Prevention of influenza virus infection using ruminant polyclonal antibodies and the impact on the host immune response

    Research output: ThesisDoctoral Thesis

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    Abstract

    [Truncated] Emerging influenza viruses pose a serious global threat despite current vaccine technology, which has limited effectiveness during a pandemic due to inevitable delayed production and restrictive costs. A potential adjunct approach capable of alleviating this deficiency, whilst a strain-specific vaccine is produced, is passive immunisation using neutralising anti-influenza virus antibodies. A potential large scale production source of antibodies is large ruminants and with such ruminant polyclonal antibodies delivered via the intranasal route, to alleviate potential reactions to the heterologous protein and reduce antibody dose requirements due to delivery to the site of infection. Intranasal application of the antibodies would allow for neutralisation of the virus prior to entry to the cells of the respiratory tract. However, knowledge of the influence of these protective heterologous antibodies on development of the host immune response to the virus is limited.

    Influenza virus-specific antibodies were generated by inoculating sheep with influenza A/PR/8/34 virus antigen preparations. Purified influenza virus, which was subsequently detergent disrupted, produced the highest titres of neutralising antiinfluenza virus antibodies in both serum and whey. Several other antigen preparations, including inactivated virus culture supernatant and concentrated inactivated virus culture supernatant, produced low to moderate neutralising antibody titres, respectively, while rHA and DNA plasmid encoding the full length HA, were unsuccessful at producing significant anti-influenza virus specific antibody responses. Factors that influenced the antibody response to the antigens included concentration, purity and presence of influenza virus neutralising epitopes in the preparations.

    Protection experiments with a low neutralising anti-influenza virus specific antibody reduced clinical signs of influenza virus infection without reducing replicating virus levels on day 3 post-influenza virus infection. There were also no differences in cell infiltration, histopathology, innate cytokine and humoral immune responses to the virus in mice pre-treated with the low neutralising antibody compared to control mice. These antibodies were not considered appropriate for use in a pandemic as virus replication would; open the potential for virus mutation.

    Original languageEnglish
    QualificationDoctor of Philosophy
    Publication statusUnpublished - 2015

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