Like the mechanisms of action as adjuvants, the pharmacodynamics of injected forms of aluminum commonly used in vaccines are not well-characterized, particularly with respect to how differences in schedules impact accumulation and how factors such as genetics and environmental influences on detoxification influence clearance. Previous modeling efforts are based on very little empirical data, with the model by Priest based on whole-body clearance rates estimated from a study involving a single human subject. In this analysis, we explore the expected acute exposures and longer-term whole-body accumulation/clearance across three vaccination schedules: the current US Centers for Disease Control and Prevention (CDC) schedule, the current CDC schedule using low aluminum or no aluminum vaccines, and Dr. Paul Thomas' "Vaccine Friendly Plan" schedule. We then study the effects of an implicit assumption of the Priest model on whether clearance dynamics from successive doses are influenced by the current level of aluminum or modeled by the assumption that a new dose has its own whole-body dynamics "reset" on the day of injection. We model two additional factors: variation (deficiency) in aluminum detoxification, and a factor added to the Priest equation to model the potential impact of aluminum itself on cellular and whole-body detoxification. These explorations are compared to a previously estimated pediatric dose limit (PDL) of whole-body aluminum exposure and provide a new statistic: %alumTox, the (expected) percentage of days (or weeks) an infant is in aluminum toxicity, reflecting chronic toxicity. We show that among three schedules, the CDC schedule results in the highest %alumTox regardless of model assumptions, and the Vaccine Friendly Plan schedule, which avoids >1 ACV per office visit results in the lowest (expected) %alumTox. These results are conservative, as the MSL is derived from data used by FDA to estimate safety of aluminum in adult humans. These results demonstrate high potential utility of modeling variation in patient responses to aluminum. More empirical data from individuals who are suspected of being intolerant of aluminum from vaccines, evidenced by high aluminum retention, neurodevelopmental disorders and/or a myriad of chronic illnesses would help answer questions on whether the model predictions can be used to estimate parameter values tied to genetic factors including genomic sequence variation and family history of chronic illnesses tied to aluminum exposure.

中文翻译：

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三种疫苗接种方案中铝的急性暴露和长期滞留以及遗传和环境变异的影响。

与佐剂的作用机制一样，疫苗中常用的铝注射剂的药效学也没有很好的特征，特别是在日程安排差异如何影响累积以及遗传学和环境因素对排毒的影响等方面如何影响清除率。先前的建模工作是基于很少的经验数据，而Priest的模型是基于一项涉及单个人类受试者的研究估计的全身清除率。在此分析中，我们探讨了三种疫苗接种计划的预期急性暴露和长期的全身积累/清除：当前的美国疾病控制与预防中心（CDC）计划，当前使用低铝或无铝疫苗的CDC计划以及保罗·托马斯（Paul Thomas）的“疫苗友好计划” 日程。然后，我们研究了Priest模型的隐式假设对连续剂量清除动态的影响是否受到当前铝水平的影响，还是通过新剂量当天具有其自身全身动态“重置”的假设进行建模注射。我们对两个附加因素进行建模：铝排毒的变化（缺陷），以及添加到Priest方程中的一个因素，以模拟铝本身对细胞和全身排毒的潜在影响。将这些研究结果与先前估计的全身铝暴露的儿科剂量限值（PDL）进行了比较，并提供了新的统计数据：％alumTox，即婴儿铝毒性的天数（或周数）（预期）百分比，反映出慢性毒性。我们显示在三个时间表中，无论模型假设如何，CDC计划产生的％alumTox最高，而疫苗友好计划计划则避免了每次就诊的> 1 ACV，从而导致了最低（预期）％alumTox。这些结果是保守的，因为MSL来自FDA用来估计成人铝的安全性的数据。这些结果表明，对患者对铝的反应变化进行建模具有很高的潜在实用性。来自怀疑对疫苗中的铝不耐性的个体的更多经验数据，以较高的铝保留量为证，