Does repeated influenza vaccination constrain influenza immune responses and protection?

重复接种流感疫苗是否会限制流感免疫反应和保护？

• 批准号: 10188306
• 负责人: Annette Fox
• 金额: $ 52.07万
• 依托单位: UNIVERSITY OF MELBOURNE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-03 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10188306
• 关键词: Adult; American; Antibodies; Antibody Response; Antibody titer measurement; Antigen-Antibody Complex; Attenuated; B-Lymphocytes; Benchmarking; Country; Data; Decision Making; Effectiveness; Elderly; Fostering; Goals; Health; Health Personnel; Hospitals; Immune response; Immunity; Immunologics; Immunology procedure; Individual; Infection; Influenza; Influenza Hemagglutinin; Influenza vaccination; Kinetics; Longitudinal Studies; Longitudinal cohort; Mathematics; Memory B-Lymphocyte; Mission; Modeling; Outcome; Patients; Persons; Policies; Population; Process; Process Measure; Public Health; Recording of previous events; Reporting; Research; Risk; Role; Seasons; Serological; Serum; Site; Statistical Models; Subgroup; Testing; United States National Institutes of Health; Update; Vaccinated; Vaccination; Vaccines; Virus; Work; adaptive immune response; cohort; cost; epidemiology study; evidence base; experience; immunogenicity; improved; influenza virus vaccine; innovation; insight; mathematical model; novel vaccines; program costs; programs; recruit; response; vaccine effectiveness

PROJECT SUMMARY/ABSTRACT Over 140 million Americans are among the more than 500 million people who receive influenza vaccines an- nually. An important subgroup are healthcare workers (HCWs) for whom vaccination is recommended, and sometimes mandated, to protect themselves and vulnerable patients from influenza infection. However, there have been no large, long term studies of HCWs to support the effectiveness of these policies. HCWs are now a highly vaccinated population, the effects of which are also poorly understood. Mounting evidence suggests an- tibody responses to vaccination can be attenuated with repeated vaccination, which is corroborated by reports of poor vaccine effectiveness among the repeatedly vaccinated. Thus, there is a compelling need to directly evaluate HCW vaccination programs. The long term goal is to improve the efficient and effective use of influ- enza vaccines. The objectives of this application are to understand the long-term consequences of repeated annual influenza vaccination among HCWs and to use statistical and mathematical modeling to elucidate the immunological processes that underlie vaccination responses and their implications for vaccination effective- ness. These objectives will be achieved by pursuing three specific aims: 1) To study the immunogenicity and effectiveness of influenza vaccination by prior vaccination experience; 2) To characterize immunological pro- files associated with vaccination and infection; and 3) To evaluate the impact of immunity on vaccination effec- tiveness. Under Aim 1, a cohort of hospital workers will be recruited and followed for up to 4 years to assess their pre- and post-vaccination and post-season antibody responses, and their risk of influenza infection. These outcomes will be compared by vaccination experience, classified as frequently vaccinated (received ≥3 vac- cines in the past 5 years), infrequently vaccinated (<3 vaccinations in past 5 years), vaccinated once, vaccine- naïve and unvaccinated. In Aim 2, intensive cellular and serological assessments will be conducted to dissect the influenza HA-reactive B cell and antibody response, and build antibody landscapes that typify the different vaccination groups. In Aim 3, the data generated in Aims 1 and 2 will be used to develop a mathematical mod- el that considers prior infection, vaccination history, antibody kinetics, and antigenic distance to understand the effects of repeated vaccination on vaccine effectiveness. This approach is innovative because it will provide insights into the effect of complex immunological dynamics on infection outcomes, thereby representing a nov- el departure from previous studies, which have ignored these difficult-to-measure processes. Completion of the proposed research will provide evidence to inform decisions about continued support for influenza vaccination programs among HCWs and general policies for annual influenza vaccination, as well as much-needed clarity about the effects of repeated vaccination.

项目摘要/摘要 超过1.4亿美国人是受到影响的超过5亿人之一。 一定一个重要的亚组是建议疫苗接种的医疗工作者（HCWS）， 有时会要求保护自己和脆弱的患者免受影响力的感染。但是，那里 对HCW的长期研究并不是支持这些政策的有效性。 HCW现在是 高度接种疫苗的人群，其影响也很少了解。越来越多的证据表明 可以通过重复疫苗接种来减弱触发接种的胫骨反应，这是通过报告证实的 反复接种疫苗的疫苗有效性不佳。那是一个迫切需要直接的 评估HCW疫苗接种计划。长期目标是提高影响力的有效和有效利用 - enza疫苗。该应用程序的目标是了解重复的长期后果 HCW中的年度影响力疫苗，并使用统计和数学建模来阐明 疫苗反应及其对疫苗有效疫苗的影响的免疫学过程 尼斯。这些目标将通过追求三个具体目标来实现：1）研究免疫原性和 通过先前的疫苗接种经验对影响力疫苗接种的有效性； 2）表征免疫学促进 与疫苗接种和感染相关的文件； 3）评估免疫对疫苗接种的影响有效 - 能态。在AIM 1下，将招募一批医院工作人员并最多遵循4年的评估 他们的疫苗接种和季后赛抗体反应以及影响力感染的风险。这些 结果将通过疫苗接种经验进行比较，分类为经常接种疫苗（接收≥3个VAC- Cines在过去的5年中），很少接种疫苗（过去5年中的<3次接种疫苗），一次接种一次，疫苗接种 - 在AIM 2中，将进行密集的细胞和血清学评估以剖析 影响力HA反应性B细胞和抗体反应，并建立抗体景观，代表不同的 疫苗接种组。在AIM 3中，AIMS 1和2中生成的数据将用于开发数学模式 EL认为先前感染，疫苗接种病史，抗体动力学和抗原距离 反复疫苗对疫苗有效性的影响。这种方法是创新的，因为它将提供 对复杂免疫动力学对感染结果的影响的见解，从而代表了11月 El偏离了以前的研究，这些研究忽略了这些难以估计的过程。完成 拟议的研究将提供证据，以告知有关持续支持影响力疫苗接种的决定。 HCWS和年度影响力疫苗接种的一般政策以及急需的清晰度 关于反复疫苗接种的影响。