接种2009年H1N1甲型流感疫苗对宿主抗异源流感病毒抗体免疫水平的影响

发布时间：2018-02-27 06:21

本文关键词： H1N1 甲型流感病毒疫苗中和抗体交叉反应　出处：《复旦大学》2014年博士论文　论文类型：学位论文

【摘要】：2009年春夏之际,全球范围内暴发流行了一株由经典猪流感病毒和欧亚系禽样猪流感病毒重配后而形成的新型甲型流感病毒,即2009年H1N1甲型流感病毒。为了控制2009年H1N1甲型流感病毒的传播,以及减轻临床症状和降低病死率,各国家和地区分别大规模地在高危易感人群中接种了疫苗。但是同一时期内在不同国家和地区均存在人际间流行着的H1N1和H3N2等普通季节性流感病毒,还有能够感染人且可能会在人际间扩散传播的高致病性H5N1禽流感病毒。这些病毒株同样地威胁着公众的健康。当人群普遍暴露过2009年H1N1甲型流感病毒以后,会对宿主体内针对于那些抗原性相异的甲型流感病毒的体液免疫反应造成怎样的影响便成了人们所关心的一个问题。我们使用流感假病毒方法分析了23名2009年H1N1甲型流感病毒疫苗受试者体内针对其它甲型流感病毒株中和抗体反应的变化。我们发现单针的无佐剂、灭活裂解型2009年H1N1甲型流感病毒疫苗不仅可以诱导针对自身抗原的同源中和反应,而且可以增强能够交叉识别H1N1、H3N2等季节性流感病毒以及高致病性H5N1禽流感病毒的中和反应。我们还发现在疫苗受试者的基线血清中已经存在了可以抑制2009年H1N1甲型流感病毒的中和抗体活性。2009年H1N1甲型流感病毒疫苗在诱导阻碍自身血凝素致红血球凝集的抗体的同时,也增强了可以交叉中和其它病毒株的抗体水平。当我们从具有较高交叉反应活性的血清标本中去除掉免疫球蛋白G以后,其中所含有的交叉中和活性几乎完全消失。相反,2009年H1N1甲型流感病毒疫苗并不能在没有感染过流感病毒的小鼠体内诱导出这些可以交叉识别其它病毒株的中和抗体。我们的数据提示2009年H1N1甲型流感病毒的血凝素蛋白中存在着可以诱发交叉中和抗体的表位。既往多次暴露流感病毒在宿主体内已经预先形成了微量的具有交叉识别多种亚型甲型流感病毒的记忆型B细胞,通过接种2009年H1N1甲型流感病毒疫苗可以再次活化这些具有交叉识别能力的记忆型B细胞。不论是通过接种了疫苗,还是感染过病毒,暴露过2009年H1N1甲型流感病毒之后会改变宿主免疫系统对其它流感病毒株的免疫记忆的强度和格局。这些发现有助于了解感染流感病毒或是接种流感病毒疫苗后,宿主针对流感病毒的免疫记忆的进化过程。
[Abstract]:In the spring and summer of 2009, a new influenza A virus, which was recombined with classical swine flu virus and Eurasian avian swine flu virus, broke out worldwide. In order to control the spread of the H1N1 influenza A virus on 2009, as well as to reduce clinical symptoms and mortality, Each country and region has been vaccinated on a large scale among high-risk vulnerable populations. But during the same period, common seasonal influenza viruses, such as H1N1 and H3N2, are prevalent in different countries and regions. There is also the highly pathogenic H5N1 avian influenza virus, which can infect humans and can spread from person to person. These strains also pose a threat to public health. The effect on the humoral immune response of the host to the antigenicity of influenza A viruses has become an issue of concern. We used the influenza pseudoviral method to analyze 23 cases of 2009 H1N1. Changes in neutralizing antibody responses to other influenza A strains in subjects of influenza A vaccine. We found a single needle without adjuvant. Inactivated lytic H1N1 influenza A virus vaccine of 2009 can not only induce homologous neutralization reaction against its own antigen. The neutralization reaction of seasonal influenza viruses such as H1, H3N2 and highly pathogenic H5N1 avian influenza viruses was enhanced. We also found that the baseline serum of vaccine subjects had been found to inhibit H1N1 A in 2009. The neutralizing antibody activity of influenza virus. In 2009, the H1N1 influenza A vaccine induced antibodies that blocked the hemagglutination caused by self hemagglutinin. It also increases the level of antibodies that can cross over and other virus strains. When we remove immunoglobulin G from serum samples with high cross-reaction activity, By contrast, the H1N1 influenza A vaccine in 2009 could not induce neutralization in mice that had not been infected with the influenza virus, which could cross-identify other strains of the virus. Our data suggest that in 2009, the hemagglutinin protein of H1N1 influenza A virus has an epitope that can induce cross-neutralizing antibodies. Memory B cells that recognize a variety of subtypes of influenza A virus. These memory B cells with cross-recognition can be reactivated by inoculating the H1N1 influenza A virus vaccine on 2009, whether through vaccination or infection with the virus. Exposure to the H1N1 influenza A virus on 2009 changes the immune memory intensity and pattern of the host's immune system against other influenza strains. The evolution of host immune memory against influenza viruses.
【学位授予单位】：复旦大学
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R511.7

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