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

项目概要 每年接种疫苗仍然是减轻流感感染负担的主要公共卫生策略，并且 有证据表明，重复接种流感疫苗会影响疫苗的功效。这个证据出现了 不仅来自疫苗有效性的多项观察性研究，还来自免疫原性研究， 包括小试验。了解导致流感疫苗在不同情况下或多或少有效的原因 人和人群对于合理部署现有疫苗和开发通用疫苗至关重要 疫苗。但重复疫苗接种者的有效性和免疫原性改变的原因本质上是困难的 在普遍建议接种疫苗的人群中进行研究，因为重复接种者与重复接种者不同 其他疫苗接种者和非疫苗接种者以重要方式。这些差异留下了残留的可能性 感染和疫苗接种史混杂，从而难以确定疫苗接种的效果 本身。我们提出一项随机临床试验来调查重复接种疫苗的效果及其潜在的影响 疫苗接种覆盖率低且不建议接种流感的成年人群中的免疫原因 疫苗接种。香港约820名成年人将被随机分为五组，其中一组 第一年接种疫苗，其他组接受安慰剂（盐水）注射；每年，另一个小组将 开始接种流感疫苗，并将每年接种一次，直到四年后研究结束。这个 设计将允许比较安慰剂、新接种疫苗、 并反复为参与者接种疫苗。此外，它将提供免疫状态的纵向样本和 随着时间的推移，流感特异性反应，我们将据此开发反应的预测模型 疫苗接种和感染，包括重复疫苗接种。所提出的高维免疫学分析， 结合可以适应关键假设复杂性的统计方法，应该 最大限度地了解重复接种疫苗对季节性流感的影响。模型将正式化， 评估并扩展现有理论，从而为预测疫苗非预期提供定量基础 反应和改进疫苗接种策略。储存的样本将使新的假设成为可能 在未来进行测试。

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.