    Belser, Jessica A; Blixt, Ola; Chen, Li-Mei

    2008-01-01

    Avian H7 influenza viruses from both the Eurasian and North American lineage have caused outbreaks in poultry since 2002, with confirmed human infection occurring during outbreaks in The Netherlands, British Columbia, and the United Kingdom. The majority of H7 infections have resulted in self-lim...

  14. Control of mucosal virus infection by influenza nucleoprotein-specific CD8+ cytotoxic T lymphocytes

    Directory of Open Access Journals (Sweden)

    Couch Robert B

    2007-06-01

    Full Text Available Abstract Background MHC class I-restricted CD8+ cytotoxic T lymphocytes (CTL are thought to play a major role in clearing virus and promoting recovery from influenza infection and disease. This has been demonstrated for clearance of influenza virus from the lungs of infected mice. However, human influenza infection is primarily a respiratory mucosal infection involving the nasopharynx and tracheobronchial tree. The role of CD8+ CTL directed toward the influenza nucleoprotein (NP in defense against influenza virus infection at the respiratory mucosa was evaluated in two separate adoptive transfer experiments. Methods Influenza nucleoprotein (NP-specific CD8+ CTL were generated from splenocytes obtained from Balb/c mice previously primed with influenza A/Taiwan/1/86 (H1N1 infection or with influenza A/PR/8/34 (H1N1-derived NP plasmid DNA vaccine followed by infection with A/Hong Kong/68 (H3N2 virus. After in vitro expansion by exposure to an influenza NP-vaccinia recombinant, highly purified CD8+ T cells exhibited significant lysis in vitro of P815 target cells infected with A/Hong Kong/68 (H3N2 virus while the CD8- fraction (CD4+ T cells, B cells and macrophages had no CTL activity. Purified CD8+ and CD8- T cells (1 × 107 were injected intravenously or interperitoneally into naive mice four hours prior to intranasal challenge with A/HK/68 (H3N2 virus. Results The adoptively transferred NP-vaccinia-induced CD8+ T cells caused significant reduction of virus titers in both the lungs and nasal passages when compared to CD8- cells. Neither CD8+ nor CD8- T cells from cultures stimulated with HIV gp120-vaccinia recombinant reduced virus titers. Conclusion The present data demonstrate that influenza NP-specific CD8+ CTL can play a direct role in clearance of influenza virus from the upper respiratory mucosal surfaces.

  15. [Burden of influenza virus type B and mismatch with the flu vaccine in Spain].

    Science.gov (United States)

    Eiros-Bouza, Jose Ma; Pérez-Rubio, Alberto

    2015-02-01

    Since the 80s two lineages of type B viruses are co - circulating in the world. Antigenic differences between them are important and it leads to lack of cross-reactivity. The impact on the burden of disease due to influenza B virus, poor foresight in estimating which of the two lineages of B viruses circulate in the season, and the consequent lack of immunity in case of including the wrong strain make that the availability of the quadrivalent vaccine is very useful. The aim of this paper is to analyze the past influenza seasons in Spain to assess the burden of disease, divergence between the vaccine strain and the circulating B and viral characteristics associated with type B in each seasonal epidemic. Review of all reports issued by the Influenza Surveillance System in Spain since the 2003-2004 season to 2012-2013. Over the past influenza seasons, although type A was present mostly, circulation of influenza B virus in each season was observed, even being co - dominant in some of them. In a high number of seasons the divergence between the vaccine strain and the circulating strain lineage has been observed The protective effect of influenza vaccine has varied depending on the type / subtype of influenza virus studied. The vaccine effectiveness against influenza infection by influenza B virus has varied greatly depending on the season analyzed.

  16. Avian Influenza virus glycoproteins restrict virus replication and spread through human airway epithelium at temperatures of the proximal airways.

    Directory of Open Access Journals (Sweden)

    Margaret A Scull

    2009-05-01

    Full Text Available Transmission of avian influenza viruses from bird to human is a rare event even though avian influenza viruses infect the ciliated epithelium of human airways in vitro and ex vivo. Using an in vitro model of human ciliated airway epithelium (HAE, we demonstrate that while human and avian influenza viruses efficiently infect at temperatures of the human distal airways (37 degrees C, avian, but not human, influenza viruses are restricted for infection at the cooler temperatures of the human proximal airways (32 degrees C. These data support the hypothesis that avian influenza viruses, ordinarily adapted to the temperature of the avian enteric tract (40 degrees C, rarely infect humans, in part due to differences in host airway regional temperatures. Previously, a critical residue at position 627 in the avian influenza virus polymerase subunit, PB2, was identified as conferring temperature-dependency in mammalian cells. Here, we use reverse genetics to show that avianization of residue 627 attenuates a human virus, but does not account for the different infection between 32 degrees C and 37 degrees C. To determine the mechanism of temperature restriction of avian influenza viruses in HAE at 32 degrees C, we generated recombinant human influenza viruses in either the A/Victoria/3/75 (H3N2 or A/PR/8/34 (H1N1 genetic background that contained avian or avian-like glycoproteins. Two of these viruses, A/Victoria/3/75 with L226Q and S228G mutations in hemagglutinin (HA and neuraminidase (NA from A/Chick/Italy/1347/99 and A/PR/8/34 containing the H7 and N1 from A/Chick/Italy/1347/99, exhibited temperature restriction approaching that of wholly avian influenza viruses. These data suggest that influenza viruses bearing avian or avian-like surface glycoproteins have a reduced capacity to establish productive infection at the temperature of the human proximal airways. This temperature restriction may limit zoonotic transmission of avian influenza viruses and

  17. Guinea pig model for evaluating the potential public health risk of swine and avian influenza viruses.

    Directory of Open Access Journals (Sweden)

    Yipeng Sun

    Full Text Available BACKGROUND: The influenza viruses circulating in animals sporadically transmit to humans and pose pandemic threats. Animal models to evaluate the potential public health risk potential of these viruses are needed. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the guinea pig as a mammalian model for the study of the replication and transmission characteristics of selected swine H1N1, H1N2, H3N2 and avian H9N2 influenza viruses, compared to those of pandemic (H1N1 2009 and seasonal human H1N1, H3N2 influenza viruses. The swine and avian influenza viruses investigated were restricted to the respiratory system of guinea pigs and shed at high titers in nasal tracts without prior adaptation, similar to human strains. None of the swine and avian influenza viruses showed transmissibility among guinea pigs; in contrast, pandemic (H1N1 2009 virus transmitted from infected guinea pigs to all animals and seasonal human influenza viruses could also horizontally transmit in guinea pigs. The analysis of the receptor distribution in the guinea pig respiratory tissues by lectin histochemistry indicated that both SAα2,3-Gal and SAα2,6-Gal receptors widely presented in the nasal tract and the trachea, while SAα2,3-Gal receptor was the main receptor in the lung. CONCLUSIONS/SIGNIFICANCE: We propose that the guinea pig could serve as a useful mammalian model to evaluate the potential public health threat of swine and avian influenza viruses.

  18. Guinea pig model for evaluating the potential public health risk of swine and avian influenza viruses.

    Science.gov (United States)

    Sun, Yipeng; Bi, Yuhai; Pu, Juan; Hu, Yanxin; Wang, Jingjing; Gao, Huijie; Liu, Linqing; Xu, Qi; Tan, Yuanyuan; Liu, Mengda; Guo, Xin; Yang, Hanchun; Liu, Jinhua

    2010-11-23

    The influenza viruses circulating in animals sporadically transmit to humans and pose pandemic threats. Animal models to evaluate the potential public health risk potential of these viruses are needed. We investigated the guinea pig as a mammalian model for the study of the replication and transmission characteristics of selected swine H1N1, H1N2, H3N2 and avian H9N2 influenza viruses, compared to those of pandemic (H1N1) 2009 and seasonal human H1N1, H3N2 influenza viruses. The swine and avian influenza viruses investigated were restricted to the respiratory system of guinea pigs and shed at high titers in nasal tracts without prior adaptation, similar to human strains. None of the swine and avian influenza viruses showed transmissibility among guinea pigs; in contrast, pandemic (H1N1) 2009 virus transmitted from infected guinea pigs to all animals and seasonal human influenza viruses could also horizontally transmit in guinea pigs. The analysis of the receptor distribution in the guinea pig respiratory tissues by lectin histochemistry indicated that both SAα2,3-Gal and SAα2,6-Gal receptors widely presented in the nasal tract and the trachea, while SAα2,3-Gal receptor was the main receptor in the lung. We propose that the guinea pig could serve as a useful mammalian model to evaluate the potential public health threat of swine and avian influenza viruses.

  19. Report on Influenza A and B Viruses: Their Coinfection in a Saudi Leukemia Patient

    Directory of Open Access Journals (Sweden)

    Fahad N. Almajhdi

    2013-01-01

    Full Text Available Purpose. Influenza A and B viruses are the leading cause of respiratory infections in children worldwide, particularly in developing countries. There is a lack of data on coinfection of influenza A and B viruses circulating in Saudi Arabia. In this study, we aimed to identify the circulation of influenza viruses that contribute to respiratory tract infections in Saudi children. Methods. We collected 80 nasopharyngeal aspirates (NPAs from hospitalized children with acute respiratory illness (ARI at Riyadh during the period extended from October 2010 till April 2011. Samples were tested for the common respiratory viruses including influenza viruses by RT-PCR. Results. Overall, 6 samples were found positive for influenza A and/or B viruses. Among these positive clinical samples, only one collected sample from a female one-year-old immunocompromised child with leukemia showed a coinfection with influenza A and B viruses. In present study coinfection was confirmed by inoculation of the clinical specimen in specific pathogenfree embryonating chicken eggs and identification of the virus isolates by hemagglutination and one-step RT-PCR. Conclusion. This study opens the scene for studying the role of influenza virus’s coinfection in disease severity and virus evolution. Further studies are required to better understand the clinical importance of viral coinfection.

  20. Immunogenicity, safety and tolerability of inactivated trivalent influenza vaccine in overweight and obese children.

    Science.gov (United States)

    Esposito, Susanna; Giavoli, Claudia; Trombetta, Claudia; Bianchini, Sonia; Montinaro, Valentina; Spada, Anna; Montomoli, Emanuele; Principi, Nicola

    2016-01-02

    Obesity may be a risk factor for increased hospitalization and deaths from infections due to respiratory pathogens. Additionally, obese patients appear to have impaired immunity after some vaccinations. To evaluate the immunogenicity, safety and tolerability of an inactivated trivalent influenza vaccine (TIV) in overweight and obese children, 28 overweight/obese pediatric patients and 23 healthy normal weight controls aged 3-14 years received a dose of TIV. Four weeks after vaccine administration, significantly higher seroprotection rates against the A/H1N1 strain were observed among overweight/obese children compared with normal weight controls (pvaccination, similar or slightly higher seroconversion and seroprotection rates against the A/H1N1 and A/H3N2 strains were detected in overweight/obese than in normal weight children, whereas significantly higher rates of seroconversion and seroprotection against the B strain were found in overweight/obese patients than in normal weight controls (pvaccine administration (pchildren, antibody response to TIV administration is similar or slightly higher than that evidenced in normal weight subjects of similar age and this situation persists for at least 4 months after vaccine administration in the presence of a favorable safety profile. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Progress on adenovirus-vectored universal influenza vaccines

    OpenAIRE

    Xiang, Kui; Ying, Guan; Yan, Zhou; Shanshan, Yan; Lei, Zhang; Hongjun, Li; Maosheng, Sun

    2015-01-01

    Influenza virus (IFV) infection causes serious health problems and heavy financial burdens each year worldwide. The classical inactivated influenza virus vaccine (IIVV) and live attenuated influenza vaccine (LAIV) must be updated regularly to match the new strains that evolve due to antigenic drift and antigenic shift. However, with the discovery of broadly neutralizing antibodies that recognize conserved antigens, and the CD8+ T cell responses targeting viral internal proteins nucleoprotein ...

  2. Accumulation of a low pathogenic avian influenza virus in zebra mussels (Dreissena polymorpha).

    Science.gov (United States)

    Stumpf, Petra; Failing, Klaus; Papp, Tibor; Nazir, Jawad; Böhm, Reinhard; Marschang, Rachel E

    2010-12-01

    In order to investigate the potential role of mussels as a vector of influenza A viruses, we exposed zebra mussels (Dreissena polymorpha) to natural lake water containing a low pathogenic H5N1 avian influenza virus. Mussels were kept in water containing virus for 48 hr, then transferred into fresh water for another 14 days. Virus detection in mussels and water samples was performed by quantitative real-time reverse transcriptase-PCR (qRRT-PCR) and egg culture methods. Virus uptake was detected in all of the mussel groups that were exposed to virus. Even after 14 days in fresh water, virus could still be detected in shellfish material by both qRRT-PCR and egg culture methods. The present study demonstrates that zebra mussels are capable of accumulating influenza A viruses from the surrounding water and that these viruses remain in the mussels over an extended period of time.

