Impact of repeated vaccination on the effectiveness of seasonal influenza vaccines

重复接种对季节性流感疫苗效果的影响 摘要 流感病毒引起大流行和季节性暴发，导致数千至数百万人死亡 人类的生命。接种疫苗是预防流感暴发并将其影响降至最低的最佳选择 健康。在美国，自2010年以来，建议每年接种流感疫苗6 几个月大或更大。然而，疫苗的性能在流感季节之间差异很大，而且 已经观察到疫苗效力降低。研究报告称，在两年内接种疫苗的人 连续的流感季节在第二个季节的疫苗效力低于 在上一季没有接种疫苗。这些发现引起了人们的深刻困惑 公众对每年接种流感疫苗的潜在好处的看法。因此，迫切需要解决 重复接种疫苗相关的既有免疫对流感疫苗性能的影响。 该项目的目标是表征反复接种流感疫苗对特异性的影响。 以及交叉反应抗体的大小和季节性流感疫苗的效力。二 提出了具体的目标：1)确定体液的特异性、大小和纵向模式 人类对重复接种季节性疫苗的反应，以及2)测试重复接种疫苗的效果- 相关预先存在的免疫力对雪貂流感疫苗性能的影响。 通过比较反复接种流感疫苗和不接种流感疫苗的人群的抗体，我们希望显示 是否以及如何通过反复接种流感疫苗获得预先存在的免疫力影响特异性 以及由此产生的抗体的交叉反应的大小，从而影响疫苗的有效性。从我们的 在雪貂身上的研究，我们希望显示重复接种疫苗前相关的变异是否以及如何 现有的免疫力影响流感疫苗的性能。这项研究将扩大我们对分子的理解 可能影响重复接种疫苗如何影响流感疫苗效果的机制。因此，这一点 研究将为评估每年接种流感疫苗的需要和优化提供基本知识 流感疫苗性能。

Impact of repeated vaccination on the effectiveness of seasonal influenza vaccines Summary Influenza viruses cause pandemic and seasonal outbreaks that lead to the loss of thousands to millions of human lives. Vaccination is the best option for preventing influenza outbreaks and minimizing their effects on health. In the United States, annual influenza vaccination has been recommended since 2010 for persons 6 months of age and older. However, vaccine performance varies significantly between influenza seasons, and reduced vaccine effectiveness has been observed. Studies have reported that persons vaccinated during two consecutive influenza seasons had lower vaccine effectiveness during the second season than persons who had not been vaccinated during the prior season. These findings have caused profound confusion among the public regarding the potential benefit of annual influenza vaccination. Thus, there is a critical need to address the effect of repeated vaccination–associated pre-existing immunity on influenza vaccine performance. The objective of this project is to characterize the effects of repeated influenza vaccination on the specificity and magnitude of cross-reactive antibodies and on the effectiveness of seasonal influenza vaccines. Two specific aims are proposed: 1) determine the specificity, magnitude, and longitudinal patterns of humoral responses in humans with repeated seasonal vaccination, and 2) test the effect of repeated vaccination– associated pre-existing immunity on influenza vaccine performance in ferrets. By comparing antibodies in persons with and without repeated influenza vaccination, we expect to show whether and how pre-existing immunity achieved through repeated influenza vaccination affects the specificity and magnitude of the cross-reactivity for the resulting antibodies and, thus, vaccine effectiveness. From our studies in ferrets, we expect to show whether and how variations in repeated vaccination–associated pre- existing immunity affect influenza vaccine performance. This study will expand our understanding of molecular mechanisms that may influence how repeated vaccination affects influenza vaccine performance. Thus, this study will provide basic knowledge for evaluating the need for annual influenza vaccination and for optimizing influenza vaccine performance.