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      Protective efficacy of a high-growth reassortant swine H3N2 inactivated vaccine constructed by reverse genetic manipulation

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          Abstract

          Novel reassortant H3N2 swine influenza viruses (SwIV) with the matrix gene from the 2009 H1N1 pandemic virus have been isolated in many countries as well as during outbreaks in multiple states in the United States, indicating that H3N2 SwIV might be a potential threat to public health. Since southern China is the world's largest producer of pigs, efficient vaccines should be developed to prevent pigs from acquiring H3N2 subtype SwIV infections, and thus limit the possibility of SwIV infection at agricultural fairs. In this study, a high-growth reassortant virus (GD/PR8) was generated by plasmid-based reverse genetics and tested as a candidate inactivated vaccine. The protective efficacy of this vaccine was evaluated in mice by challenging them with another H3N2 SwIV isolate [A/Swine/Heilongjiang/1/05 (H3N2) (HLJ/05)]. Prime and booster inoculation with GD/PR8 vaccine yielded high-titer serum hemagglutination inhibiting antibodies and IgG antibodies. Complete protection of mice against H3N2 SwIV was observed, with significantly reduced lung lesion and viral loads in vaccine-inoculated mice relative to mock-vaccinated controls. These results suggest that the GD/PR8 vaccine may serve as a promising candidate for rapid intervention of H3N2 SwIV outbreaks in China.

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          Cross-reactive antibody responses to the 2009 pandemic H1N1 influenza virus.

          A new pandemic influenza A (H1N1) virus has emerged, causing illness globally, primarily in younger age groups. To assess the level of preexisting immunity in humans and to evaluate seasonal vaccine strategies, we measured the antibody response to the pandemic virus resulting from previous influenza infection or vaccination in different age groups. Using a microneutralization assay, we measured cross-reactive antibodies to pandemic H1N1 virus (2009 H1N1) in stored serum samples from persons who either donated blood or were vaccinated with recent seasonal or 1976 swine influenza vaccines. A total of 4 of 107 persons (4%) who were born after 1980 had preexisting cross-reactive antibody titers of 40 or more against 2009 H1N1, whereas 39 of 115 persons (34%) born before 1950 had titers of 80 or more. Vaccination with seasonal trivalent inactivated influenza vaccines resulted in an increase in the level of cross-reactive antibody to 2009 H1N1 by a factor of four or more in none of 55 children between the ages of 6 months and 9 years, in 12 to 22% of 231 adults between the ages of 18 and 64 years, and in 5% or less of 113 adults 60 years of age or older. Seasonal vaccines that were formulated with adjuvant did not further enhance cross-reactive antibody responses. Vaccination with the A/New Jersey/1976 swine influenza vaccine substantially boosted cross-reactive antibodies to 2009 H1N1 in adults. Vaccination with recent seasonal nonadjuvanted or adjuvanted influenza vaccines induced little or no cross-reactive antibody response to 2009 H1N1 in any age group. Persons under the age of 30 years had little evidence of cross-reactive antibodies to the pandemic virus. However, a proportion of older adults had preexisting cross-reactive antibodies. 2009 Massachusetts Medical Society
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            Rescue of influenza A virus from recombinant DNA.

            We have rescued influenza A virus by transfection of 12 plasmids into Vero cells. The eight individual negative-sense genomic viral RNAs were transcribed from plasmids containing human RNA polymerase I promoter and hepatitis delta virus ribozyme sequences. The three influenza virus polymerase proteins and the nucleoprotein were expressed from protein expression plasmids. This plasmid-based reverse genetics technique facilitates the generation of recombinant influenza viruses containing specific mutations in their genes.
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              Origin and evolution of the 1918 "Spanish" influenza virus hemagglutinin gene.

              The "Spanish" influenza pandemic killed over 20 million people in 1918 and 1919, making it the worst infectious pandemic in history. Here, we report the complete sequence of the hemagglutinin (HA) gene of the 1918 virus. Influenza RNA for the analysis was isolated from a formalin-fixed, paraffin-embedded lung tissue sample prepared during the autopsy of a victim of the influenza pandemic in 1918. Influenza RNA was also isolated from lung tissue samples from two additional victims of the lethal 1918 influenza: one formalin-fixed, paraffin-embedded sample and one frozen sample obtained by in situ biopsy of the lung of a victim buried in permafrost since 1918. The complete coding sequence of the A/South Carolina/1/18 HA gene was obtained. The HA1 domain sequence was confirmed by using the two additional isolates (A/New York/1/18 and A/Brevig Mission/1/18). The sequences show little variation. Phylogenetic analyses suggest that the 1918 virus HA gene, although more closely related to avian strains than any other mammalian sequence, is mammalian and may have been adapting in humans before 1918.
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                Author and article information

                Journal
                J Vet Sci
                J. Vet. Sci
                JVS
                Journal of Veterinary Science
                The Korean Society of Veterinary Science
                1229-845X
                1976-555X
                September 2014
                16 September 2014
                : 15
                : 3
                : 381-388
                Affiliations
                Division of Swine Infectious Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China.
                Author notes
                Corresponding authors: Tel: +86-21-34293436; Fax: +86-21-54081818; haiyu@ 123456shvri.ac.cn , gztong@ 123456shvri.ac.cn

                The first two authors contributed equally to this work.

                Article
                10.4142/jvs.2014.15.3.381
                4178139
                24675833
                4ef44ec7-5033-4620-90a2-f6b159faa394
                © 2014 The Korean Society of Veterinary Science.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 22 August 2013
                : 16 December 2013
                : 22 February 2014
                Funding
                Funded by: China International SCI & Tech Cooperation Program
                Award ID: 2010DFB33920
                Funded by: National Scientific Supporting Program of China
                Award ID: 2010BAD04B03
                Funded by: Chinese Research Fund for Non-profit Research Institutions
                Award ID: 2010JB02
                Funded by: Natural Science Foundation of Shanghai
                Award ID: 10JC1417300
                Funded by: National Natural Science Foundation of China
                Award ID: 31201916
                Funded by: Shanghai Natural Science Foundation of China
                Award ID: 12ZR1453500
                Categories
                Original Article

                Veterinary medicine
                h3n2 subtype,protective efficacy,reverse genetics,swine influenza virus
                Veterinary medicine
                h3n2 subtype, protective efficacy, reverse genetics, swine influenza virus

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