  3. Inactivation of Zika virus in human breast milk by prolonged storage or pasteurization.

    Science.gov (United States)

    Pfaender, Stephanie; Vielle, Nathalie J; Ebert, Nadine; Steinmann, Eike; Alves, Marco P; Thiel, Volker

    2017-01-15

    Zika virus infection during pregnancy poses a serious risk for pregnant women as it can cause severe birth defects. Even though the virus is mainly transmitted via mosquitos, human-to-human transmission has been described. Infectious viral particles have been detected in breast milk of infected women which raised concerns regarding the safety of breastfeeding in areas of Zika virus transmission or in case of a suspected or confirmed Zika virus infection. In this study, we show that Zika virus is effectively inactivated in human breast milk after prolonged storage or upon pasteurization of milk. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  4. Microculture virus titration--a simple colourimetric assay for influenza virus titration.

    Science.gov (United States)

    Levi, R; Beeor-Tzahar, T; Arnon, R

    1995-03-01

    Influenza antigens can be detected by several well established methods. However, when it is important to determine the titre of infective virions, a bioassay should be employed. The standard and the most widely used tests for influenza infectivity are titration carried out in embryonated hen eggs, or the plaque assay employing tissue culture techniques. A simple colourimetric assay for influenza virus detection and titration is described. Samples of allantoic fluid or mice lung homogenates were used to infect MDCK cultures in microplate wells. After an incubation period, the tetrazolium (MTT) colourimetric assay was used to determine cell viability, and when compared to untreated culture control enabled the detection and titration of several influenza strains. When samples were assayed simultaneously in embryonated eggs and by the MCVT method, good correlation in determined titres was obtained. The availability of an additional method for influenza titration allows more flexibility in the choice of titration method according to the specific needs of the study. Furthermore, this method lends itself to full automatization. Similar procedures should also be applicable to titration of other cytopathic viruses.

  5. Antiviral activity of maca (Lepidium meyenii) against human influenza virus.

    Science.gov (United States)

    Del Valle Mendoza, Juana; Pumarola, Tomàs; Gonzales, Libertad Alzamora; Del Valle, Luis J

    2014-09-01

    To investigate antiviral activity of maca to reduce viral load in Madin-Darby canine kidney (MDCK) cells infected with influenza type A and B viruses (Flu-A and Flu-B, respectively). Maca were extracted with methanol (1:2, v/v). The cell viability and toxicity of the extracts were evaluated on MDCK cells using method MTT assay. Antiviral activity of compounds against Flu-A and Flu-B viruses was assayed using a test for determining the inhibition of the cytopathic effect on cell culture and multiplex RT-PCR. The methanol extract of maca showed low cytotoxicity and inhibited influenza-induced cytopathic effect significantly, while viral load was reduced via inhibition of viral growth in MDCK infected cells. Maca contains potent inhibitors of Flu-A and Flu-B with a selectivity index [cytotoxic concentration 50%/IC50] of 157.4 and 110.5, respectively. In vitro assays demonstrated that maca has antiviral activity not only against Flu-A (like most antiviral agents) but also Flu-B viruses, providing remarkable therapeutic benefits. Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  6. Seroprevalence survey of H9N2 avian influenza virus in backyard chickens around the Caspian Sea in Iran

    OpenAIRE

    Hadipour,MM

    2010-01-01

    Since 1998, an epidemic of avian influenza occurred in the Iranian poultry industry. The identified agent presented low pathogenicity, and was subtyped as an H9N2 avian influenza virus. Backyard chickens can play an important role in the epidemiology of H9N2 avian influenza virus infection. Close contact of backyard chickens with migratory birds, especially with aquatic birds, as well as neighboring poultry farms, may pose the risk of transmitting avian influenza virus, but little is known ab...

  7. Multisegment one-step RT-PCR fluorescent labeling of influenza A virus genome for use in diagnostic microarray applications

    Energy Technology Data Exchange (ETDEWEB)

    Vasin, A V; Plotnikova, M A; Klotchenko, S A; Elpaeva, E A; Komissarov, A B; Egorov, V V; Kiselev, O I [Research Institute of Influenza of the Ministry of Health and Social Development of the Russian Federation, 15/17 Prof. Popova St., St. Petersburg (Russian Federation); Sandybaev, N T; Chervyakova, O V; Strochkov, V M; Taylakova, E T; Koshemetov, J K; Mamadaliev, S M, E-mail: vasin@influenza.spb.ru [Research Institute for Biological Safety Problems of the RK NBC/SC ME and S RK, Gvardeiskiy (Kazakhstan)

    2011-04-01

    Microarray technology is one of the most challenging methods of influenza A virus subtyping, which is based on the antigenic properties of viral surface glycoproteins - hemagglutinin and neuraminidase. On the example of biochip for detection of influenza A/H5N1 virus we showed the possibility of using multisegment RTPCR method for amplification of fluorescently labeled cDNA of all possible influenza A virus subtypes with a single pair of primers in influenza diagnostic microarrays.

  8. Modeling the airborne survival of influenza virus in a residential setting: the impacts of home humidification

    Science.gov (United States)

    2010-01-01

    Background Laboratory research studies indicate that aerosolized influenza viruses survive for longer periods at low relative humidity (RH) conditions. Further analysis has shown that absolute humidity (AH) may be an improved predictor of virus survival in the environment. Maintaining airborne moisture levels that reduce survival of the virus in the air and on surfaces could be another tool for managing public health risks of influenza. Methods A multi-zone indoor air quality model was used to evaluate the ability of portable humidifiers to control moisture content of the air and the potential related benefit of decreasing survival of influenza viruses in single-family residences. We modeled indoor AH and influenza virus concentrations during winter months (Northeast US) using the CONTAM multi-zone indoor air quality model. A two-story residential template was used under two different ventilation conditions - forced hot air and radiant heating. Humidity was evaluated on a room-specific and whole house basis. Estimates of emission rates for influenza virus were particle-size specific and derived from published studies and included emissions during both tidal breathing and coughing events. The survival of the influenza virus was determined based on the established relationship between AH and virus survival. Results The presence of a portable humidifier with an output of 0.16 kg water per hour in the bedroom resulted in an increase in median sleeping hours AH/RH levels of 11 to 19% compared to periods without a humidifier present. The associated percent decrease in influenza virus survival was 17.5 - 31.6%. Distribution of water vapor through a residence was estimated to yield 3 to 12% increases in AH/RH and 7.8-13.9% reductions in influenza virus survival. Conclusion This modeling analysis demonstrates the potential benefit of portable residential humidifiers in reducing the survival of aerosolized influenza virus by controlling humidity indoors. PMID:20815876

  9. Modeling the airborne survival of influenza virus in a residential setting: the impacts of home humidification

    Directory of Open Access Journals (Sweden)

    Myatt Theodore A

    2010-09-01

    Full Text Available Abstract Background Laboratory research studies indicate that aerosolized influenza viruses survive for longer periods at low relative humidity (RH conditions. Further analysis has shown that absolute humidity (AH may be an improved predictor of virus survival in the environment. Maintaining airborne moisture levels that reduce survival of the virus in the air and on surfaces could be another tool for managing public health risks of influenza. Methods A multi-zone indoor air quality model was used to evaluate the ability of portable humidifiers to control moisture content of the air and the potential related benefit of decreasing survival of influenza viruses in single-family residences. We modeled indoor AH and influenza virus concentrations during winter months (Northeast US using the CONTAM multi-zone indoor air quality model. A two-story residential template was used under two different ventilation conditions - forced hot air and radiant heating. Humidity was evaluated on a room-specific and whole house basis. Estimates of emission rates for influenza virus were particle-size specific and derived from published studies and included emissions during both tidal breathing and coughing events. The survival of the influenza virus was determined based on the established relationship between AH and virus survival. Results The presence of a portable humidifier with an output of 0.16 kg water per hour in the bedroom resulted in an increase in median sleeping hours AH/RH levels of 11 to 19% compared to periods without a humidifier present. The associated percent decrease in influenza virus survival was 17.5 - 31.6%. Distribution of water vapor through a residence was estimated to yield 3 to 12% increases in AH/RH and 7.8-13.9% reductions in influenza virus survival. Conclusion This modeling analysis demonstrates the potential benefit of portable residential humidifiers in reducing the survival of aerosolized influenza virus by controlling humidity

  10. Analytical detection of influenza A(H3N2)v and other A variant viruses from the USA by rapid influenza diagnostic tests.

    Science.gov (United States)

    Balish, Amanda; Garten, Rebecca; Klimov, Alexander; Villanueva, Julie

    2013-07-01

    The performance of rapid influenza diagnostic tests (RIDTs) that detect influenza viral nucleoprotein (NP) antigen has been reported to be variable. Recent human infections with variant influenza A viruses that are circulating in pigs prompted the investigation of the analytical reactivity of RIDTs with these variant viruses. To determine analytical reactivity of seven FDA-cleared RIDTs with influenza A variant viruses in comparison with the reactivity with recently circulating seasonal influenza A viruses. Tenfold serial dilutions of cell culture-grown seasonal and variant influenza A viruses were prepared and tested in duplicate with seven RIDTs. All RIDTs evaluated in this study detected the seasonal influenza A(H3N2) virus, although detection limits varied among assays. All but one examined RIDT identified the influenza A(H1N1)pdm09 virus. However, only four of seven RIDTs detected all influenza A(H3N2)v, A(H1N2)v, and A(H1N1)v viruses. Reduced sensitivity of RIDTs to variant influenza viruses may be due to amino acid differences between the NP proteins of seasonal viruses and the NP proteins from viruses circulating in pigs. Clinicians should be aware of the limitations of RIDTs to detect influenza A variant viruses. Specimens from patients with influenza-like illness in whom H3N2v is suspected should be sent to public health laboratories for additional diagnostic testing. Published 2012. This article is a US Government work and is in the public domain in the USA.

  11. Influenza nucleoprotein delivered with aluminium salts protects mice from an influenza A virus that expresses an altered nucleoprotein sequence.

    Directory of Open Access Journals (Sweden)

    Megan K L Macleod

    Full Text Available Influenza virus poses a difficult challenge for protective immunity. This virus is adept at altering its surface proteins, the proteins that are the targets of neutralizing antibody. Consequently, each year a new vaccine must be developed to combat the current recirculating strains. A universal influenza vaccine that primes specific memory cells that recognise conserved parts of the virus could prove to be effective against both annual influenza variants and newly emergent potentially pandemic strains. Such a vaccine will have to contain a safe and effective adjuvant that can be used in individuals of all ages. We examine protection from viral challenge in mice vaccinated with the nucleoprotein from the PR8 strain of influenza A, a protein that is highly conserved across viral subtypes. Vaccination with nucleoprotein delivered with a universally used and safe adjuvant, composed of insoluble aluminium salts, provides protection against viruses that either express the same or an altered version of nucleoprotein. This protection correlated with the presence of nucleoprotein specific CD8 T cells in the lungs of infected animals at early time points after infection. In contrast, immunization with NP delivered with alum and the detoxified LPS adjuvant, monophosphoryl lipid A, provided some protection to the homologous viral strain but no protection against infection by influenza expressing a variant nucleoprotein. Together, these data point towards a vaccine solution for all influenza A subtypes.

  12. Fluorescent dye labeled influenza virus mainly infects innate immune cells and activated lymphocytes and can be used in cell-mediated immune response assay

    OpenAIRE

    Xie, Dongxu

    2009-01-01

    Early results have recognized that influenza virus infects the innate and adaptive immune cells. The data presented in this paper demonstrated that influenza virus labeled with fluorescent dye not only retained the ability to infect and replicate in host cells, but also stimulated a similar human immune response as did unlabeled virus. Influenza virus largely infected the innate and activated adaptive immune cells. Influenza B type virus was different from that of A type virus. B type virus w...

