Identifying determinants of human immunity against influenza: a multiscale approach

项目摘要 季节性流感是一个重大的公共卫生问题，但尚不清楚为什么个人和人群会有所不同 在预防流感感染方面的作用。保护的基础因素可以在多个范围内发挥作用，并且 因此，要建立对保护的更完整的理解，需要一种在 群体、个体和分子水平。哪些因素会影响人群和个人患流感的风险 感染？个体对流感的抗体反应有多大不同？是什么因素推动了这些反应？ 不同？在这里，我建议确定过去感染、接种疫苗和抗原的相对影响。 高分辨率定量模拟确定个体和群体磁化率的研究进展 流行病学和免疫学数据。特别是，我的目标是确定过去的流感感染在 塑造不同年龄段的易感性，确定人类抗体反应的特定靶点 预防流感，并推断感染史、疫苗接种和表位免疫原性的相对重要性 关于抗体的特异性。这项工作将对我们预测未来流感感染的能力产生重大影响 并使我们能够针对风险最高的人群进行干预。这个项目的成功需要培训 在先进的计算和统计方法以及最先进的免疫学技术方面 芝加哥大学生态与进化系和医学系。这一跨学科和 协作培训环境将为更全面地了解 流感与人类免疫系统之间的相互作用。

Project Summary Seasonal influenza is a significant public health concern, yet it is not clear why individuals and populations differ in their protection against influenza infection. The factors underlying protection can act at multiple scales, and thus building a more complete understanding of protection requires an approach that integrates data at the population, individual, and molecular levels. What factors influence population and individual risk of influenza infection? How different are the antibody responses of individuals against influenza and what factors drive those differences? Here, I propose to identify the relative influence of past infection, vaccination, and antigenic evolution on determining both individual and population susceptibility by quantitatively modeling high-resolution epidemiological and immunological data. In particular, I aim to determine the role of past influenza infection in shaping the susceptibility of different age groups, identify the specific targets of the human antibody response against influenza, and infer the relative importance of infection history, vaccination, and epitope immunogenicity on antibody specificity. This work will have a significant impact on our ability to predict future influenza infection and allow us to target interventions toward the most at-risk populations. Success of this project requires training in advanced computational and statistical methods and state-of-the-art immunological techniques by members of the Departments of Ecology & Evolution and Medicine at the University of Chicago. This interdisciplinary and collaborative training environment will provide a strong foundation for gaining more complete understanding of the interactions between influenza and the human immune system.