2011-08-012024-05-14https://scholars.lib.ntu.edu.tw/handle/123456789/659614摘要：過去數十年來，過敏病病人數持續增加。過敏性氣喘是呼吸道發炎反應，其特徵為呼吸道出現嗜酸性白血球及TH2細胞。雖然流感病毒的感染是否造成氣喘尚未有定論，氣喘病童仍被建議應施打流感疫苗。但流感疫苗在過敏性氣喘之影響及疫苗效果則還不清楚。本研究將以OVA致敏之氣喘小鼠探討流感疫苗對過敏性氣喘之影響及疫苗之效果。4個子目標如下:1) 研究小鼠給予流感疫苗後產生抗病毒之免疫反應。我們將以皮下或肌肉內注射一次或多次的去活性流感病毒或市售流感疫苗予小鼠，測量其抗流感病毒之免疫反應。2) 研究流感疫苗是否加重或減緩過敏性氣喘。我們將給予OVA致敏小鼠流感疫苗後評估其過敏反應。除此之外，我們也將測量給予疫苗小鼠之iNKT細胞及調控型T細胞的比例及數目以探究其機轉。3) 研究流感疫苗在過敏性氣喘之效果。我們將給流感疫苗予OVA致敏小鼠，測量其抗流感免疫反應。此外，我們將感染注射過疫苗的OVA致敏小鼠後觀測其抗病毒效果。4) 研究給與-GalCer加強流感疫苗在過敏性氣喘之效果。我們將給予-GalCer與流感疫苗予OVA致敏小鼠，測量其抗流感病毒之免疫反應。我們將比較給予疫苗或疫苗及-GalCer的OVA致敏小鼠在流感病毒感染下之效果。本實驗將使我們了解鼓勵氣喘病人施打流感疫苗的政策是否合宜。<br> Abstract: Over the last few decades, the number of patients affected by allergic diseases in the whole world has considerably increased. Allergic asthma is associated with an inflammatory process characterized by the increased presence of eosinophils and TH2 cells in the airway. Infection with influenza virus has been associated with seemingly opposing effects on the development of asthma. While yearly influenza vaccination is widely recommended for children with asthma, there is still unknown the effects and efficacy of influenza vaccination on patients with asthma. In this study, we will evaluate the effect and efficacy of influenza vaccination on allergic asthma by using an OVA-immunized mouse model.Specific Aim 1. Determine the anti-influenza immune responses in mice with influenza vaccination. We will subcutaneously or intramuscularly inject naïve mice with a single dose or multiple doses of UV-inactivated PR8 influenza virus or commercial flu vaccine and measure the anti-influenza antibodies IgG1 and IgG2a, T cell proliferation, and cytokine production. These experiments will be able us to confirm the efficacy of influenza vaccination we use in mice.Specific Aim 2. Determine whether influenza vaccination improve or exacerbate the outcome of allergic asthma. We will give flu vaccine to OVA-immunized mice before or after OVA-immunization and measure the manifestations of allergic asthma including serum levels of OVA-specific IgE, airway function, cell infiltrates to lung, cytokines in bronchoalveolar lavage (BAL) of mice after OVA challenge. In addition, the frequencies of invariant natural killer T (iNKT) cells and regulatory T cells in spleen of vaccine-injected OVA-immunized and challenged mice will be measured to clarify the possible mechanism if influenza vaccination improve the outcome of allergic asthma. These experiments will be able us to clarify whether influenza vaccination improve or exacerbate the outcome of allergic asthma and how it works.Specific Aim 3. Determine the efficacy of influenza vaccination in mice with allergic asthma. We will inject OVA-immunized mice with UV-inactivated PR8 influenza virus or commercial flu vaccine and measure the anti-influenza antibodies IgG1 and IgG2a, T cell proliferation, CTL response, and cytokine secretion like the specific aim 1 do. In addition, we will challenge vaccinated mice with live influenza virus and measure the efficacy of vaccination on allergic mice. These experiments will be able us to understand whether there is any difference in the efficacy of influenza vaccination in allergic asthma and normal.Specific Aim 4. Determine whether coadministration of -GalCer enhances the efficacy of influenza vaccination in mice with allergic asthma. We will give flu vaccine in the presence with/without -GalCer to OVA-immunized mice and anti-influenza antibodies IgG1 and IgG2a, T cell proliferation, CTL response, and cytokine production of mice will be assayed. In addition, we will challenge vaccinated mice with live influenza virus and measure the efficacy of vaccination on allergic mice.This study will be able us to evaluate the strategy of influenza vaccination on allergic asthma.流感病毒氣喘IL-4IL-6TLR7PR8asthmaIL-4IL-6TLR7