  13. Immune responses to influenza virus and its correlation to age and inherited factors

    Directory of Open Access Journals (Sweden)

    Azadeh Bahadoran

    2016-11-01

    Full Text Available Influenza viruses belong to the family Orthomyxoviridae of enveloped viruses and are an important cause of respiratory infections worldwide. The influenza virus is able to infect a wide variety species as diverse as poultry, marine, pigs, horses and humans. Upon infection with influenza virus the innate immunity plays a critical role in efficient and rapid control of viral infections as well as in adaptive immunity initiation. The humoral immune system produces antibodies against different influenza antigens, of which the HA-specific antibody is the most important for neutralization of the virus and thus prevention of illness. Cell mediated immunity including CD4+ helper T cells and CD8+ cytotoxic T cells are the other arms of adaptive immunity induced upon influenza virus infection. The complex inherited factors and age related changes are associated with the host immune responses. Here, we review the different components of immune responses against influenza virus. Additionally, the correlation of the immune response to age and inherited factors has been discussed. These determinations lead to a better understanding of the limitations of immune responses for developing improved vaccines to control influenza virus infection.

  14. Susceptibility of influenza viruses circulating in Western Saudi Arabia to neuraminidase inhibitors

    Directory of Open Access Journals (Sweden)

    Ahmed M. Tolah

    2016-04-01

    Full Text Available Objectives: To investigate the sensitivity of circulating influenza viruses in Western Saudi Arabia to neuraminidase inhibitors (NAIs; mainly, zanamivir and oseltamivir. Methods: Respiratory samples were collected from patients presenting with respiratory symptoms to King Abdulaziz University Hospital, Jeddah, Kingdom of Saudi Arabia (KSA between September 2013 and October 2014. All samples were tested prospectively by real-time reverse-transcription polymerase chain reaction for influenza A and B viruses. Positive samples were then inoculated on Madin-Darby Canine Kidney (MDCK cells and isolated viruses were examined for their sensitivity to NAIs using fluorescent neuraminidase inhibition assay. Results: Out of 406 tested samples, 25 samples (6.2% were positive for influenza A/pdmH1N1 virus, one sample (0.25% was positive for influenza A/H3N2 virus, and 7 samples (1.7% were positive for influenza B Yamagata-like virus. Screening of isolated influenza A and B viruses (9 out of 33 for their sensitivity to NAIs showed no significant resistance to available NAIs. Conclusion: Our results show that circulating influenza viruses in Jeddah are still sensitive to NAIs.

  15. A duplex real-time RT-PCR assay for detecting H5N1 avian influenza virus and pandemic H1N1 influenza virus

    OpenAIRE

    Kang, Xiao-ping; Jiang, Tao; Li, Yong-qiang; Lin, Fang; Liu, Hong; Chang, Guo-hui; Zhu, Qing-yu; Qin, E-de; Qin, Cheng-feng; Yang, Yin-hui

    2010-01-01

    Abstract A duplex real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay was improved for simultaneous detection of highly pathogenic H5N1 avian influenza virus and pandemic H1N1 (2009) influenza virus, which is suitable for early diagnosis of influenza-like patients and for epidemiological surveillance. The sensitivity of this duplex real-time RT-PCR assay was 0.02 TCID50 (50% tissue culture infective dose) for H5N1 and 0.2 TCID50 for the pandemic H1N1, which was the same a...

  16. Protective immunity and safety of a genetically modified influenza virus vaccine.

    Directory of Open Access Journals (Sweden)

    Rafael Polidoro Alves Barbosa

    Full Text Available Recombinant influenza viruses are promising viral platforms to be used as antigen delivery vectors. To this aim, one of the most promising approaches consists of generating recombinant viruses harboring partially truncated neuraminidase (NA segments. To date, all studies have pointed to safety and usefulness of this viral platform. However, some aspects of the inflammatory and immune responses triggered by those recombinant viruses and their safety to immunocompromised hosts remained to be elucidated. In the present study, we generated a recombinant influenza virus harboring a truncated NA segment (vNA-Δ and evaluated the innate and inflammatory responses and the safety of this recombinant virus in wild type or knock-out (KO mice with impaired innate (Myd88 -/- or acquired (RAG -/- immune responses. Infection using truncated neuraminidase influenza virus was harmless regarding lung and systemic inflammatory response in wild type mice and was highly attenuated in KO mice. We also demonstrated that vNA-Δ infection does not induce unbalanced cytokine production that strongly contributes to lung damage in infected mice. In addition, the recombinant influenza virus was able to trigger both local and systemic virus-specific humoral and CD8+ T cellular immune responses which protected immunized mice against the challenge with a lethal dose of homologous A/PR8/34 influenza virus. Taken together, our findings suggest and reinforce the safety of using NA deleted influenza viruses as antigen delivery vectors against human or veterinary pathogens.

  17. Trends in global warming and evolution of nucleoproteins from influenza A viruses since 1918.

    Science.gov (United States)

    Yan, S; Wu, G

    2010-12-01

    Global warming affects not only the environment where we live, but also all living species to different degree, including influenza A virus. We recently conducted several studies on the possible impact of global warming on the protein families of influenza A virus. More studies are needed in order to have a full picture of the impact of global warming on living organisms, especially its effect on viruses. In this study, we correlate trends in global warming with evolution of the nucleoprotein from influenza A virus and then analyse the trends with respect to northern/southern hemispheres, virus subtypes and sampling species. The results suggest that global warming may have an impact on the evolution of the nucleoprotein from influenza A virus. © 2010 Blackwell Verlag GmbH.

  18. Photodynamic inactivation of rubella virus enhances recombination with a latent virus of a baby hamster kidney cell line BHK21

    International Nuclear Information System (INIS)

    Yamamoto, Nobuto; Urade, Masahiro

    1989-01-01

    Rubella virus is very sensitive to photodynamic action. When tested with 1.2 x 10 -5 M toluidine blue and 8 W fluorescent lamp at a fluence of 11 W/m 2 , inactivation kinetics showed a linear single hit curve with a k value of 1.48 min -1 . Photodynamic inactivation of rubella virus greatly enhanced recombination with a latent virus (R-virus) of baby hamster kidney BHK21 cells. In contrast, no hybrids were detected in lysates of the cells infected with either UV-treated or untreated rubella virus. Therefore, hybrid viruses were readily detected only in lysates of BHK21 cells infected with photodynamically treated rubella virus. Photodynamic damage of rubella virus genomes generated a new hybrid type (hybrid type 3) in addition to a previously described type 2 hybrid (formerly designated as HPV-RV variant). Although both of these hybrid types carry the CF antigens of rubella virus, plaque forming ability of type 3 hybrid is neutralized neither by anti-rubella serum nor by anti-latent virus serum while type 2 hybrid is neutralized by anti-latent virus serum. (author)

  19. Inactivation of human immunodeficiency virus (HIV) by ionizing radiation in body fluids and serological evidence

    International Nuclear Information System (INIS)

    Bigbee, P.D.; Sarin, P.S.; Humphreys, J.C.; Eubanks, W.G.; Sun, D.; Hocken, D.G.; Thornton, A.; Adams, D.E.; Simic, M.G.

    1989-01-01

    A method to use ionizing radiation to inactivate HIV (Human Immunodeficiency Virus) in human body fluids was studied in an effort to reduce the risk of accidental infection to forensic science laboratory workers. Experiments conducted indicate that an X-ray absorbed dose of 25 krad was required to completely inactivate HIV. This does not alter forensically important constituents such as enzymes and proteins in body fluids. This method of inactivation of HIV cannot be used on body fluids which will be subjected to deoxyribonucleic acid (DNA) typing

  20. Buffer AVL Alone Does Not Inactivate Ebola Virus in a Representative Clinical Sample Type.

    Science.gov (United States)

    Smither, Sophie J; Weller, Simon A; Phelps, Amanda; Eastaugh, Lin; Ngugi, Sarah; O'Brien, Lyn M; Steward, Jackie; Lonsdale, Steve G; Lever, Mark S

    2015-10-01

    Rapid inactivation of Ebola virus (EBOV) is crucial for high-throughput testing of clinical samples in low-resource, outbreak scenarios. The EBOV inactivation efficacy of Buffer AVL (Qiagen) was tested against marmoset serum (EBOV concentration of 1 × 10(8) 50% tissue culture infective dose per milliliter [TCID50 · ml(-1)]) and murine blood (EBOV concentration of 1 × 10(7) TCID50 · ml(-1)) at 4:1 vol/vol buffer/sample ratios. Posttreatment cell culture and enzyme-linked immunosorbent assay (ELISA) analysis indicated that treatment with Buffer AVL did not inactivate EBOV in 67% of samples, indicating that Buffer AVL, which is designed for RNA extraction and not virus inactivation, cannot be guaranteed to inactivate EBOV in diagnostic samples. Murine blood samples treated with ethanol (4:1 [vol/vol] ethanol/sample) or heat (60°C for 15 min) also showed no viral inactivation in 67% or 100% of samples, respectively. However, combined Buffer AVL and ethanol or Buffer AVL and heat treatments showed total viral inactivation in 100% of samples tested. The Buffer AVL plus ethanol and Buffer AVL plus heat treatments were also shown not to affect the extraction of PCR quality RNA from EBOV-spiked murine blood samples. © Crown copyright 2015.

  1. Protection against Multiple Subtypes of Influenza Viruses by Virus-Like Particle Vaccines Based on a Hemagglutinin Conserved Epitope

    Directory of Open Access Journals (Sweden)

    Shaoheng Chen

    2015-01-01

    Full Text Available We selected the conserved sequence in the stalk region of influenza virus hemagglutinin (HA trimmer, the long alpha helix (LAH, as the vaccine candidate sequence, and inserted it into the major immunodominant region (MIR of hepatitis B virus core protein (HBc, and, by using the E. coli expression system, we prepared a recombinant protein vaccine LAH-HBc in the form of virus-like particles (VLP. Intranasal immunization of mice with this LAH-HBc VLP plus cholera toxin B subunit with 0.2% of cholera toxin (CTB* adjuvant could effectively elicit humoral and cellular immune responses and protect mice against a lethal challenge of homologous influenza viruses (A/Puerto Rico/8/1934 (PR8 (H1N1. In addition, passage of the immune sera containing specific antibodies to naïve mice rendered them resistant against a lethal homologous challenge. Immunization with LAH-HBc VLP vaccine plus CTB* adjuvant could also fully protect mice against a lethal challenge of the 2009 pandemic H1N1 influenza virus or the avian H9N2 virus and could partially protect mice against a lethal challenge of the avian H5N1 influenza virus. This study demonstrated that the LAH-HBc VLP vaccine based on a conserved sequence of the HA trimmer stalk region is a promising candidate vaccine for developing a universal influenza vaccine against multiple influenza viruses infections.

  2. Sensitization with vaccinia virus encoding H5N1 hemagglutinin restores immune potential against H5N1 influenza virus.

    Science.gov (United States)

    Yasui, Fumihiko; Itoh, Yasushi; Ikejiri, Ai; Kitabatake, Masahiro; Sakaguchi, Nobuo; Munekata, Keisuke; Shichinohe, Shintaro; Hayashi, Yukiko; Ishigaki, Hirohito; Nakayama, Misako; Sakoda, Yoshihiro; Kida, Hiroshi; Ogasawara, Kazumasa; Kohara, Michinori

    2016-11-28

    H5N1 highly pathogenic avian influenza (H5N1 HPAI) virus causes elevated mortality compared with seasonal influenza viruses like H1N1 pandemic influenza (H1N1 pdm) virus. We identified a mechanism associated with the severe symptoms seen with H5N1 HPAI virus infection. H5N1 HPAI virus infection induced a decrease of dendritic cell number in the splenic extrafollicular T-cell zone and impaired formation of the outer layers of B-cell follicles, resulting in insufficient levels of antibody production after infection. However, in animals vaccinated with a live recombinant vaccinia virus expressing the H5 hemagglutinin, infection with H5N1 HPAI virus induced parafollicular dendritic cell accumulation and efficient antibody production. These results indicate that a recombinant vaccinia encoding H5 hemagglutinin gene does not impair dendritic cell recruitment and can be a useful vaccine candidate.

