Knowing whether vaccine protection wanes over time is important for health policy and drug development. However, quantifying waning effects is difficult. A simple contrast of vaccine efficacy at two different times compares different populations of individuals: those who were uninfected at the first time versus those who remain uninfected until the second time. Thus, the contrast of vaccine efficacy at early and late times can not be interpreted as a causal effect. We propose to quantify vaccine waning using the challenge effect, which is a contrast of outcomes under controlled exposures to the infectious agent following vaccination. We identify sharp bounds on the challenge effect under non-parametric assumptions that are broadly applicable in vaccine trials using routinely collected data. We demonstrate that the challenge effect can differ substantially from the conventional vaccine efficacy due to depletion of susceptible individuals from the risk set over time. Finally, we apply the methods to derive bounds on the waning of the BNT162b2 COVID-19 vaccine using data from a placebo-controlled randomized trial. Our estimates of the challenge effect suggest waning protection after 2 months beyond administration of the second vaccine dose.

翻译：了解疫苗保护效力是否随时间衰减对健康政策制定和药物研发至关重要。然而，量化衰减效应存在困难。简单比较两个不同时间点的疫苗效力时，所对比的是不同人群：第一时间点未受感染者与持续至第二时间点仍保持未感染状态的个体。因此，早期与晚期疫苗效力的对比不能解释为因果效应。我们提出采用挑战效应对疫苗衰减进行量化，即通过比较疫苗接种后受控暴露于病原体场景下的结局指标。基于非参数假设推导出挑战效应的锐界，该假设适用于常规收集数据的疫苗试验。研究表明，由于易感个体随时间从风险集中耗竭，挑战效应可能与常规疫苗效力存在显著差异。最终，我们采用安慰剂对照随机试验数据，将方法应用于界定BNT162b2新冠疫苗的衰减边界。挑战效应估计值表明，在第二剂疫苗接种后2个月保护效力出现衰减。