The "Dynamics of the immune responses to repeat influenza vaccination exposures" (DRIVE) Study

“重复接种流感疫苗后的免疫反应动态”(DRIVE) 研究

• 批准号: 10657605
• 负责人: BENJAMIN JOHN COWLING
• 金额: $ 123.51万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-11 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10657605
• 关键词: Adult; Affect; Age; Antibodies; Antibody Response; Antibody Specificity; Antibody titer measurement; Appearance; Attenuated; B-Lymphocytes; Binding; Biological Specimen Banks; Birth; Cells; Circulation; Complex; Coupled; Data; Development; Effectiveness; Epitopes; Evolution; Frequencies; Future; Genetic Transcription; Genotype; Hong Kong; Immune; Immune response; Immunity; Immunologic Memory; Immunologics; Individual; Infection; Influenza; Influenza vaccination; Injections; Intervention; Measures; Modeling; Nose; Observational Study; Participant; Pattern; Persons; Phenotype; Placebos; Population; Predisposition; Process; Proxy; Public Health; Randomized; Recommendation; Recording of previous events; Research; Residual state; Reverse Transcriptase Polymerase Chain Reaction; Saline; Sampling; Serum; Shapes; Specificity; Specimen; Statistical Models; T cell response; Testing; Time; Vaccinated; Vaccination; Vaccinee; Vaccines; design; high dimensionality; immunogenicity; immunological status; imprint; improved; influenza infection; influenza virus vaccine; insight; nasal swab; predictive modeling; primary endpoint; randomized, clinical trials; response; seasonal influenza; secondary endpoint; standard measure; theories; universal vaccine; vaccination strategy; vaccine effectiveness; vaccine efficacy; vaccine failure; vaccine response

PROJECT SUMMARY Annual vaccination remains the primary public health strategy to mitigate the burden of influenza infection, and there is evidence that repeated influenza vaccination can affect the efficacy of the vaccine. This evidence arises not only from multiple observational studies of vaccine effectiveness but also studies of immunogenicity, including small trials. Understanding what causes influenza vaccines to be more or less effective in different people and populations is critical to the rational deployment of existing vaccines and the development of universal vaccines. But the causes of altered effectiveness and immunogenicity in repeat vaccinees are intrinsically difficult to study in populations in which vaccination is universally recommended, because repeat vaccinees differ from other vaccinees and non-vaccinees in important ways. These differences leave open the possibility of residual confounding in infection and vaccination history, and thus make it difficult to identify the effects of vaccination itself. We propose a randomized, clinical trial to investigate the effects of repeat vaccination and their underlying immunological causes in an adult population with low vaccination coverage and no recommendation for influenza vaccination. Approximately 820 adults in Hong Kong will be randomized into five groups, with one group vaccinated the first year, and other groups receiving placebo (saline) injections; each year, another group will start receiving the influenza vaccine, and will be vaccinated annually until the study ends after four years. This design will allow comparison of vaccine responses and failures (infections) in the placebo, newly vaccinated, and repeatedly vaccinated participants. Additionally, it will provide longitudinal samples of immune status and influenza-specific responses over time, from which we will develop predictive models of the response to vaccination and infection, including repeat vaccination. The proposed high-dimensional immunological profiling, coupled with statistical approaches that can accommodate the complexity of the key hypotheses, should maximize insight into the effects of repeated vaccination on seasonal influenza. The models will formalize, evaluate, and extend current theory, and thus provide a quantitative basis for anticipating vaccine non- responsiveness and improving vaccination strategies. Banked specimens will enable new hypotheses to be tested in the future.

项目摘要 年度疫苗接种仍然是减轻流感感染负担的主要公共卫生战略， 有证据表明，反复的流感疫苗接种会影响疫苗的功效。这一证据出现了 不仅来自疫苗有效性的多项观察性研究，而且还来自免疫原性的研究 包括小型试验。了解什么导致流感疫苗或多或少在不同的地方有效 人们和人口对于合理的现有疫苗和普遍的发展至关重要 疫苗。但是重复疫苗的有效性和免疫原性改变的原因在本质上是困难的 在普遍推荐的疫苗接种的种群中研究，因为重复疫苗与 其他疫苗和非vaccinees的重要方式。这些差异使剩余的可能性开放 在感染和疫苗接种病史中混淆，因此很难识别疫苗接种的影响 本身。我们提出了一项随机的临床试验，以研究重复疫苗接种及其基础的影响 疫苗接种范围低的成年人口中的免疫学原因，不建议流感 疫苗接种。香港大约有820名成年人将被随机分为五组，其中一组 第一年接种了疫苗，其他接受安慰剂（盐水）注射的小组；每年，另一组将 开始接受流感疫苗，并将每年接种疫苗，直到研究在四年后结束。这 设计将允许在安慰剂中比较疫苗的反应和失败（感染），新近接种疫苗， 并反复接种疫苗的参与者。此外，它将提供免疫状态的纵向样本和 随着时间的推移，流感特定的反应，我们将从中开发出对响应的预测模型 疫苗接种和感染，包括重复疫苗接种。拟议的高维免疫学分析， 再加上可以适应关键假设复杂性的统计方法，应 最大程度地了解反复疫苗接种对季节性流感的影响。模型将正式化， 评估和扩展当前理论，因此为预期疫苗非 - 提供了定量基础 响应能力和改善疫苗接种策略。银行标本将使新的假设成为 将来经过测试。