  3. Weighing serological evidence of human exposure to animal influenza viruses - a literature review.

    Science.gov (United States)

    Sikkema, Reina Saapke; Freidl, Gudrun Stephanie; de Bruin, Erwin; Koopmans, Marion

    2016-11-03

    Assessing influenza A virus strains circulating in animals and their potential to cross the species barrier and cause human infections is important to improve human influenza surveillance and preparedness. We reviewed studies describing serological evidence of human exposure to animal influenza viruses. Comparing serological data is difficult due to a lack of standardisation in study designs and in laboratory methods used in published reports. Therefore, we designed a scoring system to assess and weigh specificity of obtained serology results in the selected articles. Many studies report reliable evidence of antibodies to swine influenza viruses among persons occupationally exposed to pigs. Most avian influenza studies target H5, H7 and H9 subtypes and most serological evidence of human exposure to avian influenza viruses is reported for these subtypes. Avian influenza studies receiving a low grade in this review often reported higher seroprevalences in humans compared with studies with a high grade. Official surveillance systems mainly focus on avian H5 and H7 viruses. Swine influenza viruses and avian subtypes other than H5 and H7 (emphasising H9) should be additionally included in official surveillance systems. Surveillance efforts should also be directed towards understudied geographical areas, such as Africa and South America. This article is copyright of The Authors, 2016.

  4. Weighing serological evidence of human exposure to animal influenza viruses − a literature review

    Science.gov (United States)

    Sikkema, Reina Saapke; Freidl, Gudrun Stephanie; de Bruin, Erwin; Koopmans, Marion

    2016-01-01

    Assessing influenza A virus strains circulating in animals and their potential to cross the species barrier and cause human infections is important to improve human influenza surveillance and preparedness. We reviewed studies describing serological evidence of human exposure to animal influenza viruses. Comparing serological data is difficult due to a lack of standardisation in study designs and in laboratory methods used in published reports. Therefore, we designed a scoring system to assess and weigh specificity of obtained serology results in the selected articles. Many studies report reliable evidence of antibodies to swine influenza viruses among persons occupationally exposed to pigs. Most avian influenza studies target H5, H7 and H9 subtypes and most serological evidence of human exposure to avian influenza viruses is reported for these subtypes. Avian influenza studies receiving a low grade in this review often reported higher seroprevalences in humans compared with studies with a high grade. Official surveillance systems mainly focus on avian H5 and H7 viruses. Swine influenza viruses and avian subtypes other than H5 and H7 (emphasising H9) should be additionally included in official surveillance systems. Surveillance efforts should also be directed towards understudied geographical areas, such as Africa and South America. PMID:27874827

  5. Ultraviolet-C irradiation for inactivation of viruses in foetal bovine serum.

    Science.gov (United States)

    Vaidya, Vivek; Dhere, Rajeev; Agnihotri, Snehal; Muley, Ravindra; Patil, Sanjay; Pawar, Amit

    2018-07-05

    Foetal Bovine Serum (FBS) and porcine trypsin are one of the essential raw materials used in the manufacturing of cell culture based viral vaccines. Being from animal origin, these raw materials can potentially contaminate the final product by known or unknown adventitious agents. The issue is more serious in case of live attenuated viral vaccines, where there is no inactivation step which can take care of such adventitious agents. It is essential to design production processes which can offer maximum viral clearance potential for animal origin products. Ultraviolet-C irradiation is known to inactivate various adventitious viral agents; however there are limited studies on ultraviolet inactivation of viruses in liquid media. We obtained a recently developed UVivatec ultraviolet-C (UV-C) irradiation based viral clearance system for evaluating its efficacy to inactivate selected model viruses. This system has a unique design with spiral path of liquid allowing maximum exposure to UV-C light of a short wavelength of 254 nm. Five live attenuated vaccine viruses and four other model viruses were spiked in tissue culture media and exposed to UV-C irradiation. The pre and post UV-C irradiation samples were analyzed for virus content to find out the extent of inactivation of various viruses. These experiments showed substantial log reduction for the majority of the viruses with few exceptions based on the characteristics of these viruses. Having known the effect of UV irradiation on protein structure, we also evaluated the post irradiation samples of culture media for growth promoting properties using one of the most fastidious human diploid cells (MRC-5). UV-C exposure did not show any notable impact on the nutritional properties of culture media. The use of an UV-C irradiation based system is considered to be promising approach to mitigate the risk of adventitious agents in cell culture media arising through animal derived products. Copyright © 2018 Elsevier Ltd. All

  6. Swine influenza viruses isolated in 1983, 2002 and 2009 in Sweden exemplify different lineages

    Directory of Open Access Journals (Sweden)

    Metreveli Giorgi

    2010-12-01

    Full Text Available Abstract Swine influenza virus isolates originating from outbreaks in Sweden from 1983, 2002 and 2009 were subjected to nucleotide sequencing and phylogenetic analysis. The aim of the studies was to obtain an overview on their potential relatedness as well as to provide data for broader scale studies on swine influenza epidemiology. Nonetheless, analyzing archive isolates is justified by the efforts directed to the comprehension of the appearance of pandemic H1N1 influenza virus. Interestingly, this study illustrates the evolution of swine influenza viruses in Europe, because the earliest isolate belonged to 'classical' swine H1N1, the subsequent ones to Eurasian 'avian-like' swine H1N1 and reassortant 'avian-like' swine H1N2 lineages, respectively. The latter two showed close genetic relatedness regarding their PB2, HA, NP, and NS genes, suggesting common ancestry. The study substantiates the importance of molecular surveillance for swine influenza viruses.

  7. Prevalence of influenza virus among the paediatric population in Mumbai during 2007-2009.

    Science.gov (United States)

    Roy, S; Patil, D; Dahake, R; Mukherjee, S; Athlekar, S V; Deshmukh, R A; Chowdhary, A

    2012-01-01

    Influenza has a major impact on public heath, annually affecting 15-20% of the global population. Information on the activity of influenza virus in Mumbai is limited. The present study was carried out to determine the prevalence of influenza viruses causing acute respiratory infections in children by molecular methods. To study the prevalence of influenza viruses among the paediatric population in Mumbai by real-time reverse-transcriptase polymerase chain reaction (rRT-PCR). From July 2007 to July 2009, 100 respiratory samples (nasal and throat swabs) were collected from paediatric patients with acute respiratory symptoms. attending out patients department, and admitted to the paediatric wards of B. J. Wadia Hospital for Children, Mumbai. The samples were collected and processed as per World Health Organization (WHO) guidelines. Viral RNA was extracted and one-step rRT-PCR was performed to detect influenza type A (H1 and H3) and influenza type B virus. Out of 100 samples processed by rRT-PCR, a total of 11 samples (11%) were positive for influenza virus. The typing for influenza A subtypes showed 1% (1) positivity for H1 and 5% (5) positivity for H3 subtypes and 5% (5) samples tested positive for influenza type B virus. It was observed that both influenza type A and B viruses were prevalent in Mumbai during the study period. Such surveillance data are important in the early detection of any antigenic variants that may be helpful in global influenza vaccine preparation and for any pandemic preparedness activity.

  8. Replication of avian influenza viruses in equine tracheal epithelium but not in horses

    OpenAIRE

    Chambers, Thomas M.; Balasuriya, Udeni B. R.; Reedy, Stephanie E.; Tiwari, Ashish

    2013-01-01

    We evaluated a hypothesis that horses are susceptible to avian influenza viruses by in vitro testing, using explanted equine tracheal epithelial cultures, and in vivo testing by aerosol inoculation of ponies. Results showed that several subtypes of avian influenza viruses detectably replicated in vitro. Three viruses with high in vitro replication competence were administered to ponies. None of the three demonstrably replicated or caused disease signs in ponies. While these results do not exh...

  9. Inefficient Transmission of H5N1 Influenza Viruses in a Ferret Contact Model▿

    OpenAIRE

    Yen, Hui-Ling; Lipatov, Aleksandr S.; Ilyushina, Natalia A.; Govorkova, Elena A.; Franks, John; Yilmaz, Neziha; Douglas, Alan; Hay, Alan; Krauss, Scott; Rehg, Jerold E.; Hoffmann, Erich; Webster, Robert G.

    2007-01-01

    The abilities to infect and transmit efficiently among humans are essential for a novel influenza A virus to cause a pandemic. To evaluate the pandemic potential of widely disseminated H5N1 influenza viruses, a ferret contact model using experimental groups comprised of one inoculated ferret and two contact ferrets was used to study the transmissibility of four human H5N1 viruses isolated from 2003 to 2006. The effects of viral pathogenicity and receptor binding specificity (affinity to synth...

  10. No evidence that migratory geese disperse avian influenza viruses from breeding to wintering ground

    OpenAIRE

    Yin, Shenglai; Kleijn, David; M?skens, Gerard J. D. M.; Fouchier, Ron A. M.; Verhagen, Josanne H.; Glazov, Petr M.; Si, Yali; Prins, Herbert H. T.; de Boer, Willem Frederik

    2017-01-01

    textabstractLow pathogenic avian influenza virus can mutate to a highly pathogenic strain that causes severe clinical signs in birds and humans. Migratory waterfowl, especially ducks, are considered the main hosts of low pathogenic avian influenza virus, but the role of geese in dispersing the virus over long-distances is still unclear. We collected throat and cloaca samples from three goose species, Bean goose (Anser fabalis), Barnacle goose (Branta leucopsis) and Greater white-fronted goose...

  11. Predicting Zoonotic Risk of Influenza A Viruses from Host Tropism Protein Signature Using Random Forest

    OpenAIRE

    Christine L. P. Eng; Joo Chuan Tong; Tin Wee Tan

    2017-01-01

    Influenza A viruses remain a significant health problem, especially when a novel subtype emerges from the avian population to cause severe outbreaks in humans. Zoonotic viruses arise from the animal population as a result of mutations and reassortments, giving rise to novel strains with the capability to evade the host species barrier and cause human infections. Despite progress in understanding interspecies transmission of influenza viruses, we are no closer to predicting zoonotic strains th...

  12. Reassortment and evolution of current human influenza A and B viruses.

    Science.gov (United States)

    Xu, Xiyan; Lindstrom, Stephen E; Shaw, Michael W; Smith, Catherine B; Hall, Henrietta E; Mungall, Bruce A; Subbarao, Kanta; Cox, Nancy J; Klimov, Alexander

    2004-07-01

    During the 2001-2002 influenza season, human influenza A (H1N2) reassortant viruses were detected globally. The hemagglutinin (HA) of these H1N2 viruses was similar to that of the A/New Caledonia/20/99 (H1N1) vaccine strain both antigenically and genetically, while their neuraminidase (NA) was antigenically and genetically related to that of recent human influenza H3N2 reference viruses such as A/Moscow/10/99. All six internal genes of the H1N2 reassortants originated from an H3N2 virus. After being detected only in eastern Asia during the past 10 years, Influenza B/Victoria/2/87 lineage viruses reappeared in many countries outside of Asia in 2001. Additionally, reassortant influenza B viruses possessing an HA similar to that of B/Shandong/7/97, a recent B/Victoria/2/87 lineage reference strain, and an NA closely related to that of B/Sichuan/379/99, a recent B/Yamagata/16/88 lineage reference strain, were isolated globally and became the predominant influenza B epidemic strain. The current influenza vaccine is expected to provide good protection against H1N2 viruses because it contains A/New Caledonia/20/99 (H1N1) and A/Panama/2007/99 (H3N2) like viruses whose H1 HA or N2 NA are antigenically similar to those of recent circulating H1N2 viruses. On the other hand, widespread circulation of influenza B Victoria lineage viruses required inclusion of a strain from this lineage in influenza vaccines for the 2002-2003 season.

  13. Influenza A(H10N7) Virus in Dead Harbor Seals, Denmark

    DEFF Research Database (Denmark)

    Krog, Jesper Schak; Hansen, Mette Sif; Holm, Elisabeth

    2015-01-01

    Since April 2014, an outbreak of influenza in harbor seals has been ongoing in northern Europe. In Denmark during June-August, 152 harbor seals on the island of Anholt were found dead from severe pneumonia. We detected influenza A(H10N7) virus in 2 of 4 seals examined.......Since April 2014, an outbreak of influenza in harbor seals has been ongoing in northern Europe. In Denmark during June-August, 152 harbor seals on the island of Anholt were found dead from severe pneumonia. We detected influenza A(H10N7) virus in 2 of 4 seals examined....

