Pre-existing strain specific neutralising antibodies abrogates the induction of interferon type I and cytotoxic T cell responses to subsequent homotypic influenza A virus challenge.
| dc.contributor.advisor | Alsharifi, Mohammed | en |
| dc.contributor.advisor | McColl, Shaun Reuss | en |
| dc.contributor.author | Chan, Jennifer | en |
| dc.contributor.school | School of Molecular and Biomedical Science | en |
| dc.date.issued | 2013 | en |
| dc.description.abstract | Current inactivated influenza vaccines target the generation of influenza-specific antibodies to provide homotypic protection. However, little is known about the effects of annual vaccinations on the immune response during a subsequent influenza A virus infection. Here, we investigated the effect of pre-existing influenza-specific neutralising antibodies on innate and adaptive immunity during secondary infections. We report that the presence of pre-existing antibodies abrogates the induction of interferon type I (IFN-I) responses and cytotoxic T cell responses during subsequent influenza A virus infection. Wild-type mice were vaccinated intravenously with gamma-irradiated A/PR8 [H1N1] (γ-A/PR8) and challenged 3 weeks later with live A/PR8, and splenocytes were analysed 24 hours later for IFN-I mediated lymphocyte activation using fluorescent activated cell sorting. Our data clearly show absence of partial systemic lymphocyte activation and IFN-I responses in vaccinated mice. Furthermore, co-administration of A/PR8-specific sera and live A/PR8 virus abrogated the ability of live virus to induce partial lymphocyte activation, IFN-I responses as well as cytotoxic T cell responses. To test the clinical relevance of this observation, mice were mock or vaccinated with γ-A/PR8 and infected 3 weeks later with sub-lethal dose of A/PR8. These animals were then challenged 3 weeks later with lethal dose of A/PC [H3N2]. Our data clearly illustrate the effect of pre-existing antibodies on the ability of sub-lethal infection to generate cytotoxic T cell mediated heterosubtypic protection. I also investigated whether IFN-I responses are required for the generation of cytotoxic T cell responses in the presence of neutralising immune sera. My data show that addition of exogenous Poly I:C to A/PR8 virus pre-treated with A/PR8-specific sera did not rescue the induction of cytotoxic T cell responses. Thus, the presence of neutralising antibodies abrogates the induction of IFN-I and cytotoxic T cell responses during homotypic influenza A virus re-infection. | en |
| dc.description.dissertation | Thesis (M.Phil.) -- University of Adelaide, School of Molecular and Biomedical Science, 2013 | en |
| dc.identifier.uri | http://hdl.handle.net/2440/90751 | |
| dc.provenance | This electronic version is made publicly available by the University of Adelaide in accordance with its open access policy for student theses. Copyright in this thesis remains with the author. This thesis may incorporate third party material which has been used by the author pursuant to Fair Dealing exceptions. If you are the owner of any included third party copyright material you wish to be removed from this electronic version, please complete the take down form located at: http://www.adelaide.edu.au/legals | en |
| dc.subject | immune response; virus challenge; B cells; influenza A virus; T cells; antibodies; interferon type I | en |
| dc.title | Pre-existing strain specific neutralising antibodies abrogates the induction of interferon type I and cytotoxic T cell responses to subsequent homotypic influenza A virus challenge. | en |
| dc.type | Thesis | en |
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