Multiscale modeling of influenza vaccination strategies for optimal T cell immunity

项目摘要 目前的流感疫苗提供针对季节性流感病毒株的集中抗体介导的保护 包括在疫苗中。然而，它们不能防止共同循环的错配菌株，而且，更多 重要的是，未能针对可能导致潜在破坏性大流行的抗原转移提供保护。 这项建议调查了T细胞免疫在个体和群体水平上在提供 针对不同流感病毒株的广泛保护。动物和人类研究表明，T细胞可以提供 超越菌株的保护，导致更快的病毒清除，降低免疫病理学，以及 改善了临床结果，从而改进了诱导流感保护水平的策略- 特定的T细胞是至关重要的。然而，人们对提高流感特异性的规则知之甚少。 面对先前流感的体液免疫时呼吸道中的常驻记忆T细胞 感染或接种疫苗。我们将使用多尺度免疫流行病学方法，将来自 面对既往存在的疫苗接种，个体内感染和免疫的动态 免疫力和感染在人口层面的传播。从这项研究中获得的知识将有所帮助 指导未来针对流感病毒的疫苗接种工作，以更好地产生广泛保护性T细胞免疫 在个人内部和整个人口中。

Project Summary Current influenza vaccines provide focused antibody-mediated protection against seasonal influenza strains included in the vaccine. However, they do not protect from co-circulating mismatched strains, and, more importantly, fail to provide protection against antigenic shifts that can cause potentially devastating pandemics. This proposal investigates the role of T cell immunity, on both the individual and population levels, in providing broad protection against diverse influenza strains. Animal and human studies showed that T cells can provide strain-transcending protection, resulting in more rapid viral clearance, decreased immunopathology, and improved clinical outcomes, and thus the improvement of strategies to induce protective levels of influenza- specific T cells are of critical importance. However, little is known about the rules for boosting influenza-specific resident memory T cells in the respiratory tract in the face of pre-existing humoral immunity from prior influenza infections or vaccinations. We will use multi-scale immuno-epidemiological methods that link the scales from the dynamics of infection and immunity within individuals to take of vaccination in the face of pre-existing immunity and the spread of infection on the population level. The knowledge gained form this study will help guide future vaccination efforts against influenza viruses to better generate broadly protective T cell immunity within individuals and across the population.