  14. Prevalence and control of H7 avian influenza viruses in birds and humans.

    Science.gov (United States)

    Abdelwhab, E M; Veits, J; Mettenleiter, T C

    2014-05-01

    The H7 subtype HA gene has been found in combination with all nine NA subtype genes. Most exhibit low pathogenicity and only rarely high pathogenicity in poultry (and humans). During the past few years infections of poultry and humans with H7 subtypes have increased markedly. This review summarizes the emergence of avian influenza virus H7 subtypes in birds and humans, and the possibilities of its control in poultry. All H7Nx combinations were reported from wild birds, the natural reservoir of the virus. Geographically, the most prevalent subtype is H7N7, which is endemic in wild birds in Europe and was frequently reported in domestic poultry, whereas subtype H7N3 is mostly isolated from the Americas. In humans, mild to fatal infections were caused by subtypes H7N2, H7N3, H7N7 and H7N9. While infections of humans have been associated mostly with exposure to domestic poultry, infections of poultry have been linked to wild birds or live-bird markets. Generally, depopulation of infected poultry was the main control tool; however, inactivated vaccines were also used. In contrast to recent cases caused by subtype H7N9, human infections were usually self-limiting and rarely required antiviral medication. Close genetic and antigenic relatedness of H7 viruses of different origins may be helpful in development of universal vaccines and diagnostics for both animals and humans. Due to the wide spread of H7 viruses and their zoonotic importance more research is required to better understand the epidemiology, pathobiology and virulence determinants of these viruses and to develop improved control tools.

  15. Evaluation of the Cepheid Xpert Flu Assay for rapid identification and differentiation of influenza A, influenza A 2009 H1N1, and influenza B viruses.

    Science.gov (United States)

    Novak-Weekley, S M; Marlowe, E M; Poulter, M; Dwyer, D; Speers, D; Rawlinson, W; Baleriola, C; Robinson, C C

    2012-05-01

    The Xpert Flu Assay cartridge is a next-generation nucleic acid amplification system that provides multiplexed PCR detection of the influenza A, influenza A 2009 H1N1, and influenza B viruses in approximately 70 min with minimal hands-on time. Six laboratories participated in a clinical trial comparing the results of the new Cepheid Xpert Flu Assay to those of culture or real-time PCR with archived and prospectively collected nasal aspirate-wash (NA-W) specimens and nasopharyngeal (NP) swabs from children and adults. Discrepant results were resolved by DNA sequence analysis. After discrepant-result analysis, the sensitivities of the Xpert Flu Assay for prospective NA-W specimens containing the influenza A, influenza A 2009 H1N1, and influenza B viruses compared to those of culture were 90.0%, 100%, and 100%, respectively, while the sensitivities of the assay for prospective NP swabs compared to those of culture were 100%, 100%, and 100%, respectively. The sensitivities of the Xpert Flu Assay for archived NA-W specimens compared to those of Gen-Probe ProFlu+ PCR for the influenza A, influenza A 2009 H1N1, and influenza B viruses were 99.4%, 98.4%, and 100%, respectively, while the sensitivities of the Xpert Flu Assay for archived NP swabs compared to those of ProFlu+ were 98.1%, 100%, and 93.8%, respectively. The sensitivities of the Xpert Flu Assay with archived NP specimens compared to those of culture for the three targets were 97.5%, 100%, and 93.8%, respectively. We conclude that the Cepheid Xpert Flu Assay is an accurate and rapid method that is suitable for on-demand testing for influenza viral infection.

  16. Development of an influenza virus vaccine using the baculovirus-insect cell expression system : implications for pandemic preparedness

    NARCIS (Netherlands)

    Cox, M.M.J.

    2009-01-01

    Key word

    Influenza, rHA, vaccine, baculovirus, insect cells, production, pandemic preparedness

    Influenza (or flu) is a highly contagious, acute viral respiratory disease that occurs seasonally in most parts of the world and is caused by influenza viruses. Influenza

  17. Surveillance and identification of influenza A viruses in wild aquatic birds in the Crimea, Ukraine (2006-2008)

    Science.gov (United States)

    The ecology of avian influenza (AI) viruses in wild aquatic birds of Asia is poorly understood. From March 2006 through November 2008, 20 avian influenza viruses were isolated in the Crimea region of Ukraine, with an overall virus isolation frequency of 3.3%. All the viruses were isolated from thr...

  18. Genetic analysis of influenza B viruses isolated in Uganda during the 2009–2010 seasons

    Directory of Open Access Journals (Sweden)

    Byarugaba Denis K

    2013-01-01

    Full Text Available Abstract Background Influenza B viruses can cause morbidity and mortality in humans but due to the lack of an animal reservoir are not associated with pandemics. Because of this, there is relatively limited genetic sequences available for influenza B viruses, especially from developing countries. Complete genome analysis of one influenza B virus and several gene segments of other influenza B viruses isolated from Uganda from May 2009 through December 2010 was therefore undertaken in this study. Methods Samples were collected from patients showing influenza like illness and screened for influenza A and B by PCR. Influenza B viruses were isolated on Madin-Darby Canine Kidney cells and selected isolates were subsequently sequenced and analyzed phylogenetically. Findings Of the 2,089 samples collected during the period, 292 were positive by PCR for influenza A or B; 12.3% of the PCR positives were influenza B. Thirty influenza B viruses were recovered and of these 25 that grew well consistently on subculture were subjected to further analysis. All the isolates belonged to the B/Victoria-lineage as identified by hemagglutination inhibition assay and genetic analysis except one isolate that grouped with the B-Yamagata-lineage. The Ugandan B/Victoria-lineage isolates grouped in clade 1 which was defined by the N75K, N165K and S172P substitutions in hemagglutinin (HA protein clustered together with the B/Brisbane/60/2008 vaccine strain. The Yamagata-like Ugandan strain, B/Uganda/MUWRP-053/2009, clustered with clade 3 Yamagata viruses such as B/Bangladesh/3333/2007 which is characterized by S150I and N166Y substitutions in HA. Conclusion In general there was limited variation among the Ugandan isolates but they were interestingly closer to viruses from West and North Africa than from neighboring Kenya. Our isolates closely matched the World Health Organization recommended vaccines for the seasons.

  19. A Review of the Antiviral Susceptibility of Human and Avian Influenza Viruses over the Last Decade

    Science.gov (United States)

    Oh, Ding Yuan; Hurt, Aeron C.

    2014-01-01

    Antivirals play an important role in the prevention and treatment of influenza infections, particularly in high-risk or severely ill patients. Two classes of influenza antivirals have been available in many countries over the last decade (2004–2013), the adamantanes and the neuraminidase inhibitors (NAIs). During this period, widespread adamantane resistance has developed in circulating influenza viruses rendering these drugs useless, resulting in the reliance on the most widely available NAI, oseltamivir. However, the emergence of oseltamivir-resistant seasonal A(H1N1) viruses in 2008 demonstrated that NAI-resistant viruses could also emerge and spread globally in a similar manner to that seen for adamantane-resistant viruses. Previously, it was believed that NAI-resistant viruses had compromised replication and/or transmission. Fortunately, in 2013, the majority of circulating human influenza viruses remain sensitive to all of the NAIs, but significant work by our laboratory and others is now underway to understand what enables NAI-resistant viruses to retain the capacity to replicate and transmit. In this review, we describe how the susceptibility of circulating human and avian influenza viruses has changed over the last ten years and describe some research studies that aim to understand how NAI-resistant human and avian influenza viruses may emerge in the future. PMID:24800107

  20. Structural and Functional Motifs in Influenza Virus RNAs

    Directory of Open Access Journals (Sweden)

    Damien Ferhadian

    2018-03-01

    Full Text Available Influenza A viruses (IAV are responsible for recurrent influenza epidemics and occasional devastating pandemics in humans and animals. They belong to the Orthomyxoviridae family and their genome consists of eight (- sense viral RNA (vRNA segments of different lengths coding for at least 11 viral proteins. A heterotrimeric polymerase complex is bound to the promoter consisting of the 13 5′-terminal and 12 3′-terminal nucleotides of each vRNA, while internal parts of the vRNAs are associated with multiple copies of the viral nucleoprotein (NP, thus forming ribonucleoproteins (vRNP. Transcription and replication of vRNAs result in viral mRNAs (vmRNAs and complementary RNAs (cRNAs, respectively. Complementary RNAs are the exact positive copies of vRNAs; they also form ribonucleoproteins (cRNPs and are intermediate templates in the vRNA amplification process. On the contrary, vmRNAs have a 5′ cap snatched from cellular mRNAs and a 3′ polyA tail, both gained by the viral polymerase complex. Hence, unlike vRNAs and cRNAs, vmRNAs do not have a terminal promoter able to recruit the viral polymerase. Furthermore, synthesis of at least two viral proteins requires vmRNA splicing. Except for extensive analysis of the viral promoter structure and function and a few, mostly bioinformatics, studies addressing the vRNA and vmRNA structure, structural studies of the influenza A vRNAs, cRNAs, and vmRNAs are still in their infancy. The recent crystal structures of the influenza polymerase heterotrimeric complex drastically improved our understanding of the replication and transcription processes. The vRNA structure has been mainly studied in vitro using RNA probing, but its structure has been very recently studied within native vRNPs using crosslinking and RNA probing coupled to next generation RNA sequencing. Concerning vmRNAs, most studies focused on the segment M and NS splice sites and several structures initially predicted by bioinformatics analysis

  1. Vaccination of harbour seals (Phoca vitulina) against phocid distemper with two different inactivated canine distemper virus (CDV) vaccines.

    NARCIS (Netherlands)

    I.K.G. Visser (Ilona); M.W.G. van de Bildt (Marco); H.N. Brugge; P.J.H. Reijnders; E.J. Vedder (Lies); J. Kuiper; P. de Vries (Petra); J. Groen (Jan); H.C. Walvoort; F.G.C.M. Uytdehaag (Fons); A.D.M.E. Osterhaus (Albert)

    1989-01-01

    textabstractTwo inactivated canine distemper virus (CDV) vaccines--an adjuvanted whole inactivated virus and a subunit ISCOM preparation--were tested for their ability to induce protective immunity in harbour seals (Phoca vitulina) against phocid distemper, a disease that recently killed greater

  2. Genome-wide evolutionary dynamics of influenza B viruses on a global scale.

    Directory of Open Access Journals (Sweden)

    Pinky Langat

    2017-12-01

    Full Text Available The global-scale epidemiology and genome-wide evolutionary dynamics of influenza B remain poorly understood compared with influenza A viruses. We compiled a spatio-temporally comprehensive dataset of influenza B viruses, comprising over 2,500 genomes sampled worldwide between 1987 and 2015, including 382 newly-sequenced genomes that fill substantial gaps in previous molecular surveillance studies. Our contributed data increase the number of available influenza B virus genomes in Europe, Africa and Central Asia, improving the global context to study influenza B viruses. We reveal Yamagata-lineage diversity results from co-circulation of two antigenically-distinct groups that also segregate genetically across the entire genome, without evidence of intra-lineage reassortment. In contrast, Victoria-lineage diversity stems from geographic segregation of different genetic clades, with variability in the degree of geographic spread among clades. Differences between the lineages are reflected in their antigenic dynamics, as Yamagata-lineage viruses show alternating dominance between antigenic groups, while Victoria-lineage viruses show antigenic drift of a single lineage. Structural mapping of amino acid substitutions on trunk branches of influenza B gene phylogenies further supports these antigenic differences and highlights two potential mechanisms of adaptation for polymerase activity. Our study provides new insights into the epidemiological and molecular processes shaping influenza B virus evolution globally.

