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，它们不能防止共循环的错配菌株，而且， 重要的是，不能提供针对可能导致潜在破坏性大流行的抗原性变化的保护。 该提案调查了T细胞免疫在个体和群体水平上的作用， 广泛的保护，防止不同的流感病毒株。动物和人类研究表明，T细胞可以提供 超越毒株保护，导致更快的病毒清除，减少免疫病理学， 改善临床结果，从而改善诱导流感保护水平的策略， 特异性T细胞至关重要。然而，人们对提高流感特异性抗体的规则知之甚少。 呼吸道中的常驻记忆T细胞面对先前流感的预先存在的体液免疫 感染或接种疫苗。我们将使用多尺度免疫流行病学方法， 在面对预先存在的疾病时， 免疫力和感染在人群中的传播。从这项研究中获得的知识将有助于 指导未来针对流感病毒的疫苗接种工作，以更好地产生广泛的保护性T细胞免疫 在个人和整个人群中。

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.