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

项目总结 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，以及 有证据表明，反复接种流感疫苗会影响疫苗的效果。这一证据来自于 不仅从疫苗有效性的多个观察性研究，而且从免疫原性的研究， 包括小规模的试验。了解是什么导致流感疫苗在不同的地方或多或少有效 人和人口是合理部署现有疫苗和发展普及疫苗的关键 疫苗。但是，重复接种疫苗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，因为重复接种的人不同于 其他接种疫苗者和非接种者在重要方面。这些差异留下了剩余的可能性 感染和疫苗接种史混淆，因此很难确定疫苗接种的效果 它本身。我们建议进行一项随机的临床试验，以调查重复接种疫苗的效果及其潜在的影响。 接种覆盖率低且未推荐接种流感的成人人群的免疫学原因 接种疫苗。约820名香港成年人将被随机分成五组，每组一组 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，每年接种一次，直到四年后研究结束。这 设计将允许比较新接种的安慰剂的疫苗反应和失败(感染)， 并反复为参与者接种疫苗。此外，它还将提供免疫状态的纵向样本和 随着时间的推移，流感的特异性反应，我们将根据这些反应开发预测模型 接种疫苗和感染，包括重复接种疫苗。拟议的高维免疫图谱， 再加上能够适应关键假设的复杂性的统计方法，应该 最大限度地深入了解重复接种疫苗对季节性流感的影响。模型将被形式化， 评估和扩展现有理论，从而为预测非疫苗提供定量依据 提高反应能力和改进疫苗接种战略。储存的标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.