  3. Genome-wide evolutionary dynamics of influenza B viruses on a global scale

    Science.gov (United States)

    Langat, Pinky; Bowden, Thomas A.; Edwards, Stephanie; Gall, Astrid; Rambaut, Andrew; Daniels, Rodney S.; Russell, Colin A.; Pybus, Oliver G.; McCauley, John

    2017-01-01

    The global-scale epidemiology and genome-wide evolutionary dynamics of influenza B remain poorly understood compared with influenza A viruses. We compiled a spatio-temporally comprehensive dataset of influenza B viruses, comprising over 2,500 genomes sampled worldwide between 1987 and 2015, including 382 newly-sequenced genomes that fill substantial gaps in previous molecular surveillance studies. Our contributed data increase the number of available influenza B virus genomes in Europe, Africa and Central Asia, improving the global context to study influenza B viruses. We reveal Yamagata-lineage diversity results from co-circulation of two antigenically-distinct groups that also segregate genetically across the entire genome, without evidence of intra-lineage reassortment. In contrast, Victoria-lineage diversity stems from geographic segregation of different genetic clades, with variability in the degree of geographic spread among clades. Differences between the lineages are reflected in their antigenic dynamics, as Yamagata-lineage viruses show alternating dominance between antigenic groups, while Victoria-lineage viruses show antigenic drift of a single lineage. Structural mapping of amino acid substitutions on trunk branches of influenza B gene phylogenies further supports these antigenic differences and highlights two potential mechanisms of adaptation for polymerase activity. Our study provides new insights into the epidemiological and molecular processes shaping influenza B virus evolution globally. PMID:29284042

  4. Avian and human influenza A virus receptors in trachea and lung of animals.

    Science.gov (United States)

    Thongratsakul, Sukanya; Suzuki, Yasuo; Hiramatsu, Hiroaki; Sakpuaram, Thavajchai; Sirinarumitr, Theerapol; Poolkhet, Chaithep; Moonjit, Pattra; Yodsheewan, Rungrueang; Songserm, Thaweesak

    2010-12-01

    Influenza A viruses are capable of crossing the specific barrier between human beings and animals resulting in interspecies transmission. The important factor of potential infectivity of influenza A viruses is the suitability of the receptor binding site of the host and viruses. The affinities of avian and human influenza virus to bind with the receptors and the distributions of receptors in animals are different. This study aims to investigate the anatomical distribution of avian and human influenza virus receptors using the double staining lectin histochemistry method. Double staining of lectin histochemistry was performed to identify both SA alpha2,3 Gal and SA alpha2,6 Gal receptors in trachea and lung tissue of dogs, cats, tigers, ferret, pigs, ducks and chickens. We have demonstrated that avian and human influenza virus receptors were abundantly present in trachea, bronchus and bronchiole, but in alveoli of dogs, cats and tigers showed SA alpha2,6 Gal only. Furthermore, endothelial cells in lung tissues showed presence of SA alpha2,3 Gal. The positive sites of both receptors in respiratory tract, especially in the trachea, suggest that all mammalian species studied can be infected with avian influenza virus. These findings suggested that dogs and cats in close contact with humans should be of greater concern as an intermediate host for avian influenza A in which there is the potential for viral adaptation and reassortment.

  5. Rapid detection and subtyping of human influenza A viruses and reassortants by pyrosequencing.

    Directory of Open Access Journals (Sweden)

    Yi-Mo Deng

    Full Text Available BACKGROUND: Given the continuing co-circulation of the 2009 H1N1 pandemic influenza A viruses with seasonal H3N2 viruses, rapid and reliable detection of newly emerging influenza reassortant viruses is important to enhance our influenza surveillance. METHODOLOGY/PRINCIPAL FINDINGS: A novel pyrosequencing assay was developed for the rapid identification and subtyping of potential human influenza A virus reassortants based on all eight gene segments of the virus. Except for HA and NA genes, one universal set of primers was used to amplify and subtype each of the six internal genes. With this method, all eight gene segments of 57 laboratory isolates and 17 original specimens of seasonal H1N1, H3N2 and 2009 H1N1 pandemic viruses were correctly matched with their corresponding subtypes. In addition, this method was shown to be capable of detecting reassortant viruses by correctly identifying the source of all 8 gene segments from three vaccine production reassortant viruses and three H1N2 viruses. CONCLUSIONS/SIGNIFICANCE: In summary, this pyrosequencing assay is a sensitive and specific procedure for screening large numbers of viruses for reassortment events amongst the commonly circulating human influenza A viruses, which is more rapid and cheaper than using conventional sequencing approaches.

  6. Rapid detection and subtyping of human influenza A viruses and reassortants by pyrosequencing.

    Science.gov (United States)

    Deng, Yi-Mo; Caldwell, Natalie; Barr, Ian G

    2011-01-01

    Given the continuing co-circulation of the 2009 H1N1 pandemic influenza A viruses with seasonal H3N2 viruses, rapid and reliable detection of newly emerging influenza reassortant viruses is important to enhance our influenza surveillance. A novel pyrosequencing assay was developed for the rapid identification and subtyping of potential human influenza A virus reassortants based on all eight gene segments of the virus. Except for HA and NA genes, one universal set of primers was used to amplify and subtype each of the six internal genes. With this method, all eight gene segments of 57 laboratory isolates and 17 original specimens of seasonal H1N1, H3N2 and 2009 H1N1 pandemic viruses were correctly matched with their corresponding subtypes. In addition, this method was shown to be capable of detecting reassortant viruses by correctly identifying the source of all 8 gene segments from three vaccine production reassortant viruses and three H1N2 viruses. In summary, this pyrosequencing assay is a sensitive and specific procedure for screening large numbers of viruses for reassortment events amongst the commonly circulating human influenza A viruses, which is more rapid and cheaper than using conventional sequencing approaches.

  7. Influenza A virus infections in marine mammals and terrestrial carnivores.

    Science.gov (United States)

    Harder, Timm C; Siebert, Ursula; Wohlsein, Peter; Vahlenkamp, Thomas

    2013-01-01

    Influenza A viruses (IAV), members of the Orthomyxoviridae, cover a wide host spectrum comprising a plethora of avian and, in comparison, a few mammalian species. The viral reservoir and gene pool are kept in metapopulations of aquatic wild birds. The mammalian-adapted IAVs originally arose by transspecies transmission from avian sources. In swine, horse and man, species-adapted IAV lineages circulate independently of the avian reservoir and cause predominantly respiratory disease of highly variable severity. Sporadic outbreaks of IAV infections associated with pneumonic clinical signs have repeatedly occurred in marine mammals (harbour seals [Phoca vitulina]) off the New England coast of the U.S.A. due to episodic transmission of avian IAV. However, no indigenous marine mammal IAV lineages are described. In contrast to marine mammals, avian- and equine-derived IAVs have formed stable circulating lineages in terrestrial carnivores: IAVs of subtype H3N2 and H3N8 are found in canine populations in South Korea, China, and the U.S.A. Experimental infections revealed that dogs and cats can be infected with an even wider range of avian IAVs. Cats, in particular, also proved susceptible to native infection with human pandemic H1N1 viruses and, according to serological data, may be vulnerable to infection with further human-adapted IAVs. Ferrets are susceptible to a variety of avian and mammalian IAVs and are an established animal model of human IAV infection. Thus, a potential role of pet cats, dogs and ferrets as mediators of avian-derived viruses to the human population does exist. A closer observation for influenza virus infections and transmissions at this animal-human interface is indicated.

  8. Prospective surveillance for influenza. virus in Chinese swine farms.

    Science.gov (United States)

    Anderson, Benjamin D; Ma, Mai-Juan; Wang, Guo-Lin; Bi, Zhen-Qiang; Lu, Bing; Wang, Xian-Jun; Wang, Chuang-Xin; Chen, Shan-Hui; Qian, Yan-Hua; Song, Shao-Xia; Li, Min; Zhao, Teng; Wu, Meng-Na; Borkenhagen, Laura K; Cao, Wu-Chun; Gray, Gregory C

    2018-05-16

    Pork production in China is rapidly increasing and swine production operations are expanding in size and number. However, the biosecurity measures necessary to prevent swine disease transmission, particularly influenza. viruses (IAV) that can be zoonotic, are often inadequate. Despite this risk, few studies have attempted to comprehensively study IAV ecology in swine production settings. Here, we present environmental and animal sampling data collected in the first year of an ongoing five-year prospective epidemiological study to assess IAV ecology as it relates to swine workers, their pigs, and the farm environment. From March 2015 to February 2016, we collected 396 each of environmental swab, water, bioaerosol, and fecal/slurry samples, as well as 3300 pig oral secretion samples from six farms in China. The specimens were tested with molecular assays for IAV. Of these, 46 (11.6%) environmental swab, 235 (7.1%) pig oral secretion, 23 (5.8%) water, 20 (5.1%) bioaerosol, and 19 (4.8%) fecal/slurry specimens were positive for influenza. by qRT-PCR. Risk factors for IAV detection among collected samples were identified using bivariate logistic regression. Overall, these first year data suggest that IAV is quite ubiquitous in the swine production environment and demonstrate an association between the different types of environmental sampling used. Given the mounting evidence that some of these viruses freely move between pigs and swine workers, and that mixing of these viruses can yield progeny viruses with pandemic potential, it seems imperative that routine surveillance for novel IAVs be conducted in commercial swine farms.

  9. IL-15 enhances cross-reactive antibody recall responses to seasonal H3 influenza viruses in vitro [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Junqiong Huang

    2017-11-01

    Full Text Available Background: Recently, several human monoclonal antibodies that target conserved epitopes on the stalk region of influenza hemagglutinin (HA have shown broad reactivity to influenza A subtypes. Also, vaccination with recombinant chimeric HA or stem fragments from H3 influenza viruses induce broad immune protection in mice and humans. However, it is unclear whether stalk-binding antibodies can be induced in human memory B cells by seasonal H3N2 viruses. Methods: In this study, we recruited 13 donors previously exposed to H3 viruses, the majority (12 of 13 of which had been immunized with seasonal influenza vaccines. We evaluated plasma baseline strain-specific and stalk-reactive anti-HA antibodies and B cell recall responses to inactivated H3N2 A/Victoria/361/2011 virus in vitro using a high throughput multiplex (mPlex-Flu assay. Results: Stalk-reactive IgG was detected in the plasma of 7 of the subjects. Inactivated H3 viral particles rapidly induced clade cross-reactive antibodies in B cell cultures derived from all 13 donors. In addition, H3 stalk-reactive antibodies were detected in culture supernatants from 7 of the 13 donors (53.8%.  H3 stalk-reactive antibodies were also induced by H1 and H7 subtypes. Interestingly, broadly cross-reactive antibody recall responses to H3 strains were also enhanced by stimulating B cells in vitro with CpG2006 ODN in the presence of IL-15. H3 stalk-reactive antibodies were detected in  CpG2006 ODN + IL-15 stimulated B cell cultures derived from 12 of the 13 donors (92.3%, with high levels detected in cultures from 7 of the 13 donors. Conclusions: Our results demonstrate that stalk-reactive antibody recall responses induced by seasonal H3 viruses and CpG2006 ODN can be enhanced by IL-15.

  10. Avian influenza A virus and Newcastle disease virus mono- and co-infections in birds

    Directory of Open Access Journals (Sweden)

    Iv. Zarkov

    2017-06-01

    Full Text Available The main features of avian influenza viruses (AIV and Newcastle disease virus (APMV-1, the possibilities for isolation and identification in laboratory conditions, methods of diagnostics, main hosts, clinical signs and virus shedding are reviewed in chronological order. The other part of the review explains the mechanisms and interactions in cases of co-infection of AIV and APMV-1, either between them or with other pathogens in various indicator systems – cell cultures, chick embryos or birds. The emphasis is placed on quantitative data on the virus present mainly in the first ten days following experimental infection of birds, the periods of virus carrier ship and shedding, clinical signs, pathological changes, diagnostic challenges

  11. Acute Respiratory Distress Syndrome Caused by Influenza B Virus Infection in a Patient with Diffuse Large B-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Silvio A. Ñamendys-Silva

    2011-01-01

    Full Text Available Influenza B virus infections are less common than infections caused by influenza A virus in critically ill patients, but similar mortality rates have been observed for both influenza types. Pneumonia caused by influenza B virus is uncommon and has been reported in pediatric patients and previously healthy adults. Critically ill patients with pneumonia caused by influenza virus may develop acute respiratory distress syndrome. We describe the clinical course of a critically ill patient with diffuse large B-cell lymphoma nongerminal center B-cell phenotype who developed acute respiratory distress syndrome caused by influenza B virus infection. This paper emphasizes the need to suspect influenza B virus infection in critically ill immunocompromised patients with progressive deterioration of cardiopulmonary function despite treatment with antibiotics. Early initiation of neuraminidase inhibitor and the implementation of guidelines for management of severe sepsis and septic shock should be considered.

  12. The role of genomics in tracking the evolution of influenza A virus.

    Directory of Open Access Journals (Sweden)

    Alice Carolyn McHardy

    2009-10-01

    Full Text Available Influenza A virus causes annual epidemics and occasional pandemics of short-term respiratory infections associated with considerable morbidity and mortality. The pandemics occur when new human-transmissible viruses that have the major surface protein of influenza A viruses from other host species are introduced into the human population. Between such rare events, the evolution of influenza is shaped by antigenic drift: the accumulation of mutations that result in changes in exposed regions of the viral surface proteins. Antigenic drift makes the virus less susceptible to immediate neutralization by the immune system in individuals who have had a previous influenza infection or vaccination. A biannual reevaluation of the vaccine composition is essential to maintain its effectiveness due to this immune escape. The study of influenza genomes is key to this endeavor, increasing our understanding of antigenic drift and enhancing the accuracy of vaccine strain selection. Recent large-scale genome sequencing and antigenic typing has considerably improved our understanding of influenza evolution: epidemics around the globe are seeded from a reservoir in East-Southeast Asia with year-round prevalence of influenza viruses; antigenically similar strains predominate in epidemics worldwide for several years before being replaced by a new antigenic cluster of strains. Future in-depth studies of the influenza reservoir, along with large-scale data mining of genomic resources and the integration of epidemiological, genomic, and antigenic data, should enhance our understanding of antigenic drift and improve the detection and control of antigenically novel emerging strains.

