Multiscale modeling of influenza vaccination strategies for optimal T cell immunity

流感疫苗接种策略的多尺度建模以实现最佳 T 细胞免疫

基本信息

批准号：
9766363
负责人：
JACOB E KOHLMEIER
金额：
$ 70.07万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-01 至 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9766363
关键词：
Affect Animals Antibody-mediated protection Antigens Attenuated CD8-Positive T-Lymphocytes Cell Count Cells Childhood Clinical Complex Development Effectiveness Epidemiologic Methods Epidemiology Epitopes Exhibits Exposure to Failure Feedback Future Hemagglutinin Herd Immunity Human Humoral Immunities Immune response Immunity Immunization Immunize Immunologic Memory Individual Infection Influenza Influenza vaccination Knowledge Link Longevity Lung Measles Memory Modeling Outcome Population Proteins Respiratory System Role Severities Surface T cell response T memory cell T-Lymphocyte Time Transcend Vaccinated Vaccination Vaccine Design Vaccines Variant Viral Virus Yellow Fever Vaccine base design and construction epidemiological model experience experimental study immunopathology improved influenza virus vaccine influenzavirus live attenuated influenza vaccine mathematical model multi-scale modeling pandemic disease pandemic influenza prevent seasonal influenza transmission process trivalent influenza vaccine vaccination strategy vaccine effectiveness

项目摘要

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.

项目摘要当前的流感疫苗提供了针对抗体介导的季节性流感菌株的保护包括在疫苗中。但是，它们不能防止共同循环不匹配的菌株，还有更多重要的是，未能保护可能导致潜在毁灭性大流行的抗原转变。该提案调查了T细胞免疫在个人和人口水平上的作用，在提供对多种流感菌株的广泛保护。动物和人类研究表明，T细胞可以提供应变转换保护，导致病毒清除率更快，免疫病理学降低和改善了临床结果，从而改善了诱导流感的保护水平的策略特定的T细胞至关重要。但是，关于增强流感特定的流感的规则知之甚少面对先前的流感的体液免疫，呼吸道中的常驻记忆T细胞中的居民记忆T细胞感染或疫苗接种。我们将使用多尺度的免疫流行学方法，将尺度从面对现有的感染和免疫力的动态和免疫力接受疫苗接种免疫力和感染在人群水平上的传播。该研究获得的知识将有助于指导未来的疫苗接种工作，以防止流感病毒更好地产生广泛的保护性T细胞免疫力在个人和整个人群中。