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

项目摘要 每年接种疫苗仍然是减轻流感感染负担的主要公共卫生战略， 有证据显示，多次接种流感疫苗会影响疫苗的效力。这一证据表明， 不仅来自疫苗有效性的多项观察性研究，而且来自免疫原性研究， 包括小型试验。了解是什么原因导致流感疫苗在不同地区或多或少有效 对合理部署现有疫苗和发展普及疫苗至关重要， 疫苗。但是重复接种者的效力和免疫原性改变的原因本质上是困难的 在普遍推荐接种疫苗的人群中进行研究，因为重复接种者与 其他疫苗接种者和非疫苗接种者。这些差异留下了残留的可能性 感染和疫苗接种史混杂，因此难以确定疫苗接种的效果 本身我们建议进行一项随机临床试验，以调查重复接种疫苗的效果及其潜在的 免疫原因在成人人群中的低疫苗接种覆盖率和没有流感的建议 预防针香港约820名成年人将被随机分为五组， 第一年接种疫苗，其他组接受安慰剂（生理盐水）注射;每年，另一组将 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 设计将允许比较安慰剂，新接种疫苗， 并反复接种疫苗。此外，它将提供免疫状态的纵向样本， 流感特异性反应随时间的变化，从中我们将开发出反应的预测模型， 接种疫苗和感染，包括重复接种。所提出的高维免疫学分析， 再加上能够适应关键假设复杂性的统计方法， 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， 评估和扩展当前的理论，从而为预测疫苗非免疫性提供定量基础。 提高免疫力和改进疫苗接种策略。库存标本将使新的假设， 测试在未来。

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.