  13. Antiviral Efficacy of Verdinexor In Vivo in Two Animal Models of Influenza A Virus Infection

    Science.gov (United States)

    Perwitasari, Olivia; Johnson, Scott; Yan, Xiuzhen; Register, Emery; Crabtree, Jackelyn; Gabbard, Jon; Howerth, Elizabeth; Shacham, Sharon; Carlson, Robert; Tamir, Sharon; Tripp, Ralph A.

    2016-01-01

    Influenza A virus (IAV) causes seasonal epidemics of respiratory illness that can cause mild to severe illness and potentially death. Antiviral drugs are an important countermeasure against IAV; however, drug resistance has developed, thus new therapeutic approaches are being sought. Previously, we demonstrated the antiviral activity of a novel nuclear export inhibitor drug, verdinexor, to reduce influenza replication in vitro and pulmonary virus burden in mice. In this study, in vivo efficacy of verdinexor was further evaluated in two animal models or influenza virus infection, mice and ferrets. In mice, verdinexor was efficacious to limit virus shedding, reduce pulmonary pro-inflammatory cytokine expression, and moderate leukocyte infiltration into the bronchoalveolar space. Similarly, verdinexor-treated ferrets had reduced lung pathology, virus burden, and inflammatory cytokine expression in the nasal wash exudate. These findings support the anti-viral efficacy of verdinexor, and warrant its development as a novel antiviral therapeutic for influenza infection. PMID:27893810

  14. Antiviral Efficacy of Verdinexor In Vivo in Two Animal Models of Influenza A Virus Infection.

    Directory of Open Access Journals (Sweden)

    Olivia Perwitasari

    Full Text Available Influenza A virus (IAV causes seasonal epidemics of respiratory illness that can cause mild to severe illness and potentially death. Antiviral drugs are an important countermeasure against IAV; however, drug resistance has developed, thus new therapeutic approaches are being sought. Previously, we demonstrated the antiviral activity of a novel nuclear export inhibitor drug, verdinexor, to reduce influenza replication in vitro and pulmonary virus burden in mice. In this study, in vivo efficacy of verdinexor was further evaluated in two animal models or influenza virus infection, mice and ferrets. In mice, verdinexor was efficacious to limit virus shedding, reduce pulmonary pro-inflammatory cytokine expression, and moderate leukocyte infiltration into the bronchoalveolar space. Similarly, verdinexor-treated ferrets had reduced lung pathology, virus burden, and inflammatory cytokine expression in the nasal wash exudate. These findings support the anti-viral efficacy of verdinexor, and warrant its development as a novel antiviral therapeutic for influenza infection.

  15. Radix isatidis Polysaccharides Inhibit Influenza a Virus and Influenza A Virus-Induced Inflammation via Suppression of Host TLR3 Signaling In Vitro

    Directory of Open Access Journals (Sweden)

    Zhengtu Li

    2017-01-01

    Full Text Available Influenza remains one of the major epidemic diseases worldwide, and rapid virus replication and collateral lung tissue damage caused by excessive pro-inflammatory host immune cell responses lead to high mortality rates. Thus, novel therapeutic agents that control influenza A virus (IAV propagation and attenuate excessive pro-inflammatory responses are needed. Polysaccharide extract from Radix isatidis, a traditional Chinese herbal medicine, exerted potent anti-IAV activity against human seasonal influenza viruses (H1N1 and H3N2 and avian influenza viruses (H6N2 and H9N2 in vitro. The polysaccharides also significantly reduced the expression of pro-inflammatory cytokines (IL-6 and chemokines (IP-10, MIG, and CCL-5 stimulated by A/PR/8/34 (H1N1 at a range of doses (7.5 mg/mL, 15 mg/mL, and 30 mg/mL; however, they were only effective against progeny virus at a high dose. Similar activity was detected against inflammation induced by avian influenza virus H9N2. The polysaccharides strongly inhibited the protein expression of TLR-3 induced by PR8, suggesting that they impair the upregulation of pro-inflammatory factors induced by IAV by inhibiting activation of the TLR-3 signaling pathway. The polysaccharide extract from Radix isatidis root therefore has the potential to be used as an adjunct to antiviral therapy for the treatment of IAV infection.

  16. Transmission of influenza A viruses between pigs and people, Iowa, 2002-2004.

    Science.gov (United States)

    Terebuh, Pauline; Olsen, Christopher W; Wright, Jennifer; Klimov, Alexander; Karasin, Alexander; Todd, Karla; Zhou, Hong; Hall, Henrietta; Xu, Xiyan; Kniffen, Tim; Madsen, David; Garten, Rebecca; Bridges, Carolyn B

    2010-11-01

    Triple-reassortant (tr) viruses of human, avian, and swine origin, including H1N1, H1N2, and H3N2 subtypes, emerged in North American swine herds in 1998 and have become predominant. While sporadic human infections with classical influenza A (H1N1) and with tr-swine influenza viruses have been reported, relatively few have been documented in occupationally exposed swine workers (SW). We conducted a 2-year (2002-2004) prospective cohort study of transmission of influenza viruses between pigs and SW from a single pork production company in Iowa. Respiratory samples were collected and tested for influenza viruses from SW and from pigs under their care through surveillance for influenza-like illnesses (ILI). Serial blood samples from study participants were tested by hemagglutination inhibition (HI) for antibody seroconversion against human and swine influenza viruses (SIV), and antibody seroprevalence was compared to age-matched urban Iowa blood donors. During the first year, 15 of 88 SW had ILI and were sampled; all were culture-negative for influenza. During the second year, 11 of 76 SW had ILI and were sampled; one was culture-positive for a human seasonal H3N2 virus. Among 20 swine herd ILI outbreaks sampled, influenza A virus was detected by rRT-PCR from 17 with 11 trH1N1 and five trH3N2 virus isolates cultured. During both years, HI geometric mean titers were significantly higher among SW compared to blood donor controls for three SIV: classical swine Sw/WI/238/97 (H1N1), tr Sw/IN/9K035/99 (H1N2), and trSw/IA/H02NJ56371/02 (H1N1)] (P influenza viruses and were exposed to diverse influenza virus strains circulating in pigs. Influenza virus surveillance among pigs and SW should be encouraged to better understand cross-species transmission and diversity of influenza viruses at the human-swine interface. © 2010 Blackwell Publishing Ltd.

  17. The Influenza Virus and the 2009 H1N1 Outbreak

    Science.gov (United States)

    2016-04-08

    MDW/SGVU SUBJECT: Professional Presentation Approval 8 APR 2016 1. Your paper, entitled The Influenza Virus and the 2009 HlNl Outbreak presented at...L TO BE PUBLISHED OR PRESENTED The Influenza Virus and the 2009 H1N1 Outbreak 2. FUNDING RECEIVED FOR THIS STUDY? DYES [g] NO FUNDING SOURCE: I I...336:!. ~~ 2 C-; MARKE. COON. :vtajor. USAF Acting Chic!’. Civil I.aw The Influenza Virus and the 2009 H 1 N 1 Outbreak Thomas. F. Gibbons, Ph.D

  18. Strengthening the influenza vaccine virus selection and development process: Report of the 3rd WHO Informal Consultation for Improving Influenza Vaccine Virus Selection held at WHO headquarters, Geneva, Switzerland, 1-3 April 2014

    NARCIS (Netherlands)

    Ampofo, W.K.; Azziz-Baumgartner, E.; Bashir, U.; Cox, N.J.; Fasce, R.; Giovanni, M.; Grohmann, G.; Huang, S.; Katz, J.; Mironenko, A.; Mokhtari-Azad, T.; Sasono, P.M.; Rahman, M.; Sawanpanyalert, P.; Siqueira, M.; Waddell, A.L.; Waiboci, L.; Wood, J.; Zhang, W.; Ziegler, T.; Paget, W.J.; et al.,

    2015-01-01

    Despite long-recognized challenges and constraints associated with their updating and manufacture, influenza vaccines remain at the heart of public health preparedness and response efforts against both seasonal and potentially pandemic influenza viruses. Globally coordinated virological and

  19. The Annexin A1 Receptor FPR2 Regulates the Endosomal Export of Influenza Virus

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    Fryad Rahman

    2018-05-01

    Full Text Available The Formyl Peptide Receptor 2 (FPR2 is a novel promising target for the treatment of influenza. During viral infection, FPR2 is activated by annexinA1, which is present in the envelope of influenza viruses; this activation promotes virus replication. Here, we investigated whether blockage of FPR2 would affect the genome trafficking of influenza virus. We found that, upon infection and cell treatment with the specific FPR2 antagonist WRW4 or the anti-FPR2 monoclonal antibody, FN-1D6-AI, influenza viruses were blocked into endosomes. This effect was independent on the strain and was observed for H1N1 and H3N2 viruses. In addition, blocking FPR2signaling in alveolar lung A549 epithelial cells with the monoclonal anti-FPR2 antibody significantly inhibited virus replication. Altogether, these results show that FPR2signaling interferes with the endosomal trafficking of influenza viruses and provides, for the first time, the proof of concept that monoclonal antibodies directed against FPR2 inhibit virus replication. Antibodies-based therapeutics have emerged as attractive reagents in infectious diseases. Thus, this study suggests that the use of anti-FPR2 antibodies against influenza hold great promise for the future.

  20. Influenza Virus Induces Inflammatory Response in Mouse Primary Cortical Neurons with Limited Viral Replication

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    Gefei Wang

    2016-01-01

    Full Text Available Unlike stereotypical neurotropic viruses, influenza A viruses have been detected in the brain tissues of human and animal models. To investigate the interaction between neurons and influenza A viruses, mouse cortical neurons were isolated, infected with human H1N1 influenza virus, and then examined for the production of various inflammatory molecules involved in immune response. We found that replication of the influenza virus in neurons was limited, although early viral transcription was not affected. Virus-induced neuron viability decreased at 6 h postinfection (p.i. but increased at 24 h p.i. depending upon the viral strain. Virus-induced apoptosis and cytopathy in primary cortical neurons were not apparent at 24 h p.i. The mRNA levels of inflammatory cytokines, chemokines, and type I interferons were upregulated at 6 h and 24 h p.i. These results indicate that the influenza virus induces inflammatory response in mouse primary cortical neurons with limited viral replication. The cytokines released in viral infection-induced neuroinflammation might play critical roles in influenza encephalopathy, rather than in viral replication-induced cytopathy.

  1. Respiratory viruses in airline travellers with influenza symptoms: Results of an airport screening study.

    Science.gov (United States)

    Jennings, Lance C; Priest, Patricia C; Psutka, Rebecca A; Duncan, Alasdair R; Anderson, Trevor; Mahagamasekera, Patalee; Strathdee, Andrew; Baker, Michael G

    2015-06-01

    There is very little known about the prevalence and distribution of respiratory viruses, other than influenza, in international air travellers and whether symptom screening would aid in the prediction of which travellers are more likely to be infected with specific respiratory viruses. In this study, we investigate whether, the use of a respiratory symptom screening tool at the border would aid in predicting which travellers are more likely to be infected with specific respiratory viruses. Data were collected from travellers arriving at Christchurch International Airport, New Zealand, during the winter 2008, via a symptom questionnaire, temperature testing, and respiratory sampling. Respiratory viruses were detected in 342 (26.0%) of 1313 samples obtained from 2714 symptomatic travellers. The most frequently identified viruses were rhinoviruses (128), enteroviruses (77) and influenza B (48). The most frequently reported symptoms were stuffy or runny nose (60%), cough (47%), sore throat (27%) and sneezing (24%). Influenza B infections were associated with the highest number of symptoms (mean of 3.4) followed by rhinoviruses (mean of 2.2) and enteroviruses (mean of 1.9). The positive predictive value (PPV) of any symptom for any respiratory virus infection was low at 26%. The high prevalence of respiratory virus infections caused by viruses other than influenza in this study, many with overlapping symptotology to influenza, has important implications for any screening strategies for the prediction of influenza in airline travellers. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Synthetic protocells interact with viral nanomachinery and inactivate pathogenic human virus.

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    Matteo Porotto

    Full Text Available We present a new antiviral strategy and research tool that could be applied to a wide range of enveloped viruses that infect human beings via membrane fusion. We test this strategy on two emerging zoonotic henipaviruses that cause fatal encephalitis in humans, Nipah (NiV and Hendra (HeV viruses. In the new approach, artificial cell-like particles (protocells presenting membrane receptors in a biomimetic manner were developed and found to attract and inactivate henipavirus envelope glycoprotein pseudovirus particles, preventing infection. The protocells do not accumulate virus during the inactivation process. The use of protocells that interact with, but do not accumulate, viruses may provide significant advantages over current antiviral drugs, and this general approach may have wide potential for antiviral development.

  3. Physicochemical inactivation of Lassa, Ebola, and Marburg viruses and effect on clinical laboratory analyses

    International Nuclear Information System (INIS)

    Mitchell, S.W.; McCormick, J.B.

    1984-01-01

    Clinical specimens from patients infected with Lassa, Ebola, or Marburg virus may present a serious biohazard to laboratory workers. The authors have examined the effects of heat, alteration of pH, and gamma radiation on these viruses in human blood and on the electrolytes, enzymes, and coagulation factors measured in laboratory tests that are important in the care of an infected patient. Heating serum at 60 degrees C for 1 h reduced high titers of these viruses to noninfectious levels without altering the serum levels of glucose, blood urea nitrogen, and electrolytes. Dilution of blood in 3% acetic acid, diluent for a leukocyte count, inactivated all of these viruses. All of the methods tested for viral inactivation markedly altered certain serum proteins, making these methods unsuitable for samples that are to be tested for certain enzyme levels and coagulation factors

  4. Development of an inactivated candidate vaccine against Chandipura virus (Rhabdoviridae: Vesiculovirus).

    Science.gov (United States)

    Jadi, R S; Sudeep, A B; Barde, P V; Arankalle, V A; Mishra, A C

    2011-06-20

    A Vero cell based vaccine candidate against Chandipura (CHP) virus (Rhabdoviridae: Vesiculovirus), was developed and evaluated for immunogenicity in mice. Virus was purified by ultracentrifugation on 30% glycerol cushion followed by differential centrifugation on 10-60% sucrose gradient and inactivated with β-propio lactone at a concentration of 1:3500. The inactivated product was blended with aluminium phosphate (3%) and immunized 4-week-old Swiss albino mice. Neutralizing antibodies in the range of 1:10 to 160 and 1:80 to 1:320 was detected with 85% and 100% sero-conversion after 2nd and 3rd dose, respectively. All the immunized mice with antibody titer above 1:20 survived live virus challenge. The vaccine candidate has potential to be an efficient vaccine against CHP virus. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. Clinical and Immune Responses to Inactivated Influenza A(H1N1)pdm09 Vaccine in Children

    Science.gov (United States)

    Kotloff, Karen L.; Halasa, Natasha B.; Harrison, Christopher J.; Englund, Janet A.; Walter, Emmanuel B.; King, James C.; Creech, C. Buddy; Healy, Sara A.; Dolor, Rowena J.; Stephens, Ina; Edwards, Kathryn M.; Noah, Diana L.; Hill, Heather; Wolff, Mark

    2014-01-01

    Background As the influenza AH1N1 pandemic emerged in 2009, children were found to experience high morbidity and mortality and were prioritized for vaccination. This multicenter, randomized, double-blind, age-stratified trial assessed the safety and immunogenicity of inactivated influenza A(H1N1)pdm09 vaccine in healthy children aged 6 months to 17 years. Methods Children received two doses of approximately 15 μg or 30 μg hemagglutin antigen 21 days apart. Reactogenicity was assessed for 8 days after each dose, adverse events through day 42, and serious adverse events or new-onset chronic illnesses through day 201. Serum hemagglutination inhibition (HAI) titers were measured on days 0 (pre-vaccination), 8, 21, 29, and 42. Results A total of 583 children received the first dose and 571 received the second dose of vaccine. Vaccinations were generally well-tolerated and no related serious adverse events were observed. The 15 μg dosage elicited a seroprotective HAI (≥1:40) in 20%, 47%, and 93% of children in the 6-35 month, 3-9 year, and 10-17 year age strata 21 days after dose 1 and in 78%, 82%, and 98% of children 21 days after dose 2, respectively. The 30 μg vaccine dosage induced similar responses. Conclusions The inactivated influenza A(H1N1)pdm09 vaccine exhibited a favorable safety profile at both dosage levels. While a single 15 or 30 μg dose induced seroprotective antibody responses in most 10-17 year olds, younger children required 2 doses, even when receiving dosages 4-6 fold higher than recommended. Well-tolerated vaccines are needed that induce immunity after a single dose for use in young children during influenza pandemics. PMID:25222307

  6. Syrian Hamster as an Animal Model for the Study of Human Influenza Virus Infection.

    Science.gov (United States)

    Iwatsuki-Horimoto, Kiyoko; Nakajima, Noriko; Ichiko, Yurie; Sakai-Tagawa, Yuko; Noda, Takeshi; Hasegawa, Hideki; Kawaoka, Yoshihiro

    2018-02-15

    Ferrets and mice are frequently used as animal models for influenza research. However, ferrets are demanding in terms of housing space and handling, whereas mice are not naturally susceptible to infection with human influenza A or B viruses. Therefore, prior adaptation of human viruses is required for their use in mice. In addition, there are no mouse-adapted variants of the recent H3N2 viruses, because these viruses do not replicate well in mice. In this study, we investigated the susceptibility of Syrian hamsters to influenza viruses with a view to using the hamster model as an alternative to the mouse model. We found that hamsters are sensitive to influenza viruses, including the recent H3N2 viruses, without adaptation. Although the hamsters did not show weight loss or clinical signs of H3N2 virus infection, we observed pathogenic effects in the respiratory tracts of the infected animals. All of the H3N2 viruses tested replicated in the respiratory organs of the hamsters, and some of them were detected in the nasal washes of infected animals. Moreover, a 2009 pandemic (pdm09) virus and a seasonal H1N1 virus, as well as one of the two H3N2 viruses, but not a type B virus, were transmissible by the airborne route in these hamsters. Hamsters thus have the potential to be a small-animal model for the study of influenza virus infection, including studies of the pathogenicity of H3N2 viruses and other strains, as well as for use in H1N1 virus transmission studies. IMPORTANCE We found that Syrian hamsters are susceptible to human influenza viruses, including the recent H3N2 viruses, without adaptation. We also found that a pdm09 virus and a seasonal H1N1 virus, as well as one of the H3N2 viruses, but not a type B virus tested, are transmitted by the airborne route in these hamsters. Syrian hamsters thus have the potential to be used as a small-animal model for the study of human influenza viruses. Copyright © 2018 American Society for Microbiology.

  7. Avian influenza A virus subtype H5N2 in a red-lored Amazon parrot.

    Science.gov (United States)

    Hawkins, Michelle G; Crossley, Beate M; Osofsky, Anna; Webby, Richard J; Lee, Chang-Won; Suarez, David L; Hietala, Sharon K

    2006-01-15

    A 3-month-old red-lored Amazon parrot (Amazona autumnalis autumnalis) was evaluated for severe lethargy. Avian influenza virus hemagglutinin subtype H5N2 with low pathogenicity was characterized by virus isolation, real-time reverse transcriptase PCR assay, chicken intravenous pathogenicity index, and reference sera. The virus was also determined to be closely related to a virus lineage that had been reported only in Mexico and Central America. The chick was admitted to the hospital and placed in quarantine. Supportive care treatment was administered. Although detection of H5 avian influenza virus in birds in the United States typically results in euthanasia of infected birds, an alternative strategy with strict quarantine measures and repeated diagnostic testing was used. The chick recovered from the initial clinical signs after 4 days and was released from quarantine 9 weeks after initial evaluation after 2 consecutive negative virus isolation and real-time reverse transcriptase PCR assay results. To the authors' knowledge, this is the first report of H5N2 avian influenza A virus isolated from a psittacine bird and represents the first introduction of this virus into the United States, most likely by illegal importation of psittacine birds. Avian influenza A virus should be considered as a differential diagnosis for clinical signs of gastrointestinal tract disease in psittacine birds, especially in birds with an unknown history of origin. Although infection with avian influenza virus subtype H5 is reportable, destruction of birds is not always required.

  8. A reverse genetic analysis of human Influenza A virus H1N2

    OpenAIRE

    Anton, Aline

    2010-01-01

    Reassortment between influenza A viruses of different subtypes rarely appears. Even in a community where H1N1 and H3N2 viruses co-circulate, reassortment to produce persistent viruses of mixed gene segments does not readily occur. H1N2 viruses, that circulated between 2001-2003 were considered to have arisen through the reassortment of the two human influenza subtypes H1N1 and H3N2. Due to the fact they make such a rare appearance, H1N2 viruses used to have new characteristics compared to the...

  9. A novel single virus infection system reveals that influenza virus preferentially infects cells in g1 phase.

    Directory of Open Access Journals (Sweden)

    Ryuta Ueda

    Full Text Available BACKGROUND: Influenza virus attaches to sialic acid residues on the surface of host cells via the hemagglutinin (HA, a glycoprotein expressed on the viral envelope, and enters into the cytoplasm by receptor-mediated endocytosis. The viral genome is released and transported in to the nucleus, where transcription and replication take place. However, cellular factors affecting the influenza virus infection such as the cell cycle remain uncharacterized. METHODS/RESULTS: To resolve the influence of cell cycle on influenza virus infection, we performed a single-virus infection analysis using optical tweezers. Using this newly developed single-virus infection system, the fluorescence-labeled influenza virus was trapped on a microchip using a laser (1064 nm at 0.6 W, transported, and released onto individual H292 human lung epithelial cells. Interestingly, the influenza virus attached selectively to cells in the G1-phase. To clarify the molecular differences between cells in G1- and S/G2/M-phase, we performed several physical and chemical assays. Results indicated that: 1 the membranes of cells in G1-phase contained greater amounts of sialic acids (glycoproteins than the membranes of cells in S/G2/M-phase; 2 the membrane stiffness of cells in S/G2/M-phase is more rigid than those in G1-phase by measurement using optical tweezers; and 3 S/G2/M-phase cells contained higher content of Gb3, Gb4 and GlcCer than G1-phase cells by an assay for lipid composition. CONCLUSIONS: A novel single-virus infection system was developed to characterize the difference in influenza virus susceptibility between G1- and S/G2/M-phase cells. Differences in virus binding specificity were associated with alterations in the lipid composition, sialic acid content, and membrane stiffness. This single-virus infection system will be useful for studying the infection mechanisms of other viruses.

  10. Genetic Characterization of Influenza A (H1N1) Pandemic 2009 Virus Isolates from Mumbai.

    Science.gov (United States)

    Gohil, Devanshi; Kothari, Sweta; Shinde, Pramod; Meharunkar, Rhuta; Warke, Rajas; Chowdhary, Abhay; Deshmukh, Ranjana

    2017-08-01

    Pandemic influenza A (H1N1) 2009 virus was first detected in India in May 2009 which subsequently became endemic in many parts of the country. Influenza A viruses have the ability to evade the immune response through its ability of antigenic variations. The study aims to characterize influenza A (H1N1) pdm 09 viruses circulating in Mumbai during the pandemic and post-pandemic period. Nasopharyngeal swabs positive for influenza A (H1N1) pdm 09 viruses were inoculated on Madin-Darby canine kidney cell line for virus isolation. Molecular and phylogenetic analysis of influenza A (H1N1) pdm 09 isolates was conducted to understand the evolution and genetic diversity of the strains. Nucleotide and amino acid sequences of the HA gene of Mumbai isolates when compared to A/California/07/2009-vaccine strain revealed 14 specific amino acid differences located at the antigenic sites. Amino acid variations in HA and NA gene resulted in changes in the N-linked glycosylation motif which may lead to immune evasion. Phylogenetic analysis of the isolates revealed their evolutionary position with vaccine strain A/California/07/2009 but had undergone changes gradually. The findings in the present study confirm genetic variability of influenza viruses and highlight the importance of continuous surveillance during influenza outbreaks.

  11. A flow-through chromatography process for influenza A and